Updated on 2025/08/16

写真a

 
TAKIGAWA Masaharu
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Special-Appointment Professor
Position
Special-Appointment Professor
Homepage
http://www.dent.okayama-u.ac.jp/arcocs/
External link

Degree

  • (BLANK) D.D.S., Ph.D. ( Osaka University )

Research Interests

  • CCNファミリー

  • CCNタンパク質

  • CCN family protein

  • Cartilage

  • 軟骨

  • 成長因子

  • Bone

  • Angiogenesis

  • 骨

  • 血管新生

  • 石灰化組織

  • Calcified-tissue

  • Growth factor

  • アンチエイジング

  • 構造生物学

Research Areas

  • Life Science / Oral biological science

  • Life Science / Medical biochemistry

  • Life Science / Nutrition science and health science

Education

  • Osaka University   歯学研究科   歯学基礎系生化学

    1973 - 1977

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    Country： Japan

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  • Osaka University   歯学部   歯学科

    1967 - 1973

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    Country： Japan

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Research History

  • 岡山大学 学術研究院医歯薬学域   教授（副センター長）

    2021.4

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  • Okayama University   Graduate School of Medicine , Dentistry and Pharmaceutical Sciences

    2019.4 - 2021.3

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  • Okayama University   Professor Emeritus

    2014

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  • Okayama University   Graduate School of Medicine , Dentistry and Pharmaceutical Sciences

    2014 - 2019

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  • 日本学術会議連携会員

    2011 - 2017

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  • Okayama University

    2006 - 2008

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  • Okayama University   Graduate School of Medicine , Dentistry and Pharmaceutical Sciences   Professor

    2005 - 2014

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  • - Professor,School of Dentistry,Dental School,Okayama University

    2005

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  • - Professor,Science of Functional Recovery and Reconstruction,Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,Okayama University

    2005

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  • Okayama University   大学院医歯学総合研究科 口腔生化・分子歯科学   Professor

    2001 - 2005

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  • Okayama University

    2000 - 2002

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  • Professor,School of Dentistry,Dental School,Okayama University

    1994 - 2005

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  • Okayama University   Dental School   Professor

    1994 - 2001

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  • Associate Professor, Osaka University Dental School

    1991 - 1994

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  • Osaka University   School of Dentistry   Associate Professor (as old post name)

    1991 - 1994

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  • Senior Assistant Professor,1981-1991 Assitant Professor, Osaka University Dental School

    1981 - 1991

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  • Osaka University   School of Dentistry   Lecturer

    1981 - 1991

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  • 米国ウイスコンシン大学   博士研究員

    1980 - 1982

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  • Researcher,University of Wisconsin

    1980 - 1982

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  • Osaka University   School of Dentistry   Research Assistant

    1977 - 1981

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Professional Memberships

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Committee Memberships

  • 日本CCNファミリー研究会   代表世話人  

    2007   

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    Committee type：Academic society

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  • International CCN Society   副会長->学術担当理事長->学術委員会長  

    2004   

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    Committee type：Academic society

    International CCN Society

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  • 日本血管生物医学会   評議員  

    2003   

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    Committee type：Academic society

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  • 日本結合組織学会   評議員  

    1997   

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    Committee type：Academic society

    日本結合組織学会

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  • 日本軟骨代謝学会   理事−＞監事->名誉会員  

    1997   

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    Committee type：Academic society

    日本軟骨代謝学会

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  • 日本再生医療学会(前身の日本組織工学会以来）   評議員  

    1995 - 2014   

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    Committee type：Academic society

    日本再生医療学会

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  • 日本生化学会   評議員  

    1994   

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    Committee type：Academic society

    日本生化学会

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  • 岡山歯学会   理事,元会長  

    1994 - 2014   

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    Committee type：Academic society

    岡山歯学会

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  • 歯科基礎医学会   評議員−＞理事−＞評議員  

    1992   

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    Committee type：Academic society

    歯科基礎医学会

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  • 日本骨代謝学会   評議員−＞理事−＞評議員  

    1984   

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    Committee type：Academic society

    日本骨代謝学会

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  • 大阪大学歯学会   元庶務理事  

       

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    Committee type：Academic society

    大阪大学歯学会

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Papers

  • Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors Reviewed International journal

    Loc Dinh Hoang, Eriko Aoyama, Miki Hiasa, Hiroshi Omote, Satoshi Kubota, Takuo Kuboki, Masaharu Takigawa

    International Journal of Molecular Sciences   24 ( 24 )   17294 - 17294   2023.12

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    Authorship：Last author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes.

    DOI： 10.3390/ijms242417294

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  • Expression and function of CCN2-derived circRNAs in chondrocytes Reviewed

    Soma Kato, Kazumi Kawata, Takashi Nishida, Tomomi Mizukawa, Masaharu Takigawa, Seiji Iida, Satoshi Kubota

    Journal of Cell Communication and Signaling   2023.9

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    Abstract

    Cellular communication network factor 2 (CCN2) molecules promote endochondral ossification and articular cartilage regeneration, and circular RNAs (circRNAs), which arise from various genes and regulate gene expression by adsorbing miRNAs, are known to be synthesized from CCN2 in human vascular endothelial cells and other types of cells. However, in chondrocytes, not only the function but also the presence of CCN2-derived circRNA remains completely unknown. In the present study, we investigated the expression and function of CCN2-derived circRNAs in chondrocytes. Amplicons smaller than those from known CCN2-derived circRNAs were observed using RT-PCR analysis that could specifically amplify CCN2-derived circRNAs in human chondrocytic HCS-2/8 cells. The nucleotide sequences of the PCR products indicated novel circRNAs in the HCS-2/8 cells that were different from known CCN2-derived circRNAs. Moreover, the expression of several Ccn2-derived circRNAs in murine chondroblastic ATDC5 cells was confirmed and observed to change alongside chondrocytic differentiation. Next, one of these circRNAs was knocked down in HCS-2/8 cells to investigate the function of the human CCN2-derived circRNA. As a result, CCN2-derived circRNA knockdown significantly reduced the expression of aggrecan mRNA and proteoglycan synthesis. Our data suggest that CCN2-derived circRNAs are expressed in chondrocytes and play a role in chondrogenic differentiation.

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    DOI： 10.1007/s12079-023-00782-7

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    Other Link： https://link.springer.com/article/10.1007/s12079-023-00782-7/fulltext.html

  • Dual roles of cellular communication network factor 6 (CCN6) in the invasion and metastasis of oral cancer cells to bone via binding to BMP2 and RANKL Reviewed

    Hiroaki Hochi, Satoshi Kubota, Masaharu Takigawa, Takashi Nishida

    Carcinogenesis   2023.8

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    Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

    Abstract

    The acquisition of motility via epithelial–mesenchymal transition (EMT) and osteoclast induction are essential for the invasion and metastasis of oral squamous cell carcinoma (OSCC) to bone. However, the molecule suppressing both EMT and osteoclastogenesis is still unknown. In this study, we found that cellular communication network factor 6 (CCN6) was less produced in a human OSCC cell line, HSC-3 with mesenchymal phenotype, than in HSC-2 cells without it. Notably, CCN6 interacted with bone morphogenetic protein 2 (BMP2) and suppressed the cell migration of HSC-3 cells stimulated by BMP2. Moreover, knockdown of CCN6 in HSC-2 cells led to the promotion of EMT and enhanced the effect of transforming growth factor-β (TGF-β) on the promotion of EMT. Furthermore, CCN6 combined with BMP2 suppressed EMT. These results suggest that CCN6 strongly suppresses EMT in cooperation with BMP2 and TGF-β. Interestingly, CCN6 combined with BMP2 increased the gene expression of receptor activator of nuclear factor-κB ligand (RANKL) in HSC-2 and HSC-3 cells. Additionally, CCN6 interacted with RANKL, and CCN6 combined with RANKL suppressed RANKL-induced osteoclast formation. In metastatic lesions, increasing BMP2 due to the bone destruction led to interference with binding of CCN6 to RANKL, which results in the promotion of bone metastasis of OSCC cells due to continuous osteoclastogenesis. These findings suggest that CCN6 plays dual roles in the suppression of EMT and in the promotion of bone destruction of OSCC in primary and metastatic lesions, respectively, through cooperation with BMP2 and interference with RANKL.

    DOI： 10.1093/carcin/bgad057

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  • 軟骨細胞におけるCCN2由来circRNAの発現および機能の探索

    加藤 壮真, 河田 かずみ, 西田 崇, 水川 朋美, 滝川 正春, 飯田 征二, 久保田 聡

    日本骨代謝学会学術集会プログラム抄録集   41回   149 - 149   2023.7

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    Language：Japanese   Publisher：(一社)日本骨代謝学会  

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  • Do not overwork: cellular communication network factor 3 for life in cartilage. Reviewed International journal

    Satoshi Kubota, Harumi Kawaki, Bernard Perbal, Masaharu Takigawa, Kazumi Kawata, Takako Hattori, Takashi Nishida

    Journal of cell communication and signaling   17 ( 2 )   353 - 359   2023.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    Cellular communication network factor (CCN) 3, which is one of the founding members of the CCN family, displays diverse functions. However, this protein generally represses the proliferation of a variety of cells. Along with skeletal development, CCN3 is produced in cartilaginous anlagen, growth plate cartilage and epiphysial cartilage. Interestingly, CCN3 is drastically induced in the growth plates of mice lacking CCN2, which promotes endochondral ossification. Notably, chondrocytes in these mutant mice with elevated CCN3 production also suffer from impaired glycolysis and energy metabolism, suggesting a critical role of CCN3 in cartilage metabolism. Recently, CCN3 was found to be strongly induced by impaired glycolysis, and in our study, we located an enhancer that mediated CCN3 regulation via starvation. Subsequent investigations specified regulatory factor binding to the X-box 1 (RFX1) as a transcription factor mediating this CCN3 regulation. Impaired glycolysis is a serious problem, resulting in an energy shortage in cartilage without vasculature. CCN3 produced under such starved conditions restricts energy consumption by repressing cell proliferation, leading chondrocytes to quiescence and survival. This CCN3 regulatory system is indicated to play an important role in articular cartilage maintenance, as well as in skeletal development. Furthermore, CCN3 continues to regulate cartilage metabolism even during the aging process, probably utilizing this regulatory system. Altogether, CCN3 seems to prevent "overwork" by chondrocytes to ensure their sustainable life in cartilage by sensing energy metabolism. Similar roles are suspected to exist in relation to systemic metabolism, since CCN3 is found in the bloodstream.

    DOI： 10.1007/s12079-023-00723-4

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  • Angiogenesis Assays for the Analysis of CCN Proteins Invited Reviewed International journal

    Tsuyoshi Shimo, Mari Shimatani, Akihiko Tanimura, Masaharu Takigawa

    Methods in Molecular Biology   2582   295 - 308   2023

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    Authorship：Last author   Language：English   Publishing type：Part of collection (book)  

    Angiogenesis, the process of generating new blood vessels from an existing vasculature, is essential in normal developmental processes such as endochondral ossification and in numerous kinds of pathogenesis including tumor growth. A part from the actin of angiogenic factor or antiangiogenic factor, it is still unknown at which stage of the angiogenic cascade these agents affect angiogenesis. Here, we describe methods for the use of cellular communication network factor/connective tissue growth factor (CTGF/CCN2) and CCN2-neutralizing antibody in the currently used principal angiogenesis assays, including those in vitro ones for the proliferation, migration, adhesion, and tube formation of endothelial cells and in vivo assays such as those utilizing type I collagen implantation and the chick chorioallantoic membrane (CAM). In addition, we introduce an autofluorescence imaging of blood vessels in the subcutaneous tumor xenograft mouse model. These assays can be applied to studies on roles of CCN proteins in tumor metastasis and development of treatment strategies targeting CCN proteins.

    DOI： 10.1007/978-1-0716-2744-0_20

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  • Protocols for Screening Peptides Binding to CCN Family 2 Proteins and Their Extended Utility Invited Reviewed International journal

    Satoshi Kubota, Harumi Kawaki, Masaharu Takigawa

    Methods in Molecular Biology   2582   87 - 101   2023

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    Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

    The function of CCN family proteins is determined by their interactions with multiple cofactors that are present in the microenvironment. Therefore, determining these cofactors is critically important in understanding the molecular function of CCN family members. For this objective, a bacteriophage random peptide display library is a suitable tool. In this library, each filamentous bacteriophage is designed to display an oligopeptide of 7-20 random amino acid residues on its surface. Bacteriophage clones that possess peptides that bind to a CCN family protein are selected through several cycles of a process called biopanning or affinity selection. By determining the nucleotide sequence of the DNA that encodes the displayed peptide, the oligopeptides that specifically bind to the CCN family member can be specified. The obtained peptide sequences can be utilized to design peptide aptamers for CCN family proteins, or as a key sequence to determine new CCN family cofactor candidates in silico. Instead of a random peptide cDNA library, an antibody cDNA library from naïve lymphocytes or from B cells immunized by a CCN family protein can be used in order to obtain a highly specific CCN family detection or functional modulation tool.

    DOI： 10.1007/978-1-0716-2744-0_8

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  • Evaluation of the Molecular Interaction Between CCN 2 Protein and Its Binding Partners: A Solid-Phase Binding 3 Assay and Surface Plasmon Resonance Invited Reviewed

    Eriko Aoyama, Masaharu Takigawa

    Methods in Molecular Biology   2582   77 - 86   2023

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    DOI： 10.1007/978-1-0716-2744-0_7

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  • Imaging of Molecular Interaction Between CCN Protein 2 and Its Binding Partners: An In Situ Proximity Ligation 3 Assay of Interaction Between CCN2 and Rab14 4 in Chondrocytes Reviewed International journal

    Mitsuhiro Hoshijima, Eriko Aoyama, Hiroshi Kamioka, Masaharu Takigawa

    Methods in Molecular Biology   2582   31 - 37   2023

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    Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

    An in situ proximity ligation assay (PLA) enables visualization of protein interactions in fixed cells. It is a powerful method for investigating protein-protein binding of endogenously expressed proteins. To confirm binding between CCN2 and Rab14 GTPase (Rab14) in chondrocytes, we performed a PLA using chondrocytic HCS-2/8 cells. The protocol in this chapter introduces an optimized technique for visualizing intracellular interactions of CCN2 and Rab14 in fixed cells using a PLA.

    DOI： 10.1007/978-1-0716-2744-0_4

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  • Cellular Fluorescence Imaging for the Evaluation 2 of Bioactivity of CCN Family Proteins Reviewed International journal

    Harumi Kawaki, Satoshi Kubota, Masaharu Takigawa

    Methods in Molecular Biology   2582   23 - 29   2023

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    Authorship：Last author   Language：English   Publishing type：Part of collection (book)  

    The method of labeling proteins of interest with fluorescent dyes that can specifically stain organelles in living cells provides a tool for investigating various cellular processes under a microscope. Visualization (imaging) of the cells using fluorescence has many advantages, including the ability to stain multiple cell organelles and intracellular proteins simultaneously and discriminately, and is used in many research fields. In this chapter, we describe the observation of cell organelles using fluorescence staining to analyze the functions of CCN family proteins involved in various cellular events.

    DOI： 10.1007/978-1-0716-2744-0_3

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  • Novel Cell Biological Assays for Measuring Bone 2 Remodeling Activities of CCN Proteins International journal

    Takashi Nishida, Satoshi Kubota, Masaharu Takigawa

    Methods in molecular biology (Clifton, N.J.)   2582   255 - 268   2023

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    Although two-dimensional (2D) cultures from bone lineage cells are often used, it is well-known that this culture system is completely different from the in vivo bone matrix environment. In this paper, we describe a 3D culture method using both the mouse osteocytic cell line, MLO-Y4, and an osteocyte-enriched population of the cells isolated from mice. These cells are embedded in collagen gel with recombinant cellular communication network (CCN) factor proteins; then, osteoblasts or osteoclasts are inoculated and cultured on the collagen gel. Because this method mimics the in vitro bone matrix environment, it is useful for understanding the detailed mechanism of actions of CCN proteins in the bone matrix.

    DOI： 10.1007/978-1-0716-2744-0_17

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  • The Evaluation of Meniscus Regenerative Effects 2 of LIPUS-Induced CCN Proteins: Induction by LIPUS of CCN2 3 and Meniscus-Related Genes in Cultured Meniscus Cells 4 and Meniscus Tissues

    Yusuke Kamatsuki, Eriko Aoyama, Takayuki Furumatsu, Toshifumi Ozaki, Masaharu Takigawa

    Methods in Molecular Biology   2582   223 - 235   2023

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    Authorship：Last author,　Corresponding author   Publishing type：Part of collection (book)   Publisher：Springer US  

    DOI： 10.1007/978-1-0716-2744-0_15

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  • Analyses of the Posttranscriptional Regulation of CCN 2 Genes: Approach to Multiple Steps of CCN2 Gene Expression Invited Reviewed International journal

    Seiji Kondo, Satoshi Kubota, Masaharu Takigawa

    Methods in Molecular Biology   2582   127 - 155   2023

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    Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

    Cells generally control the concentration of mRNA via transcriptional and posttranscriptional regulation, so the separate contributions of synthesis and degradation (decay) cannot be discriminated by the quantification of mRNA. To elucidate the contribution of posttranscriptional regulation, all experimental procedures for the analysis of the total transcript level, transcriptional induction, degradation of the target mRNA, and inhibition of mRNA translation are performed either individually or in combination. From our experience, measurement of the steady-state levels of mRNA using quantitative real-time polymerase chain reaction is an essential first step in quantifying the ccn2 gene expression. Subsequently, the effect of transcription rates should be assessed by reporter assays of the ccn2 promoter and nuclear run-on assays. The stability of ccn2 mRNAs is then evaluated in the presence of a metabolic inhibitor actinomycin D, followed by mRNA degradation assays in vitro. Finally, repression of ccn2 mRNA translation can be estimated by comparing the expression of mRNA and protein changes. We herein report the strategic methods used in a series of analyses to elucidate the possible involvement of the posttranscriptional regulatory mechanism of the ccn2 gene and show how this approach can, in theory, be used to elucidate the posttranscriptional regulation of other genes belonging to the CCN family.

    DOI： 10.1007/978-1-0716-2744-0_10

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  • CCN Proteins (Cellular Communication Network Factors): Expanding Their Repertoire Toward a New Concept Invited Reviewed

    Masaharu Takigawa

    Methods in Molecular Biology   2582   1 - 10   2023

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  • Mouse Models of Tumor Bone Metastasis and Invasion 2 for Studying CCN Proteins Invited Reviewed International journal

    Tsuyoshi Shimo, Tatsuo Okui, Naohiro Horie, Kenji Yokozeki, Masaharu Takigawa, Akira Sasaki

    Methods in Molecular Biology   2582   295 - 308   2023

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    Language：English   Publishing type：Part of collection (book)  

    Bone metastasis and bone destruction are common occurrences in human malignancies, including breast, prostate, and lung cancer, and are associated with a high morbidity rate because of intractable bone pain, pathological fractures, hypercalcemia, and nerve compression. Animal models of bone metastasis and bone destruction are important tools to investigate the pathogenesis and develop treatment strategies. However, there are few models of spontaneous bone metastasis despite the fact that animals often spontaneously develop cancer. Here, we describe methods for developing a mouse model of breast cancer bone metastasis achieved by injection of MDA-MB-231 breast cancer cells into the left cardiac ventricle. In addition, we introduce mouse model of the bone destruction by injection of SAS oral squamous cell carcinoma cells into the bone marrow space of the right tibial metaphysis. These assays can be applied to studies on roles of cellular communication network factor/connective tissue growth factor (CTGF/CCN2) protein in tumor metastasis and development of treatment strategies targeting CCN proteins.

    DOI： 10.1007/978-1-0716-2744-0_24

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  • Elevated Expression of CCN3 in Articular Cartilage Induces Osteoarthritis in Hip Joints Irrespective of Age and Weight Bearing. Reviewed International journal

    Kazuki Hirose, Miho Kuwahara, Eiji Nakata, Tomonori Tetsunaga, Kazuki Yamada, Kenta Saiga, Masaharu Takigawa, Toshifumi Ozaki, Satoshi Kubota, Takako Hattori

    International journal of molecular sciences   23 ( 23 )   2022.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    Osteoarthritis (OA) occurs not only in the knee but also in peripheral joints throughout the whole body. Previously, we have shown that the expression of cellular communication network factor 3 (CCN3), a matricellular protein, increases with age in knee articular cartilage, and the misexpression of CCN3 in cartilage induces senescence-associated secretory phenotype (SASP) factors, indicating that CCN3 promotes cartilage senescence. Here, we investigated the correlation between CCN3 expression and OA degenerative changes, principally in human femoral head cartilage. Human femoral heads obtained from patients who received total hip arthroplasty were categorized into OA and femoral neck fracture (normal) groups without significant age differences. Gene expression analysis of RNA obtained from femoral head cartilage revealed that CCN3 and MMP-13 expression in the non-weight-bearing part was significantly higher in the OA group than in the normal group, whereas the weight-bearing OA parts and normal cartilage showed no significant differences in the expression of these genes. The expression of COL10A1, however, was significantly higher in weight-bearing OA parts compared with normal weight-bearing parts, and was also higher in weight-bearing parts compared with non-weight-bearing parts in the OA group. In contrast, OA primary chondrocytes from weight-bearing parts showed higher expression of CCN3, p16, ADAMTS4, and IL-1β than chondrocytes from the corresponding normal group, and higher ADAMTS4 and IL-1β in the non-weight-bearing part compared with the corresponding normal group. Acan expression was significantly lower in the non-weight-bearing group in OA primary chondrocytes than in the corresponding normal chondrocytes. The expression level of CCN3 did not show significant differences between the weight-bearing part and non-weight-bearing part in both OA and normal primary chondrocytes. Immunohistochemical analysis showed accumulated CCN3 and aggrecan neoepitope staining in both the weight-bearing part and non-weight-bearing part in the OA group compared with the normal group. The CCN3 expression level in cartilage had a positive correlation with the Mankin score. X-ray analysis of cartilage-specific CCN3 overexpression mice (Tg) revealed deformation of the femoral and humeral head in the early stage, and immunohistochemical analysis showed accumulated aggrecan neoepitope staining as well as CCN3 staining and the roughening of the joint surface in Tg femoral and humeral heads. Primary chondrocytes from the Tg femoral head showed enhanced expression of Ccn3, Adamts5, p16, Il-6, and Tnfα, and decreased expression of Col2a1 and -an. These findings indicate a correlation between OA degenerative changes and the expression of CCN3, irrespective of age and mechanical loading. Furthermore, the Mankin score indicates that the expression level of Ccn3 correlates with the progression of OA.

    DOI： 10.3390/ijms232315311

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  • Fibroblast Growth Factors and Cellular Communication Network Factors: Intimate Interplay by the Founding Members in Cartilage. Reviewed International journal

    Satoshi Kubota, Eriko Aoyama, Masaharu Takigawa, Takashi Nishida

    International journal of molecular sciences   23 ( 15 )   2022.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    Fibroblast growth factors (FGFs) constitute a large family of signaling molecules that act in an autocrine/paracrine, endocrine, or intracrine manner, whereas the cellular communication network factors (CCN) family is composed of six members that manipulate extracellular signaling networks. FGFs and CCNs are structurally and functionally distinct, except for the common characteristics as matricellular proteins. Both play significant roles in the development of a variety of tissues and organs, including the skeletal system. In vertebrates, most of the skeletal parts are formed and grow through a process designated endochondral ossification, in which chondrocytes play the central role. The growth plate cartilage is the place where endochondral ossification occurs, and articular cartilage is left to support the locomotive function of joints. Several FGFs, including FGF-2, one of the founding members of this family, and all of the CCNs represented by CCN2, which is required for proper skeletal development, can be found therein. Research over a decade has revealed direct binding of CCN2 to FGFs and FGF receptors (FGFRs), which occasionally affect the biological outcome via FGF signaling. Moreover, a recent study uncovered an integrated regulation of FGF and CCN genes by FGF signaling. In this review, after a brief introduction of these two families, molecular and genetic interactions between CCN and FGF family members in cartilage, and their biological effects, are summarized. The molecular interplay represents the mutual involvement of the other in their molecular functions, leading to collaboration between CCN2 and FGFs during skeletal development.

    DOI： 10.3390/ijms23158592

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  • Effect of Angiotensin II on Chondrocyte Degeneration and Protection via Differential Usage of Angiotensin II Receptors Invited Reviewed International journal

    Takashi Nishida, Sho Akashi, Masaharu Takigawa, Satoshi Kubota

    International Journal of Molecular Sciences   22 ( 17 )   9204 - 9204   2021.8

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    The renin–angiotensin system (RAS) controls not only systemic functions, such as blood pressure, but also local tissue-specific events. Previous studies have shown that angiotensin II receptor type 1 (AT1R) and type 2 (AT2R), two RAS components, are expressed in chondrocytes. However, the angiotensin II (ANG II) effects exerted through these receptors on chondrocyte metabolism are not fully understood. In this study, we investigated the effects of ANG II and AT1R blockade on chondrocyte proliferation and differentiation. Firstly, we observed that ANG II significantly suppressed cell proliferation and glycosaminoglycan content in rat chondrocytic RCS cells. Additionally, ANG II decreased CCN2, which is an anabolic factor for chondrocytes, via increased MMP9. In Agtr1a-deficient RCS cells generated by the CRISPR-Cas9 system, Ccn2 and Aggrecan (Acan) expression increased. Losartan, an AT1R antagonist, blocked the ANG II-induced decrease in CCN2 production and Acan expression in RCS cells. These findings suggest that AT1R blockade reduces ANG II-induced chondrocyte degeneration. Interestingly, AT1R-positive cells, which were localized on the surface of the articular cartilage of 7-month-old mice expanded throughout the articular cartilage with aging. These findings suggest that ANG II regulates age-related cartilage degeneration through the ANG II–AT1R axis.

    DOI： 10.3390/ijms22179204

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  • RFX1‐mediated CCN3 induction that may support chondrocyte survival under starved conditions Reviewed

    Tomomi Mizukawa, Takashi Nishida, Sho Akashi, Kazumi Kawata, Sumire Kikuchi, Harumi Kawaki, Masaharu Takigawa, Hiroshi Kamioka, Satoshi Kubota

    Journal of Cellular Physiology   236 ( 10 )   6884 - 6896   2021.3

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    DOI： 10.1002/jcp.30348

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  • Bipartite regulation of cellular communication network factor 2 and fibroblast growth factor 1 genes by fibroblast growth factor 1 through histone deacetylase 1 and fork head box protein A1 Reviewed International journal

    Abdellatif Elseoudi, Takashi Nishida, Tomomi Mizukawa, Takako Hattori, Kazumi Kawata, Eman A. Taha, Masaharu Takigawa, Satoshi Kubota

    Journal of Cell Communication and Signaling   15 ( 1 )   81 - 91   2021.3

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    Fibroblast growth factor 1 (FGF-1) is the first FGF family member, and it induces proliferation of fibroblasts and other types of the cells. However, recent studies are uncovering unexpected functions of this molecule. Our previous study redefined this growth factor as a catabolic molecule produced in cartilage upon metabolic insult. Indeed, FGF-1 was found to repress the gene expression of cellular communication network factor 2 (CCN2), which protects and regenerates cartilage, amplifying its own production through positive feedback regulation. In the present study, we investigated the molecular mechanism of this bipartite CCN2 repression and FGF1 activation by FGF-1 in chondrocytes. Repression of CCN2 and induction of FGF1 in human chondrocytic cells were both partly abolished by valproic acid, an inhibitor of histone deacetylase 1 (HDAC1), indicating the involvement of chromatin remodeling by histone acetylation in this system. In contrast, RNA degradation analysis suggested no contribution of post-transcriptional regulation of the mRNA stability to the effects conferred by FGF-1. Suspecting a regulation by a specific transcription factor, we next sought a candidate in silico from a large dataset. As a result, we found fork head box protein A1 (FOXA1) as the transcription factor that bound to both CCN2 and FGF1 loci. Functional analysis demonstrated that FOXA1 silencing significantly attenuated the CCN2 repression and FGF1 induction caused by FGF1. These findings collectively indicate that the bipartite regulation by FGF-1 is enabled by the combination of chromatin remodeling by HDACs and transcriptional modulation by FOXA1 with unknown transcriptional coactivators of opposite functionalities.

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  • Suppression of adipocyte differentiation by low‐intensity pulsed ultrasound via inhibition of insulin signaling and promotion of CCN family protein 2 Reviewed International journal

    Takashi Nishida, Yurika Nagao, Satoko Hashitani, Nobuyasu Yamanaka, Masaharu Takigawa, Satoshi Kubota

    Journal of Cellular Biochemistry   121 ( 12 )   4724 - 4740   2020.12

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    Adipocyte differentiation is regulated by several transcription factors such as the CCAAT/enhancer-binding proteins (C/EBPs) and peroxisome proliferator-activated receptor-γ (PPARγ). Here, we demonstrate that low-intensity pulsed ultrasound (LIPUS) suppressed differentiation into mature adipocytes via multiple signaling pathways. When C3H10T1/2, a mesenchymal stem cell line, was treated with LIPUS (3.0 MHz, 60 mW/cm2 ) for 20 minutes once a day for 4 days during adipogenesis, and both the number of lipid droplets and the gene expression of PPARγ and C/EBPα were significantly decreased. Furthermore, LIPUS treatment decreased the phosphorylation of the insulin receptor and also that of Akt and ERK1/2, which are located downstream of this receptor. Next, we showed that LIPUS suppressed the gene expression of angiotensinogen (AGT), which is an adipokine produced by mature adipocytes, as well as that of angiotensin-converting enzyme 1 (ACE1) and angiotensin receptor type 1 (AT1 R) during adipogenesis of pre-adipogenic 3T3-L1 cells. Next, the translocation of Yes-associated protein (YAP) into the nucleus of 3T3-L1 cells was promoted by LIPUS, leading to upregulation of CCN family protein 2 (CCN2), a cellular communication network factor. Moreover, forced expression of CCN2 in 3T3-L1 cells decreased PPARγ gene expression, but it did not increase alkaline phosphatase and osterix gene expression. Finally, gene silencing of CCN2 in C3H10T1/2 cells diminished the effect of LIPUS on the gene expression of PPARγ and C/EBPα. These findings suggest that LIPUS suppressed adipogenesis through inhibition of insulin signaling and decreased PPARγ expression via increased CCN2 production, resulting in a possible decrease of mature adipocytes.

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  • CCN3 (NOV) Drives Degradative Changes in Aging Articular Cartilage Reviewed International journal

    Miho Kuwahara, Koichi Kadoya, Sei Kondo, Shanqi Fu, Yoshiko Miyake, Ayako Ogo, Mitsuaki Ono, Takayuki Furumatsu, Eiji Nakata, Takako Sasaki, Shogo Minagi, Masaharu Takigawa, Satoshi Kubota, Takako Hattori

    International Journal of Molecular Sciences   21 ( 20 )   7556 - 7556   2020.10

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    Aging is a major risk factor of osteoarthritis, which is characterized by the degeneration of articular cartilage. CCN3, a member of the CCN family, is expressed in cartilage and has various physiological functions during chondrocyte development, differentiation, and regeneration. Here, we examine the role of CCN3 in cartilage maintenance. During aging, the expression of Ccn3 mRNA in mouse primary chondrocytes from knee cartilage increased and showed a positive correlation with p21 and p53 mRNA. Increased accumulation of CCN3 protein was confirmed. To analyze the effects of CCN3 in vitro, either primary cultured human articular chondrocytes or rat chondrosarcoma cell line (RCS) were used. Artificial senescence induced by H2O2 caused a dose-dependent increase in Ccn3 gene and CCN3 protein expression, along with enhanced expression of p21 and p53 mRNA and proteins, as well as SA-β gal activity. Overexpression of CCN3 also enhanced p21 promoter activity via p53. Accordingly, the addition of recombinant CCN3 protein to the culture increased the expression of p21 and p53 mRNAs. We have produced cartilage-specific CCN3-overexpressing transgenic mice, and found degradative changes in knee joints within two months. Inflammatory gene expression was found even in the rib chondrocytes of three-month-old transgenic mice. Similar results were observed in human knee articular chondrocytes from patients at both mRNA and protein levels. These results indicate that CCN3 is a new senescence marker of chondrocytes, and the overexpression of CCN3 in cartilage may in part promote chondrocyte senescence, leading to the degeneration of articular cartilage through the induction of p53 and p21.

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  • Regulation of cellular communication network factor 2 (CCN2) in breast cancer cells via the cell-type dependent interplay between CCN2 and glycolysis Reviewed International journal

    Sho Akashi, Takashi Nishida, Tomomi Mizukawa, Kazumi Kawata, Masaharu Takigawa, Seiji Iida, Satoshi Kubota

    Journal of Oral Biosciences   62 ( 3 )   280 - 288   2020.9

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    OBJECTIVES: Anti-osteoclastic treatments for breast cancer occasionally cause medication-related osteonecrosis of the jaw. Moreover, elevated glycolytic activity, which is known as the Warburg effect, is usually observed in these breast cancer cells. Previously, we found that cellular communication network factor 2 (CCN2) production and glycolysis enhanced each other in chondrocytes. Here, we evaluated the interplay between CCN2 and glycolysis in breast cancer cells, as we suspected a possible involvement of CCN2 in the Warburg effect in highly invasive breast cancer cells. METHODS: Two human breast cancer cell lines with a distinct phenotype were used. Glycolysis was inhibited by using 2 distinct compounds, and gene silencing was performed using siRNA. Glycolysis and the expression of relevant genes were monitored via colorimetric assays and quantitative RT-PCR, respectively. RESULTS: Although CCN2 expression was almost completely silenced when treating invasive breast cancer cells with a siRNA cocktail against CCN2, glycolytic activity was not affected. Notably, the expression of glycolytic enzyme genes, which was repressed by CCN2 deficiency in chondrocytes, tended to increase upon CCN2 silencing in breast cancer cells. Inhibition of glycolysis, which resulted in the repression of CCN2 expression in chondrocytic cells, did not alter or strongly enhanced CCN2 expression in the invasive and non-invasive breast cancer cells, respectively. CONCLUSIONS: High CCN2 expression levels play a critical role in the invasion and metastasis of breast cancer. Thus, a collapse in the intrinsic repressive machinery of CCN2 due to glycolysis may induce the acquisition of an invasive phenotype in breast cancer cells.

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  • Hypoxic induction of CCN2 mRNA through p38 MAP kinase activation in the human chondrosarcoma‐derived cell line, HCS‐2/8 Reviewed

    Aya Yoshino, Shiho Hashiguchi, Ryosuke Mano, Seiji Kondo, Satoshi Kubota, Masaharu Takigawa

    Oral Science International   2020.7

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    DOI： 10.1002/osi2.1076

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  • CTGF/CCN2 facilitates LRP4-mediated formation of the embryonic neuromuscular junction. Reviewed International journal

    Bisei Ohkawara, Akinori Kobayakawa, Shunsuke Kanbara, Takako Hattori, Satoshi Kubota, Mikako Ito, Akio Masuda, Masaharu Takigawa, Karen M Lyons, Naoki Ishiguro, Kinji Ohno

    EMBO reports   21 ( 8 )   e48462   2020.6

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    At the neuromuscular junction (NMJ), lipoprotein-related receptor 4 (LRP4) mediates agrin-induced MuSK phosphorylation that leads to clustering of acetylcholine receptors (AChRs) in the postsynaptic region of the skeletal muscle. Additionally, the ectodomain of LRP4 is necessary for differentiation of the presynaptic nerve terminal. However, the molecules regulating LRP4 have not been fully elucidated yet. Here, we show that the CT domain of connective tissue growth factor (CTGF/CCN2) directly binds to the third beta-propeller domain of LRP4. CTGF/CCN2 enhances the binding of LRP4 to MuSK and facilitates the localization of LRP4 on the plasma membrane. CTGF/CCN2 enhances agrin-induced MuSK phosphorylation and AChR clustering in cultured myotubes. Ctgf-deficient mouse embryos (Ctgf-/- ) have small AChR clusters and abnormal dispersion of synaptic vesicles along the motor axon. Ultrastructurally, the presynaptic nerve terminals have reduced numbers of active zones and mitochondria. Functionally, Ctgf-/- embryos exhibit impaired NMJ signal transmission. These results indicate that CTGF/CCN2 interacts with LRP4 to facilitate clustering of AChRs at the motor endplate and the maturation of the nerve terminal.

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  • Selective Agonists of Nuclear Retinoic Acid Receptor Gamma Inhibit Growth of HCS‐2/8 Chondrosarcoma Cells Reviewed International journal

    William P. Shield, Ashley Cellini, Hongying Tian, Kim Wilson, Yang Dan, Joshua M. Abzug, Sonia Garcia, Norifumi Moritani, Ivan Alferiev, Michael Chorny, Masaharu Takigawa, Vincent Y. Ng, Masahiro Iwamoto, Motomi Enomoto‐Iwamoto

    Journal of Orthopaedic Research   38 ( 5 )   1045 - 1051   2020.5

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    Chondrosarcoma is the second most common primary bone sarcoma. Treatment of chondrosarcoma is limited to surgery due to radiation and chemotherapy resistance of this cancer. An ideal treatment for chondrosarcoma would be a well-tolerated, minimally invasive local or systemic treatment modality to halt or slow tumor growth prior to resection of local, unresectable local, or metastatic disease. Palovarotene, an agonist of nuclear retinoic acid receptor γ (RARγ) has shown therapeutic action for treatment of heterotopic ossification and osteochondroma without serious adverse effects in animal models. We hypothesized that selective agonists of RARγ would have an inhibitory effect on chondrosarcoma. All human chondrosarcoma specimens expressed RARγ as determined by immunohistochemical staining. The ΗCS-2/8 chondrosarcoma cell line, established from low-grade human chondrosarcoma, was used to examine the actions of RARγ agonists. In ΗCS2/8 pellet cultures, RARγ agonist treatment reduced the mass size and significantly decreased total glycosaminoglycan, protein amounts, and gene expression levels of cartilage matrix molecules when compared with control groups. Systemic treatment with RARγ agonists significantly inhibited the growth of ΗCS-2/8 cell transplants in vivo. Furthermore, local injection of RARγ agonist-loaded poly-lactic acid nanoparticles induced regression of the mass size of the transplants. Histologic analysis demonstrated that RARγ agonist treatment inhibited cell proliferation activity and stimulated encapsulation of the tumor. These findings indicate that RARγ agonists, including palovarotene, may have an anti-tumor effect on low-grade chondrosarcomas. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1045-1051, 2020.

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  • Roles of Interaction between CCN2 and Rab14 in Aggrecan Production by Chondrocytes. Reviewed International journal

    Mitsuhiro Hoshijima, Takako Hattori, Eriko Aoyama, Takashi Nishida, Satoshi Kubota, Hiroshi Kamioka, Masaharu Takigawa

    International journal of molecular sciences   21 ( 8 )   2020.4

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    To identify proteins that cooperate with cellular communication network factor 2 (CCN2), we carried out GAL4-based yeast two-hybrid screening using a cDNA library derived from the chondrocytic cell line HCS-2/8. Rab14 GTPase (Rab14) polypeptide was selected as a CCN2-interactive protein. The interaction between CCN2 and Rab14 in HCS-2/8 cells was confirmed using the in situ proximity ligation assay. We also found that CCN2 interacted with Rab14 through its IGFBP-like domain among the four domains in CCN2 protein. To detect the colocalization between CCN2 and Rab14 in the cells in detail, CCN2, wild-type Rab14 (Rab14WT), a constitutive active form (Rab14CA), and a dominant negative form (Rab14DN) of Rab14 were overexpressed in monkey kidney-tissue derived COS7 cells. Ectopically overexpressed Rab14 showed a diffuse cytosolic distribution in COS7 cells; however, when Rab14WT was overexpressed with CCN2, the Rab14WT distribution changed to dots that were evenly distributed within the cytosol, and both Rab14 and CCN2 showed clear colocalization. When Rab14CA was overexpressed with CCN2, Rab14CA and CCN2 also showed good localization as dots, but their distribution was more widespread within cytosol. The coexpression of Rab14DN and CCN2 also showed a dotted codistribution but was more concentrated in the perinuclear area. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed that the reduction in RAB14 or CCN2 mRNA by their respective siRNA significantly enhanced the expression of ER stress markers, BIP and CHOP mRNA in HCS-2/8 chondrocytic cells, suggesting that ER and Golgi stress were induced by the inhibition of membrane vesicle transfer via the suppression of CCN2 or Rab14. Moreover, to study the effect of the interaction between CCN2 and its interactive protein Rab14 on proteoglycan synthesis, we overexpressed Rab14WT or Rab14CA or Rab14DN in HCS-2/8 cells and found that the overexpression of Rab14DN decreased the extracellular proteoglycan accumulation more than the overexpression of Rab14WT/CA did in the chondrocytic cells. These results suggest that intracellular CCN2 is associated with Rab14 on proteoglycan-containing vesicles during their transport from the Golgi apparatus to endosomes in chondrocytes and that this association may play a role in proteoglycan secretion by chondrocytes.

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  • Extracellular Vesicles Enriched with Moonlighting Metalloproteinase Are Highly Transmissive, Pro-Tumorigenic, and Trans-Activates Cellular Communication Network Factor (CCN2/CTGF): CRISPR against Cancer Reviewed

    Yuka Okusha, Takanori Eguchi, Manh T. Tran, Chiharu Sogawa, Kaya Yoshida, Mami Itagaki, Eman A. Taha, Kisho Ono, Eriko Aoyama, Hirohiko Okamura, Ken-ichi Kozaki, Stuart K. Calderwood, Masaharu Takigawa, Kuniaki Okamoto

    Cancers   12 ( 4 )   881 - 881   2020.4

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    DOI： 10.3390/cancers12040881

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  • Antiparkinson Drug Benztropine Suppresses Tumor Growth, Circulating Tumor Cells, and Metastasis by Acting on SLC6A3/DAT and Reducing STAT3 Reviewed International journal

    Chiharu Sogawa, Takanori Eguchi, Manh Tien Tran, Masayuki Ishige, Kilian Trin, Yuka Okusha, Eman Ahmed Taha, Yanyin Lu, Hotaka Kawai, Norio Sogawa, Masaharu Takigawa, Stuart K. Calderwood, Kuniaki Okamoto, Ken-ichi Kozaki

    Cancers   12 ( 2 )   523 - 523   2020.2

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    Tumor growth, progression, and therapy resistance are crucial factors in the prognosis of cancer. The properties of three-dimensional (3D) tumor-like organoids (tumoroids) more closely resemble in vivo tumors compared to two-dimensionally cultured cells and are therefore effectively used for assays and drug screening. We here established a repurposed drug for novel anticancer research and therapeutics using a 3D tumoroid-based screening system. We screened six pharmacologically active compounds by using an original tumoroid-based multiplex phenotypic screening system with a matrix metalloproteinase 9 (MMP9) promoter-driven fluorescence reporter for the evaluation of both tumoroid formation and progression. The antiparkinson drug benztropine was the most effective compound uncovered by the screen. Benztropine significantly inhibited in vitro tumoroid formation, cancer cell survival, and MMP9 promoter activity. Benztropine also reduced the activity of oncogenic signaling transducers and trans-activators for MMP9, including STAT3, NF-κB, and β-catenin, and the properties of cancer stem cells/cancer-initiating cells. Benztropine and GBR-12935 directly targeted the dopamine transporter DAT/SLC6A3, whose genetic alterations such as amplification were correlated with poor prognosis for cancer patients. Benztropine also inhibited the tumor growth, circulating tumor cell (CTC) number, and rate of metastasis in a tumor allograft model in mice. In conclusion, we propose the repurposing of benztropine for anticancer research and therapeutics that can suppress tumor progression, CTC, and metastasis of aggressive cancers by reducing key pro-tumorigenic factors.

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  • Extracellular Oncosomes Rich in Moonlighting Metalloproteinase (MMP3) Are Transmissive, Pro-Tumorigenic, and Induces Cellular Communication Network Factor 2 (CCN2/CTGF): CRISPR against Cancer

    Yuka Okusha, Takanori Eguchi, Manh Tien Tran, Chiharu Sogawa, Kaya Yoshida, Mami Itagaki, Eman Ahmed Taha, Kisho Ono, Eriko Aoyama, Hirohiko Okamura, Ken-ichi Kozaki, Stuart K. Calderwood, Masaharu Takigawa, Kuniaki Okamoto

    Preprints   doi: 10.20944/preprints202002.0281.v1   2020.2

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    Matrix metalloproteinase 3 (MMP3) plays multiple roles in pro-tumorigenic proteolysis and in intracellular transcription. These include inducing connective tissue growth factor [CTGF, also known as cellular communication network factor 2 (CCN2)] and prompting a new definition of MMP3 as a moonlighting metalloproteinase. Members of the MMP family have been found within tumor-derived extracellular vesicles (EVs) such as oncosomes or exosomes. We here investigated the roles of MMP3-rich oncosomes in tumor progression, molecular transmission, and gene regulation. MMP3 and CCN2/CTGF were significantly co-expressed in tumor samples derived from patients suffering from colorectal adenocarcinoma. We found that oncosomes derived from a rapidly metastatic colon cancer cells (LuM1) were enriched in MMP3 and a C-terminal half fragment of CCN2/CTGF. MMP3-rich oncosomes were highly transmissive into recipient cells and were pro-tumorigenic in an allograft mouse model. Oncosome-derived MMP3 was transmissive into recipient cell nuclei, trans-activated CCN2/CTGF promoter, and induced CCN2/CTGF production at 1 to 6 hours after the addition of oncosomes to culture media. In addition, CRISPR/Cas9-mediated knockout of MMP3 showed significant anti-tumor effects, including inhibition of migration and invasion of LuM1 cells in vitro, inhibition of tumor growth in vivo, and reduction of CCN2/CTGF and its promoter activity in vitro. These data newly demonstrate that the oncosome-derived moonlighting metalloproteinase promotes metastasis and is pro-tumorigenic at distant sites as well as a transmissive trans-activator for the cellular communication network gene.

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  • Triple knockdown of CDC37, HSP90-alpha and HSP90-beta diminishes extracellular vesicles-driven malignancy events and macrophage M2 polarization in oral cancer Reviewed International journal

    Kisho Ono, Chiharu Sogawa, Hotaka Kawai, Manh Tien Tran, Eman A. Taha, Yanyin Lu, May Wathone Oo, Yuka Okusha, Hirohiko Okamura, Soichiro Ibaragi, Masaharu Takigawa, Ken-Ichi Kozaki, Hitoshi Nagatsuka, Akira Sasaki, Kuniaki Okamoto, Stuart K. Calderwood, Takanori Eguchi

    Journal of Extracellular Vesicles   9 ( 1 )   1769373 - 1769373   2020.1

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    Evidence has been accumulating to indicate that extracellular vesicles (EVs), including exosomes, released by cancer cells can foster tumour progression. The molecular chaperones - CDC37, HSP90α and HSP90β play key roles in cancer progression including epithelial-mesenchymal transition (EMT), although their contribution to EVs-mediated cell-cell communication in tumour microenvironment has not been thoroughly examined. Here we show that triple depletion of the chaperone trio attenuates numerous cancer malignancy events exerted through EV release. Metastatic oral cancer-derived EVs (MEV) were enriched with HSP90α HSP90β and cancer-initiating cell marker CD326/EpCAM. Depletion of these chaperones individually induced compensatory increases in the other chaperones, whereas triple siRNA targeting of these molecules markedly diminished the levels of the chaperone trio and attenuated EMT. MEV were potent agents in initiating EMT in normal epithelial cells, a process that was attenuated by the triple chaperone depletion. The migration, invasion, and in vitro tumour initiation of oral cancer cells were significantly promoted by MEV, while triple depletion of CDC37/HSP90α/β reversed these MEV-driven malignancy events. In metastatic oral cancer patient-derived tumours, HSP90β was significantly accumulated in infiltrating tumour-associated macrophages (TAM) as compared to lower grade oral cancer cases. HSP90-enriched MEV-induced TAM polarization to an M2 phenotype, a transition known to support cancer progression, whereas the triple chaperone depletion attenuated this effect. Mechanistically, the triple chaperone depletion in metastatic oral cancer cells effectively reduced MEV transmission into macrophages. Hence, siRNA-mediated knockdown of the chaperone trio (CDC37/HSP90α/HSP90β) could potentially be a novel therapeutic strategy to attenuate several EV-driven malignancy events in the tumour microenvironment. Abbreviations: CDC37: cell division control 37; EMT: epithelial-mesenchymal transmission; EV: extracellular vesicles; HNSCC: head and neck squamous cell carcinoma; HSP90: heat shock protein 90; TAM: tumour-associated macrophage.

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  • Jiadifenolide induces expression of cellular communication network factor (CCN) genes, and CCN2 possesses neurotrophic activity in neuronal precursor cells derived from human induced pluripotent stem cells. Reviewed International journal

    Shoji M, Ueda M, Nishioka M, Hiroki Minato, M, Kenichi Harada, Kubo M, Fukuyama Y, Suzuki Y, Aoyama E, Takigawa M, Kuzuhara T

    Biochem Biophys Res Commun   519 ( 2 )   309 - 315   2019.11

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    Jiadifenolide has been reported to have neurotrophin-like activity in primary rat cortical neurons, and also possesses neurotrophic effects in neuronal precursor cells derived from human induced pluripotent stem cells (hiPSCs), as we have previously reported. However, the molecular mechanisms by which jiadifenolide exerts its neurotrophic effects in rat and human neurons are unknown. Thus, we aimed to investigate the molecular mechanisms and pathways by which jiadifenolide promotes neurotrophic effects. Here, we found that jiadifenolide activated cellular communication network factor (CCN) signaling pathways by up-regulating mRNA level expression of CCN genes in human neuronal cells. We also found that CCN2 (also known as connective tissue growth factor, CTGF) protein promotes neurotrophic effects through activation of the p44/42 mitogen-activated protein kinase signaling pathway. This is the first discovery which links neurotrophic activity with CCN signaling.

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  • Roles of matricellular CCN2 deposited by osteocytes in osteoclastogenesis and osteoblast differentiation. Reviewed

    Nishida T, Kubota S, Yokoi H, Mukoyama, M, Takigawa M

    Sci Rep   9 ( 1 )   10913   2019.7

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  • Possible reparative effect of low-intensity pulsed ultrasound (LIPUS) on injured meniscus. Reviewed International journal

    Kamatsuki K, Aoyama E, Furumatsu T, Miyazawa S, Maehara A, Yamanaka N, Nishida T, Kubota S, Ozaki T, Takigawa M

    J Cell Commun Signal   13 ( 2 )   193 - 207   2019.6

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    Menisci are a pair of crescent-shaped fibrocartilages, particularly of which their inner region of meniscus is an avascular tissue. It has characteristics similar to those of articular cartilage, and hence is inferior in healing. We previously reported that low-intensity pulsed ultrasound (LIPUS) treatment stimulates the production of CCN2/CTGF, a protein involved in repairing articular cartilage, and the gene expression of major cartilage matrices such as type II collagen and aggrecan in cultured chondrocytes. Therefore, in this present study, we investigated whether LIPUS has also favorable effect on meniscus cells and tissues. LIPUS applied with a 60 mW/cm2 intensity for 20 min stimulated the gene expression and protein production of CCN2 via ERK and p38 signaling pathways, as well as gene expression of SOX9, aggrecan, and collagen type II in human inner meniscus cells in culture, and slightly stimulated the gene expression of CCN2 and promoted the migration in human outer meniscus cells in culture. LIPUS also induced the expression of Ccn2, Sox9, Col2a1, and Vegf in rat intact meniscus. Furthermore, histological evaluations showed that LIPUS treatment for 1 to 4 weeks promoted healing of rat injured lateral meniscus, as evidenced by better and earlier angiogenesis and extracellular matrix synthesis. The data presented indicate that LIPUS treatment might prevent meniscus from degenerative change and exert a reparative effect on injured meniscus via up-regulation of repairing factors such as CCN2 and that it might thus be useful for treatment of an injured meniscus as a non-invasive therapy.

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  • The BMP-2 mutant L51P: a BMP receptor IA binding-deficient inhibitor of noggin Reviewed

    Hany Mohamed Khattab, Satoshi Kubota, Masaharu Takigawa, Takuo Kuboki, Walter Sebald

    JOURNAL OF BONE AND MINERAL METABOLISM   37 ( 2 )   199 - 205   2019.3

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  • CCN2/CTGF binds the small leucine rich proteoglycan protein Tsukushi Reviewed

    Ohta K, Aoyama E, Ahmad SAI, Ito N, Anam MB, Kubota S, Takigawa M

    J Cell Commun Signal.   13 ( 1 )   113 - 118   2019.3

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  • A reporter system evaluates tumorigenesis, metastasis, β-catenin/MMP regulation, and druggability. Reviewed

    Sogawa C, Eguchi T, Okusha Y, Ono K, Ohyama K, Iizuka M, Kawasaki R, Hamada Y, Takigawa M, Sogawa N, Okamoto K, Kozaki KI

    Tissue Eng Part A   13 ( 2 )   193 - 207   2019.2

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  • Physiological role of urothelial cancer-associated one long noncoding RNA in human skeletogenic cell differentiation. Reviewed

    Ishikawa T, Nishida T, Ono M, Takarada T, Nguyen HT, Kurihara S, Furumatsu T, Murase Y, Takigawa M, Oohashi T, Kamioka H, Kubota S

    J Cell Physiol   233 ( 6 )   4825 - 4840   2018.7

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  • Depletion of Lipid Efflux Pump ABCG1 Triggers the Intracellular Accumulation of Extracellular Vesicles and Reduces Aggregation and Tumorigenesis of Metastatic Cancer Cells. Reviewed International journal

    Yuri Namba, Chiharu Sogawa, Yuka Okusha, Hotaka Kawai, Mami Itagaki, Kisho Ono, Jun Murakami, Eriko Aoyama, Kazumi Ohyama, Jun-Ichi Asaumi, Masaharu Takigawa, Kuniaki Okamoto, Stuart K Calderwood, Ken-Ichi Kozaki, Takanori Eguchi

    Frontiers in oncology   119 ( 6 )   4352 - 4360   2018.6

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    The ATP-binding cassette transporter G1 (ABCG1) is a cholesterol lipid efflux pump whose role in tumor growth has been largely unknown. Our transcriptomics revealed that ABCG1 was powerfully expressed in rapidly metastatic, aggregative colon cancer cells, in all the ABC transporter family members. Coincidently, genetic amplification of ABCG1 is found in 10-35% of clinical samples of metastatic cancer cases. Expression of ABCG1 was further elevated in three-dimensional tumoroids (tumor organoids) within stemness-enhancing tumor milieu, whereas depletion of ABCG1 lowered cellular aggregation and tumoroid growth in vitro as well as hypoxia-inducible factor 1α in cancer cells around the central necrotic areas in tumors in vivo. Notably, depletion of ABCG1 triggered the intracellular accumulation of extracellular vesicles (EVs) and regression of tumoroids. Collectively, these data suggest that ABCG1 plays a crucial role in tumorigenesis in metastatic cancer and that depletion of ABCG1 triggers tumor regression with the accumulation of EVs and their derivatives and cargos, implicating a novel ABCG1-targeting therapeutic strategy by which redundant and toxic substances may be accumulated in tumors leading to their regression.

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  • Low-intensity pulsed ultrasound stimulation promotes osteoblast differentiation through hedgehog signaling. Reviewed International journal

    Kenichi Matsumoto, Tsuyoshi Shimo, Naito Kurio, Tatsuo Okui, Soichiro Ibaragi, Yuki Kunisada, Kyoichi Obata, Masanori Masui, Pang Pai, Yuu Horikiri, Nobuyuki Yamanaka, Masaharu Takigawa, Akira Sasaki

    Journal of cellular biochemistry   119 ( 6 )   4352 - 4360   2018.6

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    Low-intensity pulsed ultrasound (LIPUS) has been used as an adjunct to fracture healing therapies, but the mechanisms underlying its action are not known. We reported that sonic hedgehog (SHH) signaling was activated in osteoblasts at the dynamic remodeling site of a bone fracture. Mechanical stimulation is a crucial factor in bone remodeling, and it is related to the primary cilia as a sensor of hedgehog signaling. Here we observed that LIPUS promoted callus formation in accord with Gli2-positive cells after 14 days at the mouse femur fractured site compared with a control group. An immunofluorescence analysis showed that the numbers of primary cilia and cilia/osterix double-positive osteoblasts were increased at the fracture site by LIPUS. LIPUS stimulated not only the number and the length of primary cilia, but also the levels of ciliated protein, Ift88 mRNA, and SHH, Gli1, and Gli2 in MC3T3-E1 cells. Further experiments revealed that LIPUS stimulated osteogenic differentiation in the presence of smoothened agonist (SAG) treatment. These results indicate that LIPUS stimulates osteogenic differentiation and the maturation of osteoblasts by a primary cilium-mediated activation of hedgehog signaling.

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  • The BMP-2 mutant L51P: a BMP receptor IA binding-deficient inhibitor of noggin Reviewed

    Hany Mohamed Khattab, Satoshi Kubota, Masaharu Takigawa, Takuo Kuboki, Walter Sebald

    Journal of Bone and Mineral Metabolism   128 ( 3 )   1 - 7   2018.4

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    DOI： 10.1007/s00774-018-0925-0

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  • An early history of CCN2/CTGF research: the road to CCN2 via hcs24, ctgf, ecogenin, and regenerin Reviewed

    Masaharu Takigawa

    Journal of Cell Communication and Signaling   12 ( 1 )   253 - 264   2018.3

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    DOI： 10.1007/s12079-017-0414-6

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  • Metabolic regulation of the CCN family genes by glycolysis in chondrocytes Reviewed

    Sho Akashi, Takashi Nishida, Abdellatif El-Seoudi, Masaharu Takigawa, Seiji Iida, Satoshi Kubota

    Journal of Cell Communication and Signaling   12 ( 1 )   245 - 252   2018.3

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    DOI： 10.1007/s12079-017-0420-8

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  • Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment Reviewed

    Takanori Eguchi, Chiharu Sogawa, Yuka Okusha, Kenta Uchibe, Ryosuke Iinuma, Kisho Ono, Keisuke Nakano, Jun Murakami, Manabu Itoh, Kazuya Arai, Toshifumi Fujiwara, Yuri Namba, Yoshiki Murata, Kazumi Ohyama, Manami Shimomura, Hirohiko Okamura, Masaharu Takigawa, Tetsuya Nakatsura, Ken-ichi Kozaki, Kuniaki Okamoto, Stuart K. Calderwood

    PLoS ONE   13 ( 2 )   e0191109   2018.2

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    DOI： 10.1371/journal.pone.0191109

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  • A Tumor Suppressor Gene Product, Platelet-Derived Growth Factor Receptor-Like Protein Controls Chondrocyte Proliferation and Differentiation Reviewed

    Kazumi Kawata, Satoshi Kubota, Takanori Eguchi, Eriko Aoyama, Norifumi H. Moritani, Morihiko Oka, Harumi Kawaki, Masaharu Takigawa

    JOURNAL OF CELLULAR BIOCHEMISTRY   118 ( 11 )   4033 - 4044   2017.11

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  • Regulatory mechanism of CCN2 production by serotonin (5-HT) via 5-HT2A and 5-HT2B receptors in chondrocytes Reviewed

    Ayaka Hori, Takashi Nishida, Shogo Takashiba, Satoshi Kubota, Masaharu Takigawa

    PLOS ONE   12 ( 11 )   8630 - 8641   2017.11

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  • Novel role of CCN3 that maintains the differentiated phenotype of articular cartilage Reviewed

    Danilo Janune, Tarek Abd El Kader, Eriko Aoyama, Takashi Nishida, Yasuhiko Tabata, Satoshi Kubota, Masaharu Takigawa

    JOURNAL OF BONE AND MINERAL METABOLISM   35 ( 6 )   582 - 597   2017.11

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    DOI： 10.1007/s00774-016-0793-4

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  • Catabolic effects of FGF-1 on chondrocytes and its possible role in osteoarthritis Reviewed

    Abdellatif El-Seoudi, Tarek Abd El Kader, Takashi Nishida, Takanori Eguchi, Eriko Aoyama, Masaharu Takigawa, Satoshi Kubota

    JOURNAL OF CELL COMMUNICATION AND SIGNALING   11 ( 3 )   255 - 263   2017.9

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  • CATABOLIC EFFECTS OF FGF-1 ON CHONDROCYTES WITH REDUCED CCN2 PRODUCTION THAT PROMOTES CARTILAGE REGENERATION: POSSIBLE ROLE IN OSTEOARTHRITIS

    A. Elseoudi, T. Abd El Kader, T. Nishida, E. Aoyama, T. Eguchi, M. Takigawa, S. Kubota

    OSTEOPOROSIS INTERNATIONAL   28   S225 - S225   2017.7

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  • UPR transducer BBF2H7 allows export of type II collagen in a cargo- and developmental stage-specific manner Reviewed

    Tokiro Ishikawa, Takuya Toyama, Yuki Nakamura, Kentaro Tamada, Hitomi Shimizu, Satoshi Ninagawa, Tetsuya Okada, Yasuhiro Kamei, Tomoko Ishikawa-Fujiwara, Takeshi Todo, Eriko Aoyama, Masaharu Takigawa, Akihiro Harada, Kazutoshi Mori

    JOURNAL OF CELL BIOLOGY   216 ( 6 )   1761 - 1774   2017.6

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  • Low-intensity pulsed ultrasound (LIPUS) treatment of cultured chondrocytes stimulates production of CCN family protein 2 (CCN2), a protein involved in the regeneration of articular cartilage: mechanism underlying this stimulation Reviewed

    T. Nishida, S. Kubota, E. Aoyama, N. Yamanaka, K. M. Lyons, M. Takigawa

    OSTEOARTHRITIS AND CARTILAGE   25 ( 5 )   759 - 769   2017.5

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  • Erratum: Proinsulin C-peptide regulates ribosomal RNA expression (The Journal of Biological Chemistry (2010) 285 (3462-3469) DOI: 10.1074/jbc.M109.053587) Reviewed

    Emma Lindahl, Ulrika Nyman, Farasat Zaman, Carina Palmberg, Anna Cascante, Jawed Shafqat, Masaharu Takigawa, Lars Sävendahl, Hans Jörnvall, Bertrand Joseph

    Journal of Biological Chemistry   285 ( 5 )   3462 - 3469   2017.3

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    DOI： 10.1074/jbc.M109.053587

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  • Proinsulin C-peptide regulates ribosomal RNA expression (vol 292, pg 3467, 2017)

    Emma Lindahl, Ulrika Nyman, Farasat Zaman, Carina Palmberg, Anna Cascante, Jawed Shafqat, Masaharu Takigawa, Lars Saevendahl, Hans Joernvall, Bertrand Joseph

    JOURNAL OF BIOLOGICAL CHEMISTRY   292 ( 10 )   4382 - 4382   2017.3

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  • Intracellular MMP3 Promotes HSP Gene Expression in Collaboration With Chromobox Proteins Reviewed

    Takanori Eguchi, Stuart K. Calderwood, Masaharu Takigawa, Satoshi Kubota, Ken-ichi Kozaki

    JOURNAL OF CELLULAR BIOCHEMISTRY   118 ( 1 )   43 - 51   2017.1

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    DOI： 10.1002/jcb.25607

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  • Immunohistochemical analysis of CCN proteins in calcified tissues

    Harumi Kawaki, Satoshi Kubota, Masaharu Takigawa

    Methods in Molecular Biology   1489   53 - 62   2017

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    DOI： 10.1007/978-1-4939-6430-7_6

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  • Gene expression analysis of CCN proteins: Whole-mount in situ hybridization of Ccn2 in developing calcified tissues

    Tomoichiro Yamaai, Masaharu Takigawa

    Methods in Molecular Biology   1489   11 - 19   2017

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    DOI： 10.1007/978-1-4939-6430-7_2

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  • Western blotting analysis of CCN proteins in calcified tissues

    Harumi Kawaki, Satoshi Kubota, Masaharu Takigawa

    Methods in Molecular Biology   1489   43 - 51   2017

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    DOI： 10.1007/978-1-4939-6430-7_5

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  • The ccn proteins: An overview Invited

    Masaharu Takigawa

    Methods in Molecular Biology   1489   1 - 8   2017

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    DOI： 10.1007/978-1-4939-6430-7_1

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  • In vitro transfection with and expression of CCN family of genes

    Danilo Janune, Masaharu Takigawa

    Methods in Molecular Biology   1489   107 - 113   2017

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    DOI： 10.1007/978-1-4939-6430-7_11

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  • Production of recombinant CCN2 protein by mammalian cells

    Takashi Nishida, Satoshi Kubota, Masaharu Takigawa

    Methods in Molecular Biology   1489   95 - 105   2017

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    DOI： 10.1007/978-1-4939-6430-7_10

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  • Production of recombinant CCN2 protein in Escherichia coli

    Eriko Aoyama, Takako Hattori, Satoshi Kubota, Masaharu Takigawa

    Methods in Molecular Biology   1489   77 - 84   2017

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    DOI： 10.1007/978-1-4939-6430-7_8

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  • Analysis of expression of CCN family genes in skeletal tissue-derived cells

    Harumi Kawaki, Satoshi Kubota, Masaharu Takigawa

    Methods in Molecular Biology   1489   33 - 41   2017

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    DOI： 10.1007/978-1-4939-6430-7_4

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  • In vivo evaluation of cartilage regenerative effects of CCN2 protein

    Takashi Nishida, Satoshi Kubota, Masaharu Takigawa

    Methods in Molecular Biology   1489   273 - 282   2017

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    DOI： 10.1007/978-1-4939-6430-7_25

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  • Cell biological assays for measuring chondrogenic activities of CCN2 protein

    Takashi Nishida, Satoshi Kubota, Masaharu Takigawa

    Methods in Molecular Biology   1489   219 - 237   2017

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    DOI： 10.1007/978-1-4939-6430-7_21

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  • Protein imaging of CCN2 AND CCN3 in living cells

    Takako Hattori, Mitsuhiro Hoshijima, Masaharu Takigawa

    Methods in Molecular Biology   1489   211 - 215   2017

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    DOI： 10.1007/978-1-4939-6430-7_20

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  • Analysis of posttranscriptional regulation of CCN genes

    Seiji Kondo, Satoshi Kubota, Masaharu Takigawa

    Methods in Molecular Biology   1489   187 - 209   2017

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    DOI： 10.1007/978-1-4939-6430-7_19

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  • Evaluation of molecular interaction between CCN2 protein and its binding partners by surface plasmon resonance (SPR)

    Eriko Aoyama, Masaharu Takigawa

    Methods in Molecular Biology   1489   169 - 176   2017

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    DOI： 10.1007/978-1-4939-6430-7_17

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  • Promoter analyses of CCN genes

    Takanori Eguchi, Satoshi Kubota, Masaharu Takigawa

    Methods in Molecular Biology   1489   177 - 185   2017

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    DOI： 10.1007/978-1-4939-6430-7_18

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  • Analysis of signaling pathways activated by CCN proteins

    Harumi Kawaki, Satoshi Kubota, Masaharu Takigawa

    Methods in Molecular Biology   1489   139 - 143   2017

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    DOI： 10.1007/978-1-4939-6430-7_14

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  • Protocols for screening peptide motifs binding to ccn family proteins

    Satoshi Kubota, Harumi Kawaki, Masaharu Takigawa

    Methods in Molecular Biology   1489   155 - 167   2017

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    DOI： 10.1007/978-1-4939-6430-7_16

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  • Elisa of CCN family proteins in body fluids including serum and plasma

    Satoshi Kubota, Harumi Kawaki, Masaharu Takigawa

    Methods in Molecular Biology   1489   127 - 138   2017

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    DOI： 10.1007/978-1-4939-6430-7_13

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  • Protocols for screening for binding partners of CCN proteins: Yeast two-hybrid system

    Mitsuhiro Hoshijima, Takako Hattori, Masaharu Takigawa

    Methods in Molecular Biology   1489   145 - 154   2017

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    DOI： 10.1007/978-1-4939-6430-7_15

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  • Preparation of module-specific antibodies against CCN family members

    Satoshi Kubota, Masaharu Takigawa

    Methods in Molecular Biology   1489   115 - 128   2017

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    DOI： 10.1007/978-1-4939-6430-7_12

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  • 骨リモデリングにおける骨細胞の役割 Invited

    西田崇, 久保田聡, 滝川正春

    Clinical Calcium   27 ( 12 )   23 - 29   2017

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  • Analysis of pathological activities of CCN proteins in bone metastasis Invited

    Tsuyoshi Shimo, Norie Yoshioka, Masaharu Takigawa, Akira Sasaki

    Methods in Molecular Biology   1489   505 - 512   2017

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    DOI： 10.1007/978-1-4939-6430-7_42

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  • Generation and analysis of cartilage-specific CCN2 overexpression in transgenic mice

    Takako Hattori, Shinsuke Itoh, Masaharu Takigawa

    Methods in Molecular Biology   1489   391 - 403   2017

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    DOI： 10.1007/978-1-4939-6430-7_32

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  • Analysis of transcytosis of CCN2 by chondrocytes

    Kazumi Kawata, Satoshi Kubota, Masaharu Takigawa

    Methods in Molecular Biology   1489   405 - 413   2017

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    DOI： 10.1007/978-1-4939-6430-7_33

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  • Cell biological assays for measuring angiogenic activities of CCN proteins

    Tsuyoshi Shimo, Masaharu Takigawa

    Methods in Molecular Biology   1489   239 - 249   2017

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    DOI： 10.1007/978-1-4939-6430-7_22

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  • The role of osteocytes in bone remodeling.

    Nishida, T, Kubota, S, Takigawa, M

    27   23 - 29   2017

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  • Assessment of CCN2 Independent Modules Regenerative Capacity on Osteoarthritis and Further Selecting the Most Suitable Among them as a Potential Therapeutic Drug Reviewed

    Abdelkader Tarek, Aoyama Eriko, Nishida Takashi, Hattori Takako, Janune Danilo, Hara Emilio S, Ono Mitsuaki, Tabata Yasuhiko, Kuboki Takuo, Kubota Satoshi, Takigawa Masaharu

    FASEB JOURNAL   30   2016.4

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  • Assessment of CCN2 Independent Modules Regenerative Capacity on Osteoarthritis and Further Selecting the Most Suitable Among them as a Potential Therapeutic Drug Reviewed

    Abdelkader Tarek, Aoyama Eriko, Nishida Takashi, Hattori Takako, Janune Danilo, Hara Emilio S, Ono Mitsuaki, Tabata Yasuhiko, Kuboki Takuo, Kubota Satoshi, Takigawa Masaharu

    FASEB JOURNAL   30   2016.4

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  • Role of CCN2 in Amino Acid Metabolism of Chondrocytes Reviewed

    Yurika Murase, Takako Hattori, Eriko Aoyama, Takashi Nishida, Aya Maeda-Uematsu, Harumi Kawaki, Karen M. Lyons, Akira Sasaki, Masaharu Takigawa, Satoshi Kubota

    JOURNAL OF CELLULAR BIOCHEMISTRY   117 ( 4 )   927 - 937   2016.4

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  • Matrix remodeling response of human periodontal tissue cells toward fibrosis upon nicotine exposure Reviewed

    Hiroko Takeuchi-Igarashi, Satoshi Kubota, Toshiaki Tachibana, Etsuko Murakashi, Masaharu Takigawa, Masataka Okabe, Yukihiro Numabe

    ODONTOLOGY   104 ( 1 )   35 - 43   2016.1

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    DOI： 10.1007/s10266-014-0177-y

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  • Sorcin Expression in the Epiphyseal Growth Plates of Mice Reviewed

    Mariko Kawai, Ning Liu, Takako Hattori, Yo-Hei Kataoka, Masaharu Takigawa, Satoshi Kubota, Toshio Yamamoto, Kiyoshi Ohura

    JOURNAL OF HARD TISSUE BIOLOGY   25 ( 1 )   57 - 61   2016.1

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  • CCN4/WISP-1 positively regulates chondrogenesis by controlling TGF-beta 3 function Reviewed

    Yoshioka, Yuya, Ono, Mitsuaki, Maeda, Azusa, Kilts, Tina M., Hara, Emilio Satoshi, Khattab, Hany, Ueda, Junji, Aoyama, Eriko, Oohashi, Toshitaka, Takigawa, Masaharu, Young, Marian F., Kuboki, Takuo

    Bone   83   162 - 170   2016

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  • Involvement of multiple CCN family members in platelets that support regeneration of joint tissues Reviewed

    Chikako Hara, Satoshi Kubota, Takashi Nishida, Miki Hiasa, Takako Hattori, Eriko Aoyama, Yoshinori Moriyama, Hiroshi Kamioka, Masaharu Takigawa

    MODERN RHEUMATOLOGY   26 ( 6 )   940 - 949   2016

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  • Physical interaction of CCN2 with diverse growth factors involved in chondrocyte differentiation during endochondral ossification Reviewed

    Hany Mohamed Khattab, Eriko Aoyama, Satoshi Kubota, Masaharu Takigawa

    JOURNAL OF CELL COMMUNICATION AND SIGNALING   9 ( 3 )   247 - 254   2015.9

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  • Identification of transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) as a novel factor for TNF-α expression upon lipopolysaccharide stimulation in human monocytes. Reviewed International journal

    Murata H, Hattori T, Maeda H, Takashiba S, Takigawa M, Kido J, Nagata T

    Journal of periodontal research   50 ( 4 )   452 - 460   2015.8

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    BACKGROUND AND OBJECTIVE: Tumor necrosis factor alpha (TNF-α) is a major cytokine implicated in various inflammatory diseases. The nature of the nuclear factors associated with human TNF-α gene regulation is not well elucidated. We previously identified a novel region located from -550 to -487 in human TNF-α promoter that did not contain the reported binding sites for nuclear factor kappa B (NF-κB) but showed lipopolysaccharide (LPS)-induced transcriptional activity. The purpose of this study is to identify novel factors that bind to the promoter region and regulate TNF-α expression. MATERIAL AND METHODS: To identify DNA-binding proteins that bound to the target region of TNF-α promoter, a cDNA library from LPS-stimulated human monocytic cell line THP-1 was screened using a yeast one-hybrid system. Cellular localizations of the DNA-binding protein in the cells were examined by subcellular immunocytochemistry. Nuclear amounts of the protein in LPS-stimulated THP-1 cells were identified by western blot analysis. Expression of mRNA of the protein in the cells was quantified by real-time polymerase chain reaction. Electrophoretic mobility shift assays were performed to confirm the DNA-binding profile. Overexpression of the protein and knockdown of the gene were also performed to investigate the role for TNF-α expression. RESULTS: Several candidates were identified from the cDNA library and transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) was focused on. Western blot analysis revealed that nuclear TDP-43 protein was increased in the LPS-stimulated THP-1 cells. Expression of TDP-43 mRNA was already enhanced before TNF-α induction by LPS. Electrophoretic mobility shift assay analysis showed that nuclear extracts obtained by overexpressing FLAG-tagged TDP-43 bound to the -550 to -487 TNF-α promoter fragments. Overexpression of TDP-43 in THP-1 cells resulted in an increase of TNF-α expression. Knockdown of TDP-43 in THP-1 cells downregulated TNF-α expression. CONCLUSION: We identified TDP-43 as one of the novel TNF-α factors and found that it bound to the LPS-responsive element in the TNF-α promoter to increase TNF-α expression.

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  • CCN2 enhances RANKL-induced osteoclast differentiation via direct binding to RANK and OPG Reviewed

    Eriko Aoyama, Satoshi Kubota, Hany Mohamed Khattab, Takashi Nishida, Masaharu Takigawa

    BONE   73   242 - 248   2015.4

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    DOI： 10.1016/j.bone.2014.12.058

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  • CCN family protein 2 (CCN2) promotes the early differentiation, but inhibits the terminal differentiation of skeletal myoblasts Reviewed

    Takashi Nishida, Satoshi Kubota, Eriko Aoyama, Danilo Janune, Karen M. Lyons, Masaharu Takigawa

    JOURNAL OF BIOCHEMISTRY   157 ( 2 )   91 - 100   2015.2

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  • Cellular and molecular actions of CCN2/CTGF and its role under physiological and pathological conditions

    Satoshi Kubota, Masaharu Takigawa

    CLINICAL SCIENCE   128 ( 3 )   181 - 196   2015.2

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  • New functional aspects of CCN2 revealed by trans-omic approaches Reviewed

    Kubota, S, Maeda-Uematsu, A, Nishida, T, Takigawa, M

    Journal of Oral Biosciences   57   37 - 43   2015

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  • Role of CCN2 in Amino Acid Metabolism of Chondrocytes.

    Murase Y, Hattori T, Aoyama E, Nishida T, Maeda-Uematsu A, Kawaki H, Lyons KM, Sasaki A, Takigawa M, Kubota S

    J Cell Biochem   151 - 155   2015

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  • Fluocinolone Acetonide Is a Potent Synergistic Factor of TGF-beta 3-Associated Chondrogenesis of Bone Marrow-Derived Mesenchymal Stem Cells for Articular Surface Regeneration Reviewed

    Hara, Emilio Satoshi, Ono, Mitsuaki, Hai Thanh Pham, Sonoyama, Wataru, Kubota, Satoshi, Takigawa, Masaharu, Matsumoto, Takuya, Young, Marian F., Olsen, Bjorn R., Kuboki, Takuo

    Journal of Bone and Mineral Research   30 ( 9 )   1585 - 1596   2015

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  • Exosomes mediate intercellular transfer of pro-fibrogenic connective tissue growth factor (CCN2) between hepatic stellate cells, the principal fibrotic cells in the liver Reviewed

    Alyssa Charrier, Ruju Chen, Li Chen, Sherri Kemper, Takako Hattori, Masaharu Takigawa, David R. Brigstock

    SURGERY   156 ( 3 )   548 - 555   2014.9

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  • Direct interaction between CCN family protein 2 and fibroblast growth factor 1

    Tarek Abd El Kader, Satoshi Kubota, Ken Anno, Saho Tanaka, Takashi Nishida, Takayuki Furumatsu, Eriko Aoyama, Takuo Kuboki, Masaharu Takigawa

    JOURNAL OF CELL COMMUNICATION AND SIGNALING   8 ( 2 )   157 - 163   2014.6

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  • Connective tissue growth factor (CCN2) and microRNA-21 are components of a positive feedback loop in pancreatic stellate cells (PSC) during chronic pancreatitis and are exported in PSC-derived exosomes Reviewed

    Alyssa Charrier, Ruju Chen, Li Chen, Sherri Kemper, Takako Hattori, Masaharu Takigawa, David R. Brigstock

    JOURNAL OF CELL COMMUNICATION AND SIGNALING   8 ( 2 )   147 - 156   2014.6

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  • CCN2 as a novel molecule supporting energy metabolism of chondrocytes. Reviewed

    Maeda-Uematsu A, Kubota S, Kawaki H, Kawata K, Miyake Y, Hattori T, Nishida T, Moritani N, Lyons KM, Iida S, Takigawa M

    Journal of cellular biochemistry   115 ( 5 )   854 - 865   2014.5

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  • Differential Expression of Vascular Endothelial Growth Factor in High- and Low-Metastasis Cell Lines of Salivary Gland Adenoid Cystic Carcinoma Reviewed

    Seiji Kondo, Yoshiki Mukudai, Daisuke Soga, Takashi Nishida, Masaharu Takigawa, Tatsuo Shirota

    ANTICANCER RESEARCH   34 ( 2 )   671 - 677   2014.2

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  • Dexamethasone differentially regulates Bcl-2 family proteins in human proliferative chondrocytes: Role of pro-apoptotic Bid Reviewed

    Farasat Zaman, Dionisios Chrysis, Kirsten Huntjens, Andrei Chagin, Masaharu Takigawa, Bengt Fadeel, Lars Savendahl

    TOXICOLOGY LETTERS   224 ( 2 )   196 - 200   2014.1

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  • The regenerative effects of CCN2 independent modules on chondrocytes in vitro and osteoarthritis models in vivo Reviewed

    El Kader, Tarek Abd, Kubota Satoshi, Nishida Takashi, Hattori Takako, Aoyama Eriko, Janune Danilo, Hara Emilio S, Ono Mitsuaki, Tabata Yasuhiko, Kuboki Takuo, Takigawa Masaharu

    Bone   59   180 - 188   2014

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  • E6-AP/UBE3A Protein Acts as a Ubiquitin Ligase toward SOX9 Protein Reviewed International journal

    Hattori Takako, Kishino Tetsuya, Stephen Shelley, Eberspaecher Heidi, Maki Sayumi, Takigawa Masaharu, de Crombrugghe Benoit, Yasuda Hideyo

    JOURNAL OF BIOLOGICAL CHEMISTRY   288 ( 49 )   35138 - 35148   2013.12

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    DOI： 10.1074/jbc.M113.486795

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  • The CCN family acting throughout the body: Recent research developments Reviewed

    Satoshi Kubota, Masaharu Takigawa

    Biomolecular Concepts   4 ( 5 )   477 - 494   2013.10

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    DOI： 10.1515/bmc-2013-0018

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  • Novel role of miR-181a in cartilage metabolism. Reviewed

    Sumiyoshi K, Kubota S, Ohgawara T, Kawata K, Abd El Kader T, Nishida T, Ikeda N, Shimo T, Yamashiro T, Takigawa M

    Journal of cellular biochemistry   114 ( 9 )   2094 - 2100   2013.9

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  • CCN Family Member 2/Connective Tissue Growth Factor (CCN2/CTGF) Has Anti-Aging Effects That Protect Articular Cartilage from Age-Related Degenerative Changes Reviewed

    Itoh Shinsuke, Hattori Takako, Tomita Nao, Aoyama Eriko, Yutani Yasutaka, Yamashiro Takashi, Takigawa Masaharu

    PLOS ONE   8 ( 8 )   e71156   2013.8

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    DOI： 10.1371/journal.pone.0071156

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  • CCN2: a master regulator of the genesis of bone and cartilage Reviewed

    Masaharu Takigawa

    JOURNAL OF CELL COMMUNICATION AND SIGNALING   7 ( 3 )   191 - 201   2013.8

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  • Cartilage-Specific Over-Expression of CCN Family Member 2/Connective Tissue Growth Factor (CCN2/CTGF) Stimulates Insulin-Like Growth Factor Expression and Bone Growth Reviewed

    Tomita Nao, Hattori Takako, Itoh Shinsuke, Aoyama Eriko, Yao Mayumi, Yamashiro Takashi, Takigawa Masaharu

    PLOS ONE   8 ( 3 )   e59226   2013.3

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  • Anti-fibrotic effect of CCN3 accompanied by altered gene expression profile of the CCN family Reviewed International journal

    El Kader, Tarek Abd, Kubota Satoshi, Janune Danilo, Nishida Takashi, Hattori Takako, Aoyama Eriko, Perbal Bernard, Kuboki Takuo, Takigawa Masaharu

    JOURNAL OF CELL COMMUNICATION AND SIGNALING   7 ( 1 )   11 - 18   2013.3

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    DOI： 10.1007/s12079-012-0180-4

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  • The CCN2-inducer harmine promotes chondrogenesis and protects against TNFα-induced ablation of chondrocytic phenotype Reviewed

    Hara, E.S, M. Ono, S. Kubota, W. Sonoyama, Y. Oida, T. Hattori, T. Nishida, T. Furumatsu, T. Ozaki, M. Takigawa, T. Kuboki

    Biochimie   95   374 - 381   2013

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  • miRNA-720 Controls Stem Cell Phenotype, Proliferation and Differentiation of Human Dental Pulp Cells Reviewed

    Hara, Emilio Satoshi, Ono, Mitsuaki, Eguchi, Takanori, Kubota, Satoshi, Hai Thanh Pham, Sonoyama, Wataru, Tajima, Shoji, Takigawa, Masaharu, Calderwood, Stuart K., Kuboki, Takuo

    Plos One   8 ( 12 )   e83545   2013

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  • Novel chondrogenic and chondroprotective effects of the natural compound harmine Reviewed

    Hara, Emilio Satoshi, Ono, Mitsuaki, Kubota, Satoshi, Sonoyama, Wataru, Oida, Yasutaka, Hattori, Takako, Nishida, Takashi, Furumatsu, Takayuki, Ozaki, Toshifumi, Takigawa, Masaharu, Kuboki, Takuo

    Biochimie   95 ( 2 )   374 - 381   2013

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    DOI： 10.1016/j.biochi.2012.10.016

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  • CCN2/CTGF binds to fibroblast growth factor receptor 2 and modulates its signaling Reviewed

    Eriko Aoyama, Satoshi Kubota, Masaharu Takigawa

    FEBS LETTERS   586 ( 24 )   4270 - 4275   2012.12

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    DOI： 10.1016/j.febslet.2012.10.038

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  • Mechanical stretch increases Smad3-dependent CCN2 expression in inner meniscus cells Reviewed

    Takayuki Furumatsu, Tomoko Kanazawa, Yoshiaki Miyake, Satoshi Kubota, Masaharu Takigawa, Toshifumi Ozaki

    JOURNAL OF ORTHOPAEDIC RESEARCH   30 ( 11 )   1738 - 1745   2012.11

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    DOI： 10.1002/jor.22142

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  • Roles of heterotypic CCN2/CTGF-CCN3/NOV and homotypic CCN2-CCN2 interactions in expression of the differentiated phenotype of chondrocytes Reviewed

    Mitsuhiro Hoshijima, Takako Hattori, Eriko Aoyama, Takashi Nishida, Takashi Yamashiro, Masaharu Takigawa

    FEBS JOURNAL   279 ( 19 )   3584 - 3597   2012.10

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    DOI： 10.1111/j.1742-4658.2012.08717.x

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  • Role of LRP1 in transport of CCN2 protein in chondrocytes. Reviewed International journal

    Kawata K, Kubota S, Eguchi T, Aoyama E, Moritani NH, Kondo S, Nishida T, Takigawa M

    Journal of cell science   125 ( Pt 12 )   2965 - 2972   2012.6

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    Low-density lipoprotein receptor-related protein 1 (LRP1) is known to be a receptor for signal transmission and endocytosis. We have previously reported that LRP1 regulates WNT-β-catenin and protein kinase C signaling in chondrocytes, represses the hypertrophy of chondrocytes during endochondral ossification and that LRP1 is colocalized with a ligand, CCN family member 2 (CCN2; also known as connective tissue growth factor, CTGF), which conducts endochondral ossification, in chondrocytes. However, the role of LRP1 in the endocytic transport of CCN2 in chondrocytes is not yet understood. In the present study, we investigated the interaction between LRP1 and CCN2 during endocytic trafficking. Small interfering RNA (siRNA)-mediated knockdown of LRP1 in chondrocytic HCS-2/8 cells showed that the amount of exogenous CCN2 binding and/or incorporation was decreased in the LRP1 downregulated cells. Importantly, we observed that CCN2 internalization in chondrocytes was dependent on clathrin, and internalizated CCN2 was colocalized with an early or recycling endosome marker. Transcytosis of CCN2 through HCS-2/8 cells was confirmed by performing experiments with a trans-well apparatus, and the amount of transcytosed CCN2 was decreased by an LRP1 antagonist. These findings rule out possible leakage and confirm the crucial involvement of LRP1 during experimental transcytosis. Moreover, under hypoxic conditions that mimic the cartilaginous microenvironment, the level of LRP1 and the amount of transcytosed CCN2 increased, and these increases were neutralized by treatment with the LRP1 antagonist. The distribution of LRP1 and its antagonist in the growth plate in vivo was consistent with that of CCN2 in this tissue, which is produced by and transported by LRP1 from the chondrocytes in the prehypertrophic layer. These findings suggest that LRP1 mediates the transcytosis of CCN2, which might be a crucial event that determines the distribution of CCN2 in cartilage.

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  • A selective estrogen receptor modulator inhibits tumor necrosis factor-alpha-induced apoptosis through the ERK1/2 signaling pathway in human chondrocytes Reviewed

    Yosuke Hattori, Toshihisa Kojima, Daizo Kato, Hiroyuki Matsubara, Masaharu Takigawa, Naoki Ishiguro

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   421 ( 3 )   418 - 424   2012.5

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  • Role of low-density lipoprotein receptor related protein 1 (LRP1) in CCN2/connective tissue growth factor (CTGF) protein transport in chondrocytes

    Kawata., K, Kubota, S, Eguchi, T, Aoyama, E, Moritani, N, Kondo, S, Nishida, T, Takigawa, M

    J Cell Sci   15   2965 - 2972   2012

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  • Promotion of Ccn2 expression and osteoblastic differentiation by actin polymerization, which is induced by laminar fluid flow stress Reviewed

    Honjo T, Kubota S, Kamioka H, Sugawara Y, Ishihara Y, Yamashiro T, Takigawa M, Takano-Yamamoto T

    J Cell Commun Signal   6 ( 4 )   225 - 232   2012

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  • Induction of CCN2/CTGF by laminar fluid flow stress, which is mediated by the actin cytoskeleton in osteoblastic cells Reviewed

    Honjo, T, S. Kubota, H. Kamioka, Y. Sugawara, Y. Ishihara, T. Yamashiro, M. Takigawa, T. Takano-Yamamoto

    J Cell Commun Signal.   6   225 - 232   2012

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  • Association of the metastatic phenotype with CCN family members among breast and oral cancer cells Reviewed

    Toshihiro Ohgawara, Satoshi Kubota, Harumi Kawaki, Naito Kurio, Tarek Abd El Kader, Mitsuhiro Hoshijima, Danilo Janune, Tsuyoshi Shimo, Bernard Perbal, Akira Sasaki, Masaharu Takigawa

    JOURNAL OF CELL COMMUNICATION AND SIGNALING   5 ( 4 )   291 - 299   2011.12

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  • Novel pathogenic role of fibrin as revealed by a case study on ligneous gingivitis Reviewed

    Tsuyoshi Shimo, Akiyoshi Nishiyama, Satoshi Kubota, Naito Kurio, Tatsuo Okui, Naoki Katase, Nur Mohammad Monsur Hassan, Tatsuki Honami, Koji Kishimoto, Hiroshi Mese, Masaharu Takigawa, Akira Sasaki

    Oral Science International   8 ( 2 )   44 - 49   2011.11

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    DOI： 10.1016/S1348-8643(11)00025-5

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  • Effect of CCN2 on FGF2-Induced Proliferation and MMP9 and MMP13 Productions by Chondrocytes Reviewed

    Takashi Nishida, Satoshi Kubota, Eriko Aoyama, Danilo Janune, Azusa Maeda, Masaharu Takigawa

    ENDOCRINOLOGY   152 ( 11 )   4232 - 4241   2011.11

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    DOI： 10.1210/en.2011-0234

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  • Differential roles of CCN family proteins during osteoblast differentiation: Involvement of Smad and MAPK signaling pathways Reviewed

    Harumi Kawaki, Satoshi Kubota, Akiko Suzuki, Makoto Suzuki, Kumiko Kohsaka, Kenji Hoshi, Toshiya Fujii, Noureddine Lazar, Toshihiro Ohgawara, Takeyasu Maeda, Bernard Perbal, Teruko Takano-Yamamoto, Masaharu Takigawa

    BONE   49 ( 5 )   975 - 989   2011.11

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    DOI： 10.1016/j.bone.2011.06.033

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  • Novel effects of CCN3 that may direct the differentiation of chondrocytes Reviewed

    Danilo Janune, Satoshi Kubota, Takashi Nishida, Harumi Kawaki, Bernard Perbal, Seiji Iida, Masaharu Takigawa

    FEBS LETTERS   585 ( 19 )   3033 - 3040   2011.10

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  • The role of CCN2 in cartilage and bone development

    Satoshi Kubota, Masaharu Takigawa

    JOURNAL OF CELL COMMUNICATION AND SIGNALING   5 ( 3 )   209 - 217   2011.8

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  • CCN3-mediated promotion of sulfated proteoglycan synthesis in rat chondrocytes from developing joint heads Reviewed

    Danilo Janune, Satoshi Kubota, Noureddine Lazar, Bernard Perbal, Seiji Iida, Masaharu Takigawa

    JOURNAL OF CELL COMMUNICATION AND SIGNALING   5 ( 3 )   167 - 171   2011.8

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  • Increases in p53 expression induce CTGF synthesis by mouse and human hepatocytes and result in liver fibrosis in mice Reviewed

    Takahiro Kodama, Tetsuo Takehara, Hayato Hikita, Satoshi Shimizu, Minoru Shigekawa, Hinako Tsunematsu, Wei Li, Takuya Miyagi, Atsushi Hosui, Tomohide Tatsumi, Hisashi Ishida, Tatsuya Kanto, Naoki Hiramatsu, Satoshi Kubota, Masaharu Takigawa, Yoshito Tomimaru, Akira Tomokuni, Hiroaki Nagano, Yuichiro Doki, Masaki Mori, Norio Hayashi

    JOURNAL OF CLINICAL INVESTIGATION   121 ( 8 )   3343 - 3356   2011.8

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    DOI： 10.1172/JCI44957

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  • Mechanical stretch increases CCN2/CTGF expression in anterior cruciate ligament-derived cells Reviewed

    Yoshiaki Miyake, Takayuki Furumatsu, Satoshi Kubota, Kazumi Kawata, Toshifumi Ozaki, Masaharu Takigawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   409 ( 2 )   247 - 252   2011.6

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  • CCN Family 2/Connective Tissue Growth Factor (CCN2/CTGF) Promotes Osteoclastogenesis via Induction of and Interaction with Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) Reviewed

    Takashi Nishida, Kenji Emura, Satoshi Kubota, Karen M. Lyons, Masaharu Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   26 ( 2 )   351 - 363   2011.2

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  • Binding of glyceraldehyde-3-phosphate dehydrogenase to the cis-acting element of structure-anchored repression in ccn2 mRNA Reviewed

    Seiji Kondo, Satoshi Kubota, Yoshiki Mukudai, Takashi Nishida, Yasuto Yoshihama, Tatsuo Shirota, Satoru Shintani, Masaharu Takigawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   405 ( 3 )   382 - 387   2011.2

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  • A Coding RNA Segment That Enhances the Ribosomal Recruitment of Chicken ccn1 mRNA Reviewed

    Yoshiki Mukudai, Satoshi Kubota, Takanori Eguchi, Kumi Sumiyoshi, Danilo Janune, Seiji Kondo, Satoru Shintani, Masaharu Takigawa

    JOURNAL OF CELLULAR BIOCHEMISTRY   111 ( 6 )   1607 - 1618   2010.12

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    DOI： 10.1002/jcb.22894

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  • Design and utility of CCN2 anchor peptide aptamers

    Harumi Kawaki, Satoshi Kubota, Eriko Aoyama, Naoya Fujita, Hiroshi Hanagata, Akira Miyauchi, Kenta Nakai, Masaharu Takigawa

    BIOCHIMIE   92 ( 8 )   1010 - 1015   2010.8

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    DOI： 10.1016/j.biochi.2010.04.021

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  • Thrombopoietic-mesenchymal interaction that may facilitate both endochondral ossification and platelet maturation via CCN2

    Kumi Sumiyoshi, Satoshi Kubota, Rika A. Furuta, Kazuta Yasui, Eriko Aoyama, Harumi Kawaki, Kazumi Kawata, Toshihiro Ohgawara, Takashi Yamashiro, Masaharu Takigawa

    JOURNAL OF CELL COMMUNICATION AND SIGNALING   4 ( 1 )   5 - 14   2010.3

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  • Proinsulin C-peptide Regulates Ribosomal RNA Expression Reviewed

    Emma Lindahl, Ulrika Nyman, Farasat Zaman, Carina Palmberg, Anna Cascante, Jawed Shafqat, Masaharu Takigawa, Lars Savendahl, Hans Jorvall, Bertrand Joseph

    JOURNAL OF BIOLOGICAL CHEMISTRY   285 ( 5 )   3462 - 3469   2010.1

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  • Role of the Low-Density Lipoprotein Receptor-Related Protein-1 in Regulation of Chondrocyte Differentiation Reviewed

    Kazumi Kawata, Satoshi Kubota, Takanori Eguchi, Norifumi H. Moritani, Tsuyoshi Shimo, Seiji Kondo, Takashi Nishida, Shogo Minagi, Masaharu Takigawa

    JOURNAL OF CELLULAR PHYSIOLOGY   222 ( 1 )   138 - 148   2010.1

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  • Nicotine-induced CCN2: from Smoking to Periodontal Fibrosis Reviewed

    H. Takeuchi, S. Kubota, E. Murakashi, Y. Zhou, K. Endo, P. S. Ng, M. Takigawa, Y. Numabe

    JOURNAL OF DENTAL RESEARCH   89 ( 1 )   34 - 39   2010.1

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  • Nucleophosmin/B23: A Multifunctional Regulator that Determines the Fate of CCN2 mRNA Reviewed

    Satoshi Kubota, Yoshiki Mukudai, Harumi Kawaki, Seiji Kondo, Takanori Eguchi, Kumi Sumiyoshi, Toshihiro Ohgawara, Tsuyoshi Shimo, Masaharu Takigawa

    CCN PROTEINS IN HEALTH AND DISEASE: AN OVERVIEW OF THE FIFTH INTERNATIONAL WORKSHOP ON THE CCN FAMILY OF GENES   41 - +   2010

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    DOI： 10.1007/978-90-481-3779-4_4

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  • Cooperative Regulation of Cell Proliferation and Differentiation by CCN2 and CCN3 Reviewed

    Masaharu Takigawa, Harumi Kawaki, Satoshi Kubota, Karen M. Lyons, Bernard Perbal

    CCN PROTEINS IN HEALTH AND DISEASE: AN OVERVIEW OF THE FIFTH INTERNATIONAL WORKSHOP ON THE CCN FAMILY OF GENES   105 - +   2010

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  • 結合組織成長因子(CTGF/CCN2)と軟骨形成 Invited

    久保田聡, 滝川正春

    骨粗鬆症治療   9 ( 4 )   287 - 290   2010

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  • Identification of miR-1 as a micro RNA that supports late-stage differentiation of growth cartilage cells Reviewed

    Sumiyoshi K, Kubota S, Ohgawara T, Kawata K, Nishida T, Shimo T, Yamashiro T, Takigawa M

    Biochemical and Biophysical Research Communications   402 ( 2 )   286 - 290   2010

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    DOI： 10.1016/j.bbrc.2010.10.016

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  • Novel Transcriptional Regulation of CCN2/CTGF by Nuclear Translocation of MMP3 Reviewed

    Takanori Eguchi, Satoshi Kubota, Kazumi Kawata, Yoshiki Mukudai, Junji Uehara, Toshihiro Ohgawara, Soichiro Ibaragi, Akira Sasaki, Takuo Kuboki, Masaharu Takigawa

    CCN PROTEINS IN HEALTH AND DISEASE: AN OVERVIEW OF THE FIFTH INTERNATIONAL WORKSHOP ON THE CCN FAMILY OF GENES   255 - +   2010

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  • CCN proteins in health and disease: An overview of the fifth international workshop on the CCN family of genes

    Annick Perbal, Masaharu Takigawa, Bernard Perbal

    CCN Proteins in Health and Disease: An Overview of the Fifth International Workshop on the CCN Family of Genes   1 - 338   2010

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    DOI： 10.1007/978-90-481-3779-4

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  • 低密度リポタンパク受容体関連タンパク-1(LRP1)の軟骨細胞分化における多面的作用機構

    河田 かずみ, 久保田 聡, 江口 傑徳, 青山 絵理子, 森谷 徳文, 近藤 誠二, 西田 崇, 皆木 省吾, 滝川 正春

    日本生化学会大会プログラム・講演要旨集   82回   4T4p - 9   2009.9

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  • All-trans retinoic acid-induced ADAM28 degrades proteoglycans in human chondrocytes Reviewed

    Yuichi Hikichi, Koji Yoshimura, Masaharu Takigawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   386 ( 2 )   294 - 299   2009.8

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    DOI： 10.1016/j.bbrc.2009.06.052

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  • N-terminal domains of CCN family 2/connective tissue growth factor bind to aggrecan Reviewed

    Eriko Aoyama, Takako Hattori, Mitsuhiro Hoshijima, Daisuke Araki, Takashi Nishida, Satoshi Kubota, Masaharu Takigawa

    BIOCHEMICAL JOURNAL   420   413 - 420   2009.6

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    DOI： 10.1042/BJ20081991

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  • CTGF and Apoptosis in Mouse Osteocytes Induced by Tooth Movement

    Y. Sakai, T. A. Balam, S. Kuroda, N. Tamamura, T. Fukunaga, M. Takigawa, T. Takano-Yamamoto

    JOURNAL OF DENTAL RESEARCH   88 ( 4 )   345 - 350   2009.4

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  • Effect of transforming growth factor-beta1 on expression of the connective tissue growth factor (CCN2/CTGF) gene in normal human gingival fibroblasts and periodontal ligament cells Reviewed

    H. Takeuchi, S. Kubota, E. Murakashi, T. Fukada, S. Hashimoto, M. Takigawa, Y. Numabe

    JOURNAL OF PERIODONTAL RESEARCH   44 ( 2 )   161 - 169   2009.4

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    DOI： 10.1111/j.1600-0765.2008.01093.x

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  • Regulation of chondrocytic phenotype by micro RNA 18a: Involvement of Ccn2/Ctgf as a major target gene

    Toshihiro Ohgawara, Satoshi Kubota, Harumi Kawaki, Seiji Kondo, Takanori Eguchi, Naito Kurio, Eriko Aoyama, Akira Sasaki, Masaharu Takigawa

    FEBS LETTERS   583 ( 6 )   1006 - 1010   2009.3

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    DOI： 10.1016/j.febslet.2009.02.025

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  • CCN Family 2/Connective Tissue Growth Factor Modulates BMP Signalling as a Signal Conductor, Which Action Regulates the Proliferation and Differentiation of Chondrocytes

    Azusa Maeda, Takashi Nishida, Eriko Aoyama, Satoshi Kubota, Karen M. Lyons, Takuo Kuboki, Masaharu Takigawa

    JOURNAL OF BIOCHEMISTRY   145 ( 2 )   207 - 216   2009.2

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  • CCN family 2/connective tissue growth factor (CCN2/CFGF) regulates the expression of Vegf through Hif-1 alpha expression in a chondrocytic cell line, HCS-2/8, under hypoxic condition

    Takashi Nishida, Seiji Kondo, Azusa Maeda, Satoshi Kubota, Karen M. Lyons, Masaharu Takigawa

    BONE   44 ( 1 )   24 - 31   2009.1

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    DOI： 10.1016/j.bone.2008.08.125

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  • Cooperative Regulation of Chondrocyte Differentiation by CCN2 and CCN3 Shown by a Comprehensive Analysis of the CCN Family Proteins in Cartilage

    Harumi Kawaki, Satoshi Kubota, Akiko Suzuki, Noureddine Lazar, Tomohiro Yamada, Tatsushi Matsumura, Toshihiro Ohgawara, Takeyasu Maeda, Bernard Perbal, Karen M. Lyons, Masaharu Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   23 ( 11 )   1751 - 1764   2008.11

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    DOI： 10.1359/JBMR.080615

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  • 低密度リポタンパク受容体関連タンパク-1(LRP1)の軟骨細胞分化における機能とその作用機構

    河田 かずみ, 久保田 聡, 江口 傑徳, 青山 絵理子, 皆木 省吾, 滝川 正春

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   81回・31回   4T13 - 2   2008.11

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  • Posttranscriptional regulation of chicken ccn2 gene expression by nucleophosmin/B23 during chondrocyte differentiation

    Yoshiki Mukudai, Satoshi Kubota, Harumi Kawaki, Seiji Kondo, Takanori Eguchi, Kumi Sumiyoshi, Toshihiro Ohgawara, Tsuyoshi Shimo, Masaharu Takigawa

    MOLECULAR AND CELLULAR BIOLOGY   28 ( 19 )   6134 - 6147   2008.10

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    DOI： 10.1128/MCB.00495-08

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  • 軟骨細胞分化における低密度リポタンパク受容体関連タンパク-1(LRP1)の関与

    河田 かずみ, 久保田 聡, 江口 傑徳, 青山 絵理子, 皆木 省吾, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   26回   234 - 234   2008.10

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  • Distribution, gene expression, and functional role of EphA4 during ossification

    Chisa Kuroda, Satoshi Kubota, Kazumi Kawata, Eriko Aoyama, Kumi Sumiyoshi, Morihiko Oka, Miho Inoue, Shogo Minagi, Masaharu Takigawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   374 ( 1 )   22 - 27   2008.9

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    DOI： 10.1016/j.bbrc.2008.06.089

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  • Increased expression of matrilin-3 not only in osteoarthritic articular cartilage but also in cartilage-forming tumors, and down-regulation of SOX9 via epidermal growth factor domain 1-dependent signaling

    Jean-Baptiste Vincourt, Jean-Michel Vignaud, Frederic Lionneton, Francois Sirveaux, Harumi Kawaki, Sophie Marchal, Sandra Lomazzi, Francois Plenat, Francois Guillemin, Patrick Netter, Masaharu Takigawa, Didier Mainard, Jacques Magdalou

    ARTHRITIS AND RHEUMATISM   58 ( 9 )   2798 - 2808   2008.9

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    DOI： 10.1002/art.23761

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  • Induction of hepatocyte growth factor expression by maleic acid in human fibroblasts through MAPK activation

    Takahiro Motoki, Yoshihiro Sugiura, Yohsuke Matsumoto, Tomoe Tsuji, Satoshi Kubota, Masaharu Takigawa, Eiichi Gohda

    JOURNAL OF CELLULAR BIOCHEMISTRY   104 ( 4 )   1465 - 1476   2008.7

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    DOI： 10.1002/jeb.21724

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  • CCN family 2/connective tissue growth factor (CCN2/CTGF) stimulates proliferation and differentiation of auricular chondrocytes

    T. Fujisawa, T. Hattori, M. Ono, J. Uehara, S. Kubota, T. Kuboki, M. Takigawa

    OSTEOARTHRITIS AND CARTILAGE   16 ( 7 )   787 - 795   2008.7

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    DOI： 10.1016/j.joca.2007.11.001

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  • Clinical significance and pathogenic function of connective tissue growth factor (CTGF/CCN2) in osteolytic mandibular squamous cell carcinoma

    Tsuyoshi Shimo, Satoshi Kubota, Takeshi Goda, Yasuto Yoshihama, Naito Kurio, Takashi Nishida, Poh-Sing Ng, Koki Endo, Masaharu Takigawa, Akira Sasaki

    ANTICANCER RESEARCH   28 ( 4C )   2343 - 2348   2008.7

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  • Promotion of bone regeneration by CCN2 incorporated into gelatin hydrogel

    Takeshi Kikuchi, Satoshi Kubota, Koji Asaumi, Harumi Kawaki, Takashi Nishida, Kazumi Kawata, Shigeru Mitani, Yasuhiko Tabata, Toshifumi Ozaki, Masaharu Takigawa

    TISSUE ENGINEERING PART A   14 ( 6 )   1089 - 1098   2008.6

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    DOI： 10.1089/ten.tea.2007.0167

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  • CCN2遺伝子関連ノンコーディングRNAの軟骨細胞様HCS-2/8細胞における発現

    大河原 敏博, 久保田 聡, 川木 晴美, 近藤 誠二, 佐々木 朗, 滝川 正春

    岡山歯学会雑誌   27 ( 1 )   63 - 63   2008.6

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  • CCNファミリー2/結合組織成長因子(CCN2/CTGF)が骨芽細胞において骨形成因子(BMP)-2刺激による骨芽細胞分化を修飾する

    前田 あずさ, 西田 崇, 川木 晴美, 久保田 聡, 窪木 拓男, 滝川 正春

    岡山歯学会雑誌   27 ( 1 )   63 - 64   2008.6

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  • Transcriptional regulation of chondrogenesis by coactivator Tip60 via chromatin association with Sox9 and Sox5

    Takako Hattori, Francoise Coustry, Shelley Stephens, Heidi Eberspaecher, Masaharu Takigawa, Hideyo Yasuda, Benoit de Crombrugghe

    NUCLEIC ACIDS RESEARCH   36 ( 9 )   3011 - 3024   2008.5

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    DOI： 10.1093/nar/gkn150

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  • Interleukin-4 downregulates the cyclic tensile stress-induced matrix metalloproteinases-13 and cathepsin B expression by rat normal chondrocytes

    Hideyuki Doi, Keiichiro Nishida, Masanori Yorimitsu, Takamitsu Komiyama, Yasutaka Kadota, Tomonori Tetsunaga, Aki Yoshida, Satoshi Kubota, Masaharu Takigawa, Toshifumi Ozaki

    ACTA MEDICA OKAYAMA   62 ( 2 )   119 - 126   2008.4

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  • Connective tissue growth factor is overexpressed in muscles of human muscular dystrophy

    Guilian Sun, Kazuhiro Haginoya, Yanling Wu, Yoko Chiba, Tohru Nakanishi, Akira Onuma, Yuko Sato, Masaharu Takigawa, Kazuie Iinuma, Shigeru Tsuchiya

    JOURNAL OF THE NEUROLOGICAL SCIENCES   267 ( 1-2 )   48 - 56   2008.4

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    DOI： 10.1016/j.jns.2007.09.043

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  • Effects of alendronate and pamidronate on cultured rat metatarsal bones: Failure to prevent dexamethasone-induced growth retardation

    Terhi J. Heino, Andrei S. Chagin, Masaharu Takigawa, Lars Savendahl

    BONE   42 ( 4 )   702 - 709   2008.4

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    DOI： 10.1016/j.bone.2008.01.001

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  • Novel transcription factor-like function of human matrix metalloproteinase 3 regulating the CTGF/CCN2 gene

    Takanori Eguchi, Satoshi Kubota, Kazumi Kawata, Yoshiki Mukudai, Junji Uehara, Toshihiro Ohgawara, Soichiro Ibaragi, Akira Sasaki, Takuo Kuboki, Masaharu Takigawa

    MOLECULAR AND CELLULAR BIOLOGY   28 ( 7 )   2391 - 2413   2008.4

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    DOI： 10.1128/MCB.01288-07

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  • Plasma connective tissue growth factor is a novel potential biomarker of cardiac dysfunction in patients with chronic heart failure

    Norimichi Koitabashi, Masashi Arai, Kazuo Niwano, Atai Watanabe, Michiko Endoh, Masahiko Suguta, Tomoyuki Yokoyama, Hiroshi Tada, Takuji Toyama, Hitoshi Adachi, Shigeto Naito, Shigeru Oshima, Takashi Nishida, Satoshi Kubota, Masaharu Takigawa, Masahiko Kurabayashi

    EUROPEAN JOURNAL OF HEART FAILURE   10 ( 4 )   373 - 379   2008.4

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    DOI： 10.1016/j.ejheart.2008.02.011

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  • Functional requirement of CCN2 for intramembranous bone formation in embryonic mice

    Harumi Kawaki, Satoshi Kubota, Akiko Suzuki, Tomohiro Yamada, Tatsushi Matsumura, Toshiko Mandal, Mayumi Yao, Takeyasu Maeda, Karen M. Lyons, Masaharu Takigawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   366 ( 2 )   450 - 456   2008.2

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    DOI： 10.1016/j.bbrc.2007.11.155

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  • Inhibition of tumor-stromal interaction through HGF/Met signaling by valproic acid

    Yohsuke Matsumoto, Takahiro Motoki, Satoshi Kubota, Masaharu Takigawa, Hirohito Tsubouchi, Eiichi Gohda

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   366 ( 1 )   110 - 116   2008.2

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    DOI： 10.1016/j.bbrc.2007.11.089

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  • Effects of tensile and compressive strains on response of a chondrocytic cell line embedded in type I collagen gel

    Yuji Hirano, Naoki Ishiguro, Masahiro Sokabe, Masaharu Takigawa, Keiji Naruse

    JOURNAL OF BIOTECHNOLOGY   133 ( 2 )   245 - 252   2008.1

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    DOI： 10.1016/j.jbiotee.2007.07.955

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  • Role of mechanical-stress inducible protein Hcs24/CTGF/CCN2 in cartilage growth and regeneration: Mechanical stress induces expression of Hcs24/CTGF/CCN2 in a human chondrocytic cell line HCS-2/8, rabbit costal chondrocytes and meniscus tissue cells

    Takashi Nishida, Azusa Maeda, Satoshi Kubota, Masaharu Takigawa

    BIORHEOLOGY   45 ( 3-4 )   289 - 299   2008

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    DOI： 10.3233/BIR-2008-0478

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  • Promotion of hydroxyapatite-associated, stem cell-based bone regeneration by CCN2

    Mitsuaki Ono, Satoshi Kubota, Takuo Fujisawa, Wataru Sonoyama, Harumi Kawakij, Kentaro Akiyama, Kengo Shimono, Masarnitsu Oshima, Takashi Nishida, Yasuhiro Yoshida, Kazuomi Suzuki, Masaharu Takigawa, Takuo Kuboki

    CELL TRANSPLANTATION   17 ( 1-2 )   231 - 240   2008

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    DOI： 10.3727/000000008783907143

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  • Gene expression and distribution of connective tissue growth factor (CCN2/CTGF) during secondary ossification center formation

    Morihiko Oka, Satoshi Kubota, Seiji Kondo, Takanori Eguchi, Chisa Kuroda, Kazumi Kawata, Shogo Minagi, Masaharu Takigawa

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY   55 ( 12 )   1245 - 1255   2007.12

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    DOI： 10.1369/jhc.7A7263.2007

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  • Proteasome inhibition up-regulates p53 and apoptosis-inducing factor in chondrocytes causing severe growth retardation in mice

    Farasat Zaman, Victoria Menendez-Benito, Emma Eriksson, Andrei S. Chagin, Masaharu Takigawa, Bengt Fadeel, Nico P. Dantuma, Dionisios Chrysis, Lars Saevendahl

    CANCER RESEARCH   67 ( 20 )   10078 - 10086   2007.10

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    DOI： 10.1158/0008-5472.CAN-06-3982

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  • CCN2 (Connective Tissue Growth Factor) is essential for extracellular matrix production and integrin signaling in chondrocytes

    Takashi Nishida, Harumi Kawaki, Ruth M. Baxter, R. Andrea DeYoung, Masaharu Takigawa, Karen M. Lyons

    JOURNAL OF CELL COMMUNICATION AND SIGNALING   1 ( 1 )   45 - 58   2007.6

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    DOI： 10.1007/s12079-007-0005-z

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  • Report on the fourth international workshop on the CCN family of genes

    S. Kubota, H. Yeger, B. Perbal, M. Takigawa

    JOURNAL OF CELL COMMUNICATION AND SIGNALING   1 ( 1 )   59 - 65   2007.6

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    DOI： 10.1007/s12079-007-0002-2

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  • Tamoxifen induces permanent growth arrest through selective induction of apoptosis in growth plate chondrocytes in cultured rat metatarsal bones

    Andrei S. Chagin, Elham Karimian, Farasat Zaman, Masaharu Takigawa, Dionisios Chrysis, Lars Savendahl

    BONE   40 ( 5 )   1415 - 1424   2007.5

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    DOI： 10.1016/j.bone.2006.12.066

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  • Promotion of attachment of human bone marrow stromal cells by CCN2

    Mitsuaki Ono, Satoshi Kubota, Takuo Fujisawa, Wataru Sonoyama, Harumi Kawaki, Kentaro Akiyama, Masamitsu Oshima, Takashi Nishida, Yasuhlro Yoshida, Kazuomi Suzuki, Masaharu Takigawa, Takuo Kuboki

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   357 ( 1 )   20 - 25   2007.5

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    DOI： 10.1016/j.bbrc.2007.03.052

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  • Increased connective tissue growth factor relative to brain natriuretic peptide as a determinant of myocardial fibrosis

    Norimichi Koitabashi, Masashi Arai, Shinya Kogure, Kazuo Niwano, Atai Watanabe, Yasuhiro Aoki, Toshitaka Maeno, Takashi Nishida, Satoshi Kubota, Masaharu Takigawa, Masahiko Kurabayashi

    HYPERTENSION   49 ( 5 )   1120 - 1127   2007.5

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    DOI： 10.1161/HYPERTENSIONAHA.106.077537

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  • Expression and physiological role of CCN4/Wnt-induced secreted protein 1 mRNA splicing variants in chondrocytes

    Takeshi Yanagita, Satoshi Kubota, Harumi Kawaki, Kazumi Kawata, Seiji Kondo, Teruko Takano-Yamamoto, Shinji Tanaka, Masaharu Takigawa

    FEBS JOURNAL   274 ( 7 )   1655 - 1665   2007.4

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    DOI： 10.1111/j.1742-4658.2007.05709.x

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  • A functional polymorphism in the 5 ' UTR of GDF5 is associated with susceptibility to osteoarthritis

    Yoshinari Miyamoto, Akihiko Mabuchi, Dongquan Shi, Toshikazu Kubo, Yoshio Takatori, Susumu Saito, Mikihiro Fujioka, Akihiro Sudo, Atsumasa Uchida, Seizo Yamamoto, Koichi Ozaki, Masaharu Takigawa, Toshihiro Tanaka, Yusuke Nakamura, Qing Jiang, Shiro Ikegawa

    NATURE GENETICS   39 ( 4 )   529 - 533   2007.4

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    DOI： 10.1038/ng2005

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  • Different transcriptional strategies for ccn2/ctgf gene induction between human chondrocytic and breast cancer cell lines

    Takanori Eguchi, Satoshi Kubota, Kazumi Kawata, Yoshiki Mukudai, Toshihiro Ohgawara, Kohei Miyazono, Kyouji Nakao, Seiji Kondo, Masaharu Takigawa

    BIOCHIMIE   89 ( 3 )   278 - 288   2007.3

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    DOI： 10.1016/j.biochi.2006.12.006

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  • CCN family proteins and angiogenesis: From embryo to adulthood

    Satoshi Kubota, Masaharu Takigawa

    Angiogenesis   10 ( 1 )   1 - 11   2007.3

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  • Prostaglandin E-2 downregulates TNF-alpha-induced production of matrix metalloproteinase-1 in HCS-2/8 chondrocytes by inhibiting Raf-1/MEK/ERK cascade through EP4 prostanoid receptor activation

    Kazunari Fushimi, Shigeru Nakashima, Fukka You, Masaharu Takigawa, Katsuji Shimizu

    JOURNAL OF CELLULAR BIOCHEMISTRY   100 ( 3 )   783 - 793   2007.2

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    DOI： 10.1002/jcb.21099

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  • Dopamine Receptor Presence in the Rat Area Postrema Identified by RT-PCR, Immunohistochemistry, and In Situ Hybridization

    Izawa Shunji, Yamaai Tomoichiro, Mukudai Yoshiki, Yamaji Kozo, Nishitani Yoshihiro, Itota Toshiyuki, Matsuo Ryuji, Takigawa Masaharu, Yoshiyama Masahiro

    Japanese Journal of Oral Biology   49 ( 4 )   259 - 268   2007

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    Dopamine (DA) is a major central nervous system (CNS) neurotransmitter with many important physiological activities. Investigations into the neuroanatomy and neurologic functions of the dopaminergic neural systems have generated much debate. Regarding neuroanatomy, physiological and pharmacological criteria have divided DA receptors into D1 and D2 subtypes. The genes encoding these subtypes have been cloned and classified into a D1 subfamily encompassing D1 and D5 receptors and a D2 subfamily with D2, D3, and D4. Based on the sequences of the cloned receptors, we prepared antibodies and riboprobes to elucidate the expression of the corresponding proteins and mRNAs in the rat area postrema (AP) by immunohistochemistry and in situ hybridization (ISH). The AP was obtained from adult male Sprague-Dawley rats undergoing brain surgery, and tissue samples were used for RT-PCR, immunohistochemistry, and ISH. The results showed that D2 and D5 receptors and their mRNAs exist in the rat AP. On the other hand, D1, D3, and D4 receptors and their mRNAs were not detected.

    DOI： 10.2330/joralbiosci.49.259

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  • 結合組織成長因子CTGF/CCN2 Invited

    服部高子, 久保田聡, 滝川正春

    The Lung perspectives   15 ( 3 )   331 - 335   2007

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  • Role of CCN2/CTGF/Hcs24 in bone growth Reviewed

    Satoshi Kubota, Masaharu Takigawa

    INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 257   257   1 - 41   2007

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    DOI： 10.1016/S0074-7696(07)57001-4

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  • Multiple activation of mitogen-activated protein kinases by purified independent CCN2 modules in vascular endothelial cells and chondrocytes in culture

    S. Kubota, H. Kawaki, S. Kondo, G. Yosimichi, M. Minato, T. Nishida, H. Hanagata, A. Miyauchi, M. Takigawa

    BIOCHIMIE   88 ( 12 )   1973 - 1981   2006.12

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    DOI： 10.1016/j.biochi.2006.07.007

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  • Expression of neurotrophins and their receptors tropomyosin-related kinases (Trk) under tension-stress during distraction osteogenesis

    Ayako Aiga, Koji Asaumi, You-Jin Lee, Hiroaki Kadota, Shigeru Mitani, Toshifumi Ozaki, Masaharu Takigawa

    ACTA MEDICA OKAYAMA   60 ( 5 )   267 - 277   2006.10

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  • [Autoantigen and molecular chaperone in rheumatoid arthritis--their roles in metabolism of chondrocytes]. Reviewed

    Hattori T, Takigawa M

    Clinical calcium   16 ( 9 )   1553 - 1556   2006.9

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    The endoplasmic reticulum chaperone; heat shock protein/rheumatoid arthritis-related antigen (HSP47/RA-A47), in addition to its important intercellular functions for collagen maturation and secretion, has chondrocytes-destructive roles such as induction of endoplasmic reticulum (ER)-stress and metabolic gene expressions result in apoptosis when HSP47/RA-A47 is downregulated. Extracellular HSP47/RA-A47 may act as an autoantigen, but also regulate autoimmune inflammation. It is, therefore, a potential new biologic therapy for rheumatoid arthritis.

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  • 硬組織モジュレーターCCN/CTGFのIGFBPモジュレーターを介した軟骨細胞増殖・分化促進効果

    川木 晴美, 久保田 聡, 湊 雅直, 近藤 誠二, 滝川 正春

    Journal of Oral Biosciences   48 ( Suppl. )   113 - 113   2006.9

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  • Pathogenic role of connective tissue growth factor (CTGF/CCN2) in osteolytic metastasis of breast cancer

    T Shimo, S Kubota, N Yoshioka, S Ibaragi, S Isowa, T Eguchi, A Sasaki, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   21 ( 7 )   1045 - 1059   2006.7

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    DOI： 10.1359/JBMR.060416

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  • 結合組織成長因子CCN2/CTGFによる骨髄由来間質細胞の細胞接着、遊走の亢進とシグナル伝達経路の活性化

    大野 充昭, 藤澤 拓生, 久保田 聡, 園山 亘, 秋山 謙太郎, 西田 崇, 滝川 正春, 窪木 拓男

    日本骨代謝学会学術集会プログラム抄録集   24回   248 - 248   2006.7

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  • Possible role of LRP1, a CCN2 receptor, in chondrocytes

    K Kawata, T Eguchi, S Kubota, H Kawaki, M Oka, S Minagi, M Takigawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   345 ( 2 )   552 - 559   2006.6

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    DOI： 10.1016/j.bbrc.2006.04.109

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  • Roles of PKC, PI3K and JNK in multiple transduction of CCN2/CTGF signals in chondrocytes

    G Yosimichi, S Kubota, T Nishida, S Kondo, T Yanagita, K Nakao, T Takano-Yamamoto, M Takigawa

    BONE   38 ( 6 )   853 - 863   2006.6

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    DOI： 10.1016/j.bone.2005.11.016

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  • Dexamethasone induces connective tissue growth factor expression in renal tubular epithelial cells in a mouse strain-specific manner

    H Okada, T Kikuta, T Inoue, Y Kanno, S Ban, T Sugaya, M Takigawa, H Suzuki

    AMERICAN JOURNAL OF PATHOLOGY   168 ( 3 )   737 - 747   2006.3

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    DOI： 10.2353/ajpath.2006.050656

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  • Transcriptional regulation of the cartilage intermediate layer protein (CILP) gene Reviewed

    M Mori, M Nakajima, Y Mikami, S Seki, M Takigawa, T Kubo, S Ikegawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   341 ( 1 )   121 - 127   2006.3

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    DOI： 10.1016/j.bbrc.2005.12.159

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  • Locally produced estrogen promotes fetal rat metatarsal bone growth; an effect mediated through increased chondrocyte proliferation and decreased apoptosis

    AS Chagin, D Chrysis, M Takigawa, EM Ritzen, L Savendahl

    JOURNAL OF ENDOCRINOLOGY   188 ( 2 )   193 - 203   2006.2

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    DOI： 10.1677/joe.1.06364

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  • Hypoxic regulation of stability of connective tissue growth factor/CCN2 mRNA by 3 '-untranslated region interacting with a cellular protein in human chondrosarcoma cells

    S Kondo, S Kubota, Y Mukudai, N Moritani, T Nishida, H Matsushita, S Matsumoto, T Sugahara, M Takigawa

    ONCOGENE   25 ( 7 )   1099 - 1110   2006.2

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    DOI： 10.1038/sj.onc.1209129

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  • CT domain of CCN2/CTGF directly interacts with fibronectin and enhances cell adhesion of chondrocytes through integrin alpha 5 beta 1

    M Hoshijima, T Hattori, M Inoue, D Araki, H Hanagata, A Miyauchi, M Takigawa

    FEBS LETTERS   580 ( 5 )   1376 - 1382   2006.2

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    DOI： 10.1016/j.febslet.2006.01.061

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  • Cartducin, a paralog of Acrp30/adiponectin, is induced during chondrogenic differentiation and promotes proliferation of chondrogenic precursors and chondrocytes

    T Maeda, A Jikko, M Abe, T Yokohama-Tamaki, H Akiyama, S Furukawa, M Takigawa, S Wakisaka

    JOURNAL OF CELLULAR PHYSIOLOGY   206 ( 2 )   537 - 544   2006.2

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    DOI： 10.1002/jcp.20493

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  • Novel angiogenic inhibitor DN-9693 that inhibits post-transcriptional induction of connective tissue growth factor (CTGF/CCN2) by vascular endothelial growth factor in human endothelial cells

    S Kondo, N Tanaka, S Kubota, Y Mukudai, G Yosimichi, T Sugahara, M Takigawa

    MOLECULAR CANCER THERAPEUTICS   5 ( 1 )   129 - 137   2006.1

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    DOI： 10.1158/1535-7163.MCT-05-0097

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  • 軟骨組織の発生分化とCCNファミリー遺伝子

    久保田聡, 滝川正春

    Clinical Calcium   16,486-492   2006

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  • 関節リウマチにおける自己抗原と分子シャペロン?軟骨細胞におけるその役割

    服部高子, 滝川正春

    Clinical Calcium   16,1553-1556 ( 9 )   1553 - 1556   2006

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  • Expression and regulation of an antisense RNA transcript of the human connective tissue growth factor gene in human tumour cells

    Seiji Kondo, Satoshi Kubota, Harumi Kawaki, Norifumi Moritani, Toshimasa Kagawa, Takaaki Ueno, Toshio Sugahara, Masaharu Takigawa

    Asian Journal of Oral and Maxillofacial Surgery   18 ( 3 )   172 - 179   2006

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    DOI： 10.1016/S0915-6992(06)80014-2

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  • Effect of connective tissue growth factor (CCN2/CTGF) on proliferation and differentiation of mouse periodontal ligament-derived cells

    Masahiro Asano, Satoshi Kubota, Tohru Nakanishi, Takashi Nishida, Tomoichiro Yamaai, Gen Yosimichi, Kazumi Ohyama, Tomosada Sugimoto, Yoji Murayama, Masaharu Takigawa

    Cell Communication and Signaling   3   11(Epub)   2005.10

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    DOI： 10.1186/1478-811X-3-11

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  • The human chondrosarcoma HCS-2/8 cell line is responsive to BMP-7, but not to IL-1beta

    J Saas, M Gebauer, C Jacobi, J Haag, M Takigawa, T Aigner

    FRONTIERS IN BIOSCIENCE   10   2027 - 2035   2005.9

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  • 軟骨細胞におけるCCN familyメンバーのdexahamethasoneによる遺伝子発現調節

    川木 晴美, 久保田 聡, 近藤 誠二, 滝川 正春

    Journal of Oral Biosciences   47 ( Suppl. )   86 - 86   2005.9

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  • 新規血管新生阻害剤DN-9693の作用機序 VEGFによる血管新生因子CTGF/CCN2の発現レベルの上昇に対する阻害効果

    近藤 誠二, 田中 紀子, 久保田 聡, 菅原 利夫, 滝川 正春

    日本癌学会総会記事   64回   134 - 134   2005.9

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  • ヒト軟骨肉腫由来軟骨細胞株 (HCS-2/8)におけるWnt誘導分泌タンパク質1 (Wisp1/CCN4)mRNAスプライス変異体(Writ-induced secreted protein 1(Wispl/CCN4) mRNA splicing variants in a human chondrosarcoma-derived chondrocytic cell line (HCS-2/8))

    Yanagita Takeshi, Kubota Satoshi, Hattori Takako, Hoshijima Mitsuhiro, Kawata Kazumi, Takano-Yamamoto Teruko, Takigawa Masaharu

    生化学   77 ( 8 )   1014 - 1014   2005.8

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  • Gene expression of connective tissue growth factor (CTGF/CCN2) in calcifying tissues of normal and cbfa1-null mutant mice in late stage of embryonic development

    T Yamaai, T Nakanishi, M Asano, K Nawachi, G Yoshimichi, K Ohyama, T Komori, T Sugimoto, M Takigawa

    JOURNAL OF BONE AND MINERAL METABOLISM   23 ( 4 )   280 - 288   2005.7

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    DOI： 10.1007/s00774-004-0600-5

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  • Translational repression by the cis-acting element of structure-anchored repression (CAESAR) of human ctgf/ccn2 mRNA

    S Kubota, Y Mukudai, NH Moritani, K Nakao, K Kawata, M Takigawa

    FEBS LETTERS   579 ( 17 )   3751 - 3758   2005.7

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    DOI： 10.1016/j.febslet.2005.05.068

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  • CONNECTIVE TISSUE GROWTH FACTOR MEDIATES PROFIBROTIC EFFECTS OF TRANSFORMING GROWTH FACTOR-B PRODUCED BY TUBULAR EPITHELIAL CELLS IN RESPONSE TO HIGH GLUCOSE

    Nobutaka Kato, Hirokazu Okada, Tatsuya Kobayashi, Tsutomu Inoue, Tomohiro Kikuta, Yoshihiko Kanno, Yusuke Watanabe, Soichi Sugahara, Hitoshi Hoshi, Keita Sueyoshi, Hiromichi Suzuki

    NEPHROLOGY   10   A24 - A24   2005.6

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  • 二次骨化中心形成過程に発現する結合組織成長因子CTGF/CCN2のパールカン陽性軟骨細胞への特異的集積

    岡 森彦, 久保田 聡, 近藤 誠二, 江口 傑徳, 河田 かずみ, 黒田 知沙, 皆木 省吾, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   23回   229 - 229   2005.6

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  • 低酸素組織,軟骨における肥大軟骨特異的蛋白24/結合組織成長因子/CCNファミリー2mRNAの安定化機構 核および細胞質タンパク結合を介した3'-非翻訳領域(UTR)の関与

    近藤 誠二, 久保田 聡, 椋代 義樹, 森谷 徳文, 西田 崇, 菅原 利夫, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   23回   159 - 159   2005.6

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  • 結合組織成長因子CCN2/CTGF/Hcs24はヒト骨髄由来間質細胞の細胞接着を促進させる

    大野 充昭, 園山 亘, 藤澤 拓生, 秋山 謙太郎, 前川 賢治, 完山 学, 西田 崇, 久保田 聡, 滝川 正春, 窪木 拓男

    日本骨代謝学会学術集会プログラム抄録集   23回   225 - 225   2005.6

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  • 軟骨由来多機能成長因子CCN2/CTGF/Hcs24は耳介軟骨細胞の形質発現を増強する

    藤澤 拓生, 中尾 匡志, 服部 高子, 久保田 聡, 窪木 拓男, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   23回   262 - 262   2005.6

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  • 軟骨細胞における低密度リポタンパク受容体関連タンパク1(LRP1)の遺伝子発現とタンパク質局在

    河田 かずみ, 江口 傑徳, 久保田 聡, 川木 晴美, 岡 森彦, 皆木 省吾, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   23回   260 - 260   2005.6

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  • 各種軟骨細胞におけるM-CSFの産生とその生理的役割

    中尾 匡志, 久保田 聡, 藤澤 拓生, 岡 森彦, 江口 傑徳, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   23回   177 - 177   2005.6

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  • Connective tissue growth factor causes persistent pro alpha 2(l) collagen gene expression induced by transforming growth factor-beta in a mouse fibrosis model

    S Chujo, F Shirasaki, S Kawara, Y Inagaki, T Kinbara, M Inaoki, M Takigawa, K Takehara

    JOURNAL OF CELLULAR PHYSIOLOGY   203 ( 2 )   447 - 456   2005.5

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    DOI： 10.1002/jcp.20251

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  • Collaborative action of M-CSF and CTGF/CCN2 in articular chondrocytes: Possible regenerative roles in articular cartilage metabolism

    K Nakao, S Kubota, H Doi, T Eguchi, M Oka, T Fujisawa, T Nishida, M Takigawa

    BONE   36 ( 5 )   884 - 892   2005.5

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    DOI： 10.1016/j.bone.2004.10.015

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  • Comparable response of ccn1 with ccn2 genes upon arthritis: An in vitro evaluation with a human chondrocytic cell line stimulated by a set of cytokines

    Norifumi H. Moritani, Satoshi Kubota, Toshio Sugahara, Masaharu Takigawa

    Cell Communication and Signaling   3   6 - e-Pub   2005.4

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    DOI： 10.1186/1478-811X-3-6

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  • Methylation status of EXT1 and EXT2 promoters and two mutations of EXT2 in chondrosarcoma

    T Tsuchiya, T Osanai, A Ogose, G Tamura, T Chano, Y Kaneko, A Ishikawa, H Orui, T Wada, T Ikeda, M Namba, M Takigawa, H Kawashima, T Hotta, A Tsuchiya, T Ogino, T Motoyama

    CANCER GENETICS AND CYTOGENETICS   158 ( 2 )   148 - 155   2005.4

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    DOI： 10.1016/j.cancergentyto.2004.08.031

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  • Dexamethasone induces apoptosis in proliferative chondrocytes through activation of caspases and suppression of the Akt-phosphatidylinositol 3 '-kinase signaling pathway

    D Chrysis, F Zaman, AS Chagin, M Takigawa, L Savendahl

    ENDOCRINOLOGY   146 ( 3 )   1391 - 1397   2005.3

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    DOI： 10.1210/en.2004-1152

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  • Regulation of chicken ccn2 gene by interaction between RNA cis-element and putative trans-factor during differentiation of chondrocytes

    Y Mukudai, S Kubota, T Eguchi, S Kondo, K Nakao, M Takigawa

    JOURNAL OF BIOLOGICAL CHEMISTRY   280 ( 5 )   3166 - 3177   2005.2

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    DOI： 10.1074/jbc.M411632200

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  • Downregulation of rheumatoid arthritis-related antigen RA-A47 (HSP47/colligin-2) in chondrocytic cell lines induces apoptosis and cell-surface expression of RA-A47 in association with CD9

    T Hattori, K von der Mark, H Kawaki, Y Yutani, S Kubota, T Nakanishi, H Eberspaecher, B de Crombrugghe, M Takigawa

    JOURNAL OF CELLULAR PHYSIOLOGY   202 ( 1 )   191 - 204   2005.1

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    DOI： 10.1002/jcp.20112

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  • Connective tissue growth factor expressed in tubular epithelium plays a pivotal role in renal fibrogenesis

    H Okada, T Kikuta, T Kobayashi, T Inoue, Y Kanno, M Takigawa, T Sugaya, JB Kopp, H Suzuki

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   16 ( 1 )   133 - 143   2005.1

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    DOI： 10.1681/ASN.2004040339

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  • Introduction for CCN proteins.

    Perbal, B, Takigawa, M

    In CCN Proteins: A New Family of Cell Growth and Differentiation Regulators (Perbal B. & Takigawa M. eds.)   1 - 18   2005

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  • Repression of anti-proliferative factor Tob1 in osteoarthritic cartilage

    M Gebauer, J Saas, J Haag, U Dietz, M Takigawa, E Bartnik, T Aigner

    ARTHRITIS RESEARCH & THERAPY   7 ( 2 )   R274 - R284   2005

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    DOI： 10.1186/ar1479

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  • Increased levels of CTGF mRNA expression in a murine model of allergic airway inflammation

    Hong Mei Piao, Kohei Yamauchi, Li-Hua Pan, Toshihide Nakadate, Harumasa Ito, Takashi Mouri, Hitoshi Kobayashi, Takashi Sawai, Tohru Nakanishi, Masaharu Takigawa, Hiroshi Inoue

    Allergology International   54 ( 1 )   107 - 115   2005

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    DOI： 10.2332/allergolint.54.107

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  • CCNファミリー：その構造と機能. Invited

    滝川正春

    細胞   37,462-465   2005

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  • Roles of CCN2/CTGF in the control of growth and regeneration.

    Takigawa, M, Nishida, T, Kubota, S

    In CCN Proteins: A New Family of Cell Growth and Differentiation Regulators (Perbal B. & Takigawa M. eds.)   19 - 59   2005

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  • Cartducin, a Paralog of acrp30/adiponectin, is induced during chondrogenic differentiation and promotes proliferation of chondrogenic precursors and chondrocytes.

    Maeda, T, Jikko, A, Abe, M, Yokohama-Tamaki, T, Akiyama, H, Furukawa, S, Takigawa, M, Wakisaka, S

    J. Cell. Physiol.   206(2),   537 - 544,   2005

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  • Molecular phenotyping of HCS-2/8 cells as an in vitro model of human chondrocytes

    J Saas, K Lindauer, B Bau, M Takigawa, T Aigner

    OSTEOARTHRITIS AND CARTILAGE   12 ( 11 )   924 - 934   2004.11

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    DOI： 10.1016/j.joca.2004.08.002

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  • Implication of prostaglandin E-2 in TNF-alpha-induced release of m-calpain from HCS-2/8 chondrocytes. Inhibition of m-calpain release by NSAIDs

    K Fushimi, S Nakashima, Y Banno, A Akaike, M Takigawa, K Shimizu

    OSTEOARTHRITIS AND CARTILAGE   12 ( 11 )   895 - 903   2004.11

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    DOI： 10.1016/j.joca.2004.08.001

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  • Expression and localization of connective tissue growth factor (CTGF/Hcs24/CCN2) in osteoarthritic cartilage

    S Omoto, K Nishida, Y Yamaai, M Shibahara, T Nishida, T Doi, H Asahara, T Nakanishi, H Inoue, M Takigawa

    OSTEOARTHRITIS AND CARTILAGE   12 ( 10 )   771 - 778   2004.10

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    DOI： 10.1016/j.joca.2004.06.009

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  • Regeneration of defects in the articular cartilage in rat knee joints by connective tissue growth factor hypertrophic chondrocyte-specific gene product 24 CCN family member 2 (CTGF/Hcs24/CCN2).

    T Nishida, S Kubota, T Kuboki, K Nakao, T Kushibiki, Y Tabata, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   19   S216 - S216   2004.10

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  • Connective tissue growth factor causes persistent proa2(I) collagen gene expression induced by transforming growth factor-b in a mouse fibrosis model

    S Chujo, F Shirasaki, T Kinbara, K Takehara, S Kawara, Y Inagaki

    ARTHRITIS AND RHEUMATISM   50 ( 9 )   S624 - S625   2004.9

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  • Differential regulation of biglycan and decorin synthesis by connective tissue growth factor in cultured vascular endothelial cells

    T Kaji, C Yamamoto, M Oh-I, T Nishida, M Takigawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   322 ( 1 )   22 - 28   2004.9

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    DOI： 10.1016/j.bbrc.2004.07.078

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  • Abundant retention and release of connective tissue growth factor (CTGF/CCN2) by platelets

    S Kubota, K Kawata, T Yanagita, H Doi, T Kitoh, M Takigawa

    JOURNAL OF BIOCHEMISTRY   136 ( 3 )   279 - 282   2004.9

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    DOI： 10.1093/jb/mvh126

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  • 低酸素におけるCTGF mRNAの安定化機構 核内タンパク質結合を介した3'-非翻訳領域(UTR)の関与

    近藤 誠二, 久保田 聡, 森谷 徳文, 滝川 正春

    日本癌学会総会記事   63回   400 - 400   2004.9

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  • Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor) Reviewed

    T Nishida, S Kubota, S Kojima, T Kuboki, K Nakao, T Kushibiki, Y Tabata, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   19 ( 8 )   1308 - 1319   2004.8

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    DOI： 10.1359/JBMR.040322

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  • 二次骨化中心形成過程における結合組織成長因子CTGF/CCN2の発現 血管新生因子としての関与

    岡 森彦, 久保田 聡, 江口 傑徳, 河田 かずみ, 黒田 知沙, 皆木 省吾, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   22回   199 - 199   2004.8

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  • ニワトリ軟骨細胞の分化過程におけるCCN2/CTGF遺伝子の転写後発現調節機構の解析

    椋代 義樹, 久保田 聡, 江口 傑徳, 近藤 誠二, 中尾 匡志, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   22回   159 - 159   2004.8

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  • Expression of connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24/CCN2) during distraction osteogenesis

    H Kadota, T Nakanishi, K Asaumi, T Yamaai, E Nakata, S Mitani, K Aoki, A Aiga, H Inoue, M Takigawa

    JOURNAL OF BONE AND MINERAL METABOLISM   22 ( 4 )   293 - 302   2004.7

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    DOI： 10.1007/s00774-004-0486-2

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  • [Cartilage and mechanical stress from the point of the view of development, growth, pathology and therapeutic aspects].

    Takuo Fujisawa, Masaharu Takigawa, Takuo Kuboki

    Clinical calcium   14 ( 7 )   29 - 35   2004.7

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    Articular cartilage is always subjected to various types, magnitudes and cycles of mechanical stress. While it has been recognized that these stresses regulate the chondrocyte growth and differentiation, the mechanism is still unclear. Here, we summarize the effect of mechanical stress on cartilage metabolism from the point of view of development, growth, pathology and therapeutic aspect.

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  • Reduction in connective tissue growth factor by antisense treatment ameliorates renal tubulointerstitial fibrosis

    H Yokoi, M Mukoyama, T Nagae, K Mori, T Suganami, K Sawai, T Yoshioka, M Koshikawa, T Nishida, M Takigawa, A Sugawara, K Nakao

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   15 ( 6 )   1430 - 1440   2004.6

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    DOI： 10.1097/01.ASN.0000130565.69170.85

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  • Gene expression profile of human chondrocyte HCS-2/8 cell line by EST sequencing analysis

    YK Jung, JH Jeong, HM Ryoo, HN Kim, YJ Kim, EK Park, HJ Si, SY Kim, M Takigawa, BH Lee, RW Park, IS Kim, JY Choi

    GENE   330   85 - 92   2004.4

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    DOI： 10.1016/j.gene.2004.01.007

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  • Module-specific antibodies against human connective tissue growth factor: Utility for structural and functional analysis of the factor as related to chondrocytes

    M Minato, S Kubota, H Kawaki, T Nishida, A Miyauchi, H Hanagata, T Nakanishi, T Takano-Yamamoto, M Takigawa

    JOURNAL OF BIOCHEMISTRY   135 ( 3 )   347 - 354   2004.3

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    DOI： 10.1093/jb/mvh042

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  • Connective tissue growth factor(CTGF)の軟骨細胞特異的な転写調節機構の探索

    江口 傑徳, 久保田 聡, 椋代 義樹, 森谷 徳文, 中尾 匡志, 滝川 正春

    生化学   76 ( 3 )   303 - 303   2004.3

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  • 軟骨とメカニカルストレス－発生、成長、病態、治療などとの観点から－。 Invited

    藤澤拓生, 窪木拓男, 滝川正春

    Clinical Calcium   14, 1049-1055 ( 7 )   1049 - 1055   2004

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  • Regulation of chicken ccn2 gene by interaction between RNA cis-element and putative trans-factor during differentiation of chondrocytes.

    Mukudai, Y, Kubota, S, Takanori, E, Kondo, S, Nakao, K, Takigawa, M

    J. Biol. Chem.   280,   3166 - 3177,   2004

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  • Connective tissue growth factor expressed in tubular epithelium plays a pivotal role in renal fibrogenesis.

    Okada H, Kikuta T, Kobayashi T, Inoue T, Kanno Y, Takigawa M, Sugaya T, Kopp JB, Suzuki H

    J. Am. Soc. Nephrol.   16(1),   133 - 143,   2004

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  • Downregulation of rheumatoid arthritis-related antigen RA-A47 (=HSP47/Colligin-2) in chondrocytic cell lines induces apoptosis and cell-surface expression of RA-A47 in association with CD9.

    Hattori, T, von der, Mark, K, Kawaki, H, Yutani, Y, Kubota, S, Nakanishi, T, Eberspeacher, H, de Crombrugghe, B, Takigawa, M

    J. Cell. Physiol.   202,   191 - 204,   2004

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  • CCNファミリー． Invited

    滝川正春

    Molecular Medicine   41, 756-758 ( 6 )   756 - 758   2004

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    Other Link： http://search.jamas.or.jp/link/ui/2004224953

  • Connective tissue growth factor mRNA expression pattern in cartilages is associated with their type I collagen expression

    T Fukunaga, T Yamashiro, S Oya, N Takeshita, M Takigawa, T Takano-Yamamoto

    BONE   33 ( 6 )   911 - 918   2003.12

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    DOI： 10.1016/j.bone.2003.07.010

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  • Downregulation of a rheumatoid arthritis-related antigen (RA-A47) by ra-a47 antisense oligonucleotides induces inflammatory factors in chondrocytes

    T Hattori, H Kawaki, S Kubota, Y Yutani, B De Crombrugghe, K Von Der Mark, M Takigawa

    JOURNAL OF CELLULAR PHYSIOLOGY   197 ( 1 )   94 - 102   2003.10

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    DOI： 10.1002/jcp.10341

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  • Connective tissue growth factor expressed in rat alveolar bone regeneration sites after tooth extraction

    M Kanyama, T Kuboki, K Akiyama, K Nawachi, FM Miyauchi, H Yatani, S Kubota, T Nakanishi, M Takigawa

    ARCHIVES OF ORAL BIOLOGY   48 ( 10 )   723 - 730   2003.10

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    DOI： 10.1016/S0003-9969(03)00153-5

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  • Novel enzyme-linked immunosorbent assay systems for the quantitative analysis of connective tissue growth factor (CTGF/Hcs24/CCN2): Detection of HTLV-I tax-induced CTGF from a human carcinoma cell line

    H Kawaki, S Kubota, M Minato, NH Moritani, T Hattori, H Hanagata, M Kubota, A Miyauchi, T Nakanishi, M Takigawa

    DNA AND CELL BIOLOGY   22 ( 10 )   641 - 648   2003.10

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  • Transcriptional induction of connective tissue growth factor/hypertrophic chondrocyte-specific 24 gene by dexamethasone in human chondrocytic cells Reviewed

    S Kubota, NH Moritani, H Kawaki, H Mimura, M Minato, M Takigawa

    BONE   33 ( 4 )   694 - 702   2003.10

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    DOI： 10.1016/S8756-3282(03)00227-8

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  • CTGFは軟骨においてI型コラーゲンと共発現する

    福永 智広, 山城 隆, 大矢 伸治, 竹下 信郎, 滝川 正春, 山本 照子

    日本矯正歯科学会大会プログラム・抄録集   62回   201 - 201   2003.10

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  • A repetitive, steady mouth opening induced an osteoarthritis-like lesion in the rabbit temporomandibular joint

    T Fujisawa, T Kuboki, T Kasai, W Sonoyama, S Kojima, J Uehara, C Komori, H Yatani, Hattori, I, M Takigawa

    JOURNAL OF DENTAL RESEARCH   82 ( 9 )   731 - 735   2003.9

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  • CTGF/Hcs24/CCN2, hypertrophic chondrocyte-specific gene product, interacts with perlecan in regulating the proliferation and differentiation of chondrocytes.

    T Nishida, S Kubota, T Fukunaga, S Kondo, G Yosimichi, T Nakanishi, T Takano-Yamamoto, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   18   S108 - S108   2003.9

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  • CTGF/Hcs24, hypertrophic chondrocyte-specific gene product, interacts with perlecan in regulating the proliferation and differentiation of chondrocytes Reviewed

    T Nishida, S Kubota, T Fukunaga, S Kondo, G Yosimichi, T Nakanishi, T Takano-Yamamoto, M Takigawa

    JOURNAL OF CELLULAR PHYSIOLOGY   196 ( 2 )   265 - 275   2003.8

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    DOI： 10.1002/jpc.10277

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  • ヒト軟骨肉腫培養細胞株における結合組織成長因子(CTGF)の低酸素による誘導はp38 MAPK経路を介している

    近藤 誠二, 久保田 聡, 森谷 徳文, 滝川 正春

    日本癌学会総会記事   62回   86 - 86   2003.8

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  • Cbfa1/Runx2 gene expression in articular chondrocytes of the mice temporomandibular and knee joints in vivo

    T Kuboki, M Kanyama, T Nakanishi, K Akiyama, K Nawachi, H Yatani, K Yamashita, T Takano-Yamamoto, M Takigawa

    ARCHIVES OF ORAL BIOLOGY   48 ( 7 )   519 - 525   2003.7

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    DOI： 10.1016/S0003-9969(03)00088-8

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  • Transcriptional induction of connective tissue growth factor hypertrophic chondrocyte-specific 24 gene by dexamethasone in human chondrocytic cells

    S Kubota, NH Moritami, H Kawaki, H Mimura, M Minato, M Takigawa

    BONE   32 ( 5 )   S98 - S98   2003.5

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  • Proposal for a unified CCN nomenclature

    DR Brigstock, R Goldschmeding, K Katsube, SCT Lam, LF Lau, K Lyons, C Naus, B Perbal, B Riser, M Takigawa, H Yeger

    JOURNAL OF CLINICAL PATHOLOGY-MOLECULAR PATHOLOGY   56 ( 2 )   127 - 128   2003.4

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  • 顎関節ならびに膝関節の関節軟骨におけるCbfα1/Runx2遺伝子の発現

    窪木 拓男, 完山 学, 中西 徹, 秋山 謙太郎, 縄稚 久美子, 矢谷 博文, 山下 和夫, 山本 照子, 滝川 正春

    日本顎関節学会雑誌   15 ( 1 )   112 - 112   2003.4

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  • Suppressive effect of overexpressed connective tissue growth factor on tumor cell growth in a human oral squamous cell carcinoma-derived cell line

    NH Moritani, S Kubota, T Nishida, H Kawaki, S Kondo, T Sugahara, M Takigawa

    CANCER LETTERS   192 ( 2 )   205 - 214   2003.3

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    DOI： 10.1016/S0304-3835(02)00718-8

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  • Role of CTGF/HCS24/ecogenin in skeletal growth control

    M Takigawa, T Nakanishi, S Kubota, T Nishida

    JOURNAL OF CELLULAR PHYSIOLOGY   194 ( 3 )   256 - 266   2003.3

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  • Conserved repressive regulation of connective tissue growth factor/hypertrophic chondrocyte-specific gene 24 (ctgf/hcs24) enabled by different elements and factors among vertebrate species

    Y Mukudai, S Kubota, M Takigawa

    BIOLOGICAL CHEMISTRY   384 ( 1 )   1 - 9   2003.1

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  • CTGF/Hcs24 as a multifunctional growth factor for fibroblasts, chondrocytes and vascular endothelial cells

    M Takigawa

    DRUG NEWS & PERSPECTIVES   16 ( 1 )   11 - 21   2003.1

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  • 成長因子と軟骨細胞 Invited

    久保田聡, 滝川正春

    腎と骨代謝   16, 103-110   2003

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  • Interaction of AP-1 and the ctgf gene: a possible driver of chondrocyte hypertrophy in growth cartilage

    NH Moritani, S Kubota, T Eguchi, T Fukunaga, T Yamashiro, T Takano-Yamamoto, H Tahara, K Ohyama, T Sugahara, M Takigawa

    JOURNAL OF BONE AND MINERAL METABOLISM   21 ( 4 )   205 - 210   2003

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    DOI： 10.1007/s00774-003-0410-1

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  • Gene expression profiles in chondrosarcoma cells subjected to cyclic stretching and hydrostatic pressure. A cDNA array study

    HM Karjalainen, RK Sironen, MA Elo, K Kaarniranta, M Takigawa, HJ Helminen, MJ Lammi

    BIORHEOLOGY   40 ( 1-3 )   93 - 100   2003

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  • Hepatocyte growth factor counteracts transforming growth factor-beta1, through attenuation of connective tissue growth factor induction, and prevents renal fibrogenesis in 5/6 nephrectomized mice.

    Inoue T, Okada H, Kobayashi T, Watanabe Y, Kanno Y, Kopp J B, Nishida T, Takigawa M, Ueno M, Nakamura T, Suzuki H

    FASEB J   17,   268 - 270,   2003

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  • CTGF/Hcs24 interacts with the cytoskeletal protein actin in chondrocytes

    G Yosimichi, S Kubota, T Hattori, T Nishida, K Nawachi, T Nakanishi, M Kamada, T Takano-Yamamoto, M Takigawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   299 ( 5 )   755 - 761   2002.12

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  • CD44 stimulation by fragmented hyaluronic acid induces upregulation of urokinase-type plasminogen activator and its receptor and subsequently facilitates invasion of human chondrosarcoma cells

    H Kobayashi, M Suzuki, N Kanayama, T Nishida, M Takigawa, T Terao

    INTERNATIONAL JOURNAL OF CANCER   102 ( 4 )   379 - 389   2002.12

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    DOI： 10.1002/ijc.10710

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  • 軟骨細胞におけるチロシンキナーゼ型レセプターErbB4遺伝子の発現

    縄稚 久美子, 久保田 聡, 井上 美穂, 西田 崇, 吉道 玄, 中西 徹, 完山 学, 窪木 拓男, 矢谷 博文, 山合 友一郎, 滝川 正春

    日本骨形態計測学会雑誌   12 ( 3 )   63 - 63   2002.12

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  • 軟骨細胞におけるチロシンキナーゼ型レセプターErbB4遺伝子の発現

    縄稚 久美子, 久保田 聡, 井上 美穂, 西田 崇, 吉道 玄, 中西 徹, 完山 学, 窪木 拓男, 矢谷 博文, 山合 友一郎, 滝川 正春

    生化学   74 ( 11 )   1413 - 1413   2002.11

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  • Expression of connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24) during fracture healing

    E Nakata, T Nakanishi, A Kawai, K Asaumi, T Yamaai, M Asano, T Nishida, S Mitani, H Inoue, M Takigawa

    BONE   31 ( 4 )   441 - 447   2002.10

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  • ラット下顎枝骨折治癒過程の膜性骨化と内軟骨性骨化における結合組織成長因子(CTGF)の経時的発現

    福永 智広, 山城 隆, 小橋 紀之, 滝川 正春, 山本 照子

    日本矯正歯科学会大会プログラム・抄録集   61回   165 - 165   2002.10

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  • Possible roles of CTGF/Hcs24 in the initiation and development of ossification of the posterior longitudinal ligament

    Y Yamamoto, KI Furukawa, K Ueyama, T Nakanishi, M Takigawa, S Harata

    SPINE   27 ( 17 )   1852 - 1857   2002.9

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    DOI： 10.1097/01.BRS.0000025725.06173.C6

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  • Tyrosine kinase-type receptor ErbB4 in chondrocytes: interaction with connective tissue growth factor and distribution in cartilage

    K Nawachi, M Inoue, S Kubota, T Nishida, G Yosimichi, T Nakanishi, M Kanyama, T Kuboki, H Yatani, T Yamaai, M Takigawa

    FEBS LETTERS   528 ( 1-3 )   109 - 113   2002.9

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  • TGF-beta 1 and HGF coordinately facilitate collagen turnover in subepithelial mesenchyme

    T Inoue, H Okada, T Kobayashi, Y Watanabe, T Kikuta, Y Kanno, M Takigawa, H Suzuki

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   297 ( 2 )   255 - 260   2002.9

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  • ヒト口腔扁平上皮癌細胞株における結合組織成長因子(CTGF)の腫瘍細胞増殖抑制効果

    森谷 徳文, 久保田 聡, 近藤 誠二, 西田 崇, 川木 晴美, 菅原 利夫, 滝川 正春

    歯科基礎医学会雑誌   44 ( 5 )   395 - 395   2002.9

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  • Suppression of urokinase receptor expression by bikunin is associated with inhibition of upstream targets of extracellular signal-regulated kinase-dependent cascade

    H Kobayashi, P Suzuki, N Kanayama, T Nishida, M Takigawa, T Terao

    EUROPEAN JOURNAL OF BIOCHEMISTRY   269 ( 16 )   3945 - 3957   2002.8

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    DOI： 10.1046/j.1432-1033.2002.03068.x

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  • CD44 stimulation by fragmented hyaluronic acid induces upregulation and tyrosine phosphorylation of c-Met receptor protein in human chondrosarcoma cells

    M Suzuki, H Kobayashi, N Kanayama, T Nishida, M Takigawa, T Terao

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH   1591 ( 1-3 )   37 - 44   2002.8

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  • cDNA array reveals mechanosensitive genes in chondrocytic cells under hydrostatic pressure

    RK Sironen, HM Karjalainen, MA Elo, K Kaarniranta, K Torronen, M Takigawa, HJ Helminen, MJ Lammi

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH   1591 ( 1-3 )   45 - 54   2002.8

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  • 軟骨由来成長因子CTGF/Hcs24の細胞種特異的遺伝子発現抑制機構の解析

    森谷 徳文, 久保田 聡, 江口 傑徳, 近藤 誠二, 菅原 利夫, 滝川 正春

    生化学   74 ( 8 )   913 - 913   2002.8

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  • 結合組織成長因子CTGF/Hcs24は細胞内で細胞骨格蛋白質と結合する

    吉道 玄, 久保田 聡, 服部 高子, 西田 崇, 縄稚 久美子, 中西 徹, 山本 照子, 滝川 正春

    生化学   74 ( 8 )   797 - 797   2002.8

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  • CTGF/Hcs24, a hypertrophic chondrocyte-specific gene product, stimulates proliferation and differentiation, but not hypertrophy of cultured articular chondrocytes Reviewed

    T Nishida, S Kubota, T Nakanishi, T Kuboki, G Yosimichi, S Kondo, M Takigawa

    JOURNAL OF CELLULAR PHYSIOLOGY   192 ( 1 )   55 - 63   2002.7

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    DOI： 10.1002/jcp.10113

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  • Autoimmunity against YKL-39, a human cartilage derived protein, in patients with osteoarthritis

    JI Tsuruha, K Masuko-Hongo, T Kato, M Sakata, H Nakamura, T Sekine, M Takigawa, K Nishioka

    JOURNAL OF RHEUMATOLOGY   29 ( 7 )   1459 - 1466   2002.7

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  • A novel cis-element that enhances connective tissue growth factor gene expression in chondrocytic cells

    T Eguchi, S Kubota, S Kondo, T Kuboki, H Yatani, M Takigawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   295 ( 2 )   445 - 451   2002.7

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  • 結合組織成長因子(CTGF)の構造・機能解析のためのELISAシステムの開発

    川木 晴美, 久保田 聡, 湊 雅直, 森谷 徳文, 服部 高子, 大山 和美, 中西 徹, 滝川 正春

    岡山歯学会雑誌   21 ( 1 )   182 - 183   2002.6

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  • YKL-39, a human cartilage-related protein, induces arthritis in mice

    M Sakata, K Masuko-Hongo, J Tsuruha, T Sekine, H Nakamura, M Takigawa, K Nishioka, T Kato

    CLINICAL AND EXPERIMENTAL RHEUMATOLOGY   20 ( 3 )   343 - 350   2002.5

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  • Connective tissue growth factor increased by hypoxia may initiate angiogenesis in collaboration with matrix metalloproteinases

    S Kondo, S Kubota, T Shimo, T Nishida, G Yosimichi, T Eguchi, T Sugahara, M Takigawa

    CARCINOGENESIS   23 ( 5 )   769 - 776   2002.5

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  • 軟骨由来軟骨成長因子(CTGF/Hcs24)を用いた関節軟骨再生療法の検討

    小島 俊司, 西田 崇, 小森 千尋, 藤沢 拓生, 窪木 拓男, 矢谷 博文, 中西 徹, 滝川 正春

    日本顎関節学会雑誌   14 ( 1 )   81 - 81   2002.4

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  • ウサギ変形性顎関節症モデルにおける軟骨細胞のアポトーシスの関与

    藤沢 拓生, 笠井 照夫, 窪木 拓男, 矢谷 博文, 服部 高子, 滝川 正春

    日本顎関節学会雑誌   14 ( 1 )   110 - 110   2002.4

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  • Kunitz-type protease inhibitor bikunin disrupts phorbol ester-induced oligomerization of CD44 variant Isoforms containing epitope v9 and subsequently suppresses expression of urokinase-type plasminogen activator in human chondrosarcoma cells

    M Suzuki, H Kobayashi, M Fujie, T Nishida, M Takigawa, N Kanayama, T Terao

    JOURNAL OF BIOLOGICAL CHEMISTRY   277 ( 10 )   8022 - 8032   2002.3

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    DOI： 10.1074/jbc.M108545200

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  • 骨格成長と骨折治癒過程におけるCTGF/Hcs24の遺伝子発現

    滝川 正春, 中西 徹, 西田 崇, 縄稚 久美子, 中田 英二

    厚生労働省特定疾患対策研究事業研究報告書 脊柱靭帯骨化症に関する調査研究班   平成13年度   69 - 76   2002.3

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  • Development of Dentin Regeneration Therapy : Expression of Type I Collagen and Alkaline Phosphatase Induced by CTGF in Human Cultured Dental Pulp

    Hirotoshi SHIMIZU, Yoshihiro NISHITANI, Tomiko YAMADA, Takashi NISHIDA, Masaharu TAKIGAWA, Masahiro YOSHIYAMA, Department of Operative Dentistry Okayama University Graduate School of Medicine and Dentistry, Department of Operative Dentistry Okayama University Graduate School of Medicine and Dentistry, Department of Operative Dentistry Okayama University Graduate School of Medicine and Dentistry, Department of Biochemistry and Molecular Dentistry Okayama University Graduate School of Medicine and Dentistry, Department of Biochemistry and Molecular Dentistry Okayama University Graduate School of Medicine and Dentistry, Department of Operative Dentistry Okayama University Graduate School of Medicine and Dentistry

    Journal of hard tissue biology = Journal of hard tissue biology   11, ( 2 )   62 - 67   2002

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  • High pressure effects on cellular expression profile and mRNA stability. A cDNA array analysis

    RK Sironen, HM Karjalainen, K Torronen, MA Elo, K Kaarniranta, M Takigawa, HJ Helminen, MJ Lammi

    BIORHEOLOGY   39 ( 1-2 )   111 - 117   2002

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  • CTGF/Hcs24, a hypertrophic chondrocyte specific gene product, stimulates the proliferation and expression of the cartilage phenotype but not hypertrophy or calcification or articular cartilage in culture.

    Nishida T, Kubota S, Nakanishi T, Kuboki T, Yosimichi G, Kondo S, Takigawa M

    J Cell Physiol   192,   55 - 63   2002

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  • 岡山大学歯学部におけるチュートリアル教育(2) －5年次生に導入された「Evidence-based medicine(EBM)に基づく歯科医療」の解析と評価－

    宮本 学, 窪木拓男, 高務朋将, 西谷佳浩, 鷲尾憲文, 水口 一, 若狭 享, 多田 徹, 原 哲也, 高木 慎, 福永城司, 真野隆充, 山田庸介, 尾形小霧, 松尾龍二, 永井教之, 矢谷博文, 滝川正春, 山本照子

    岡山歯学会雑誌   21 ( 2 )   247 - 253   2002

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  • Connective tissue growth factor as a major angiogenic agent that is induced by hypoxia in a human breast cancer cell line

    T Shimo, S Kubota, S Kondo, T Nakanishi, A Sasaki, H Mese, T Matsumura, M Takigawa

    CANCER LETTERS   174 ( 1 )   57 - 64   2001.12

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  • CTGF/Hcs24 induces chondrocyte differentiation through a p38 mitogen-activated protein kinase (p38MAPK), and proliferation through a p44/42 MAPK/extracellular-signal regulated kinase (ERK) Reviewed

    G Yosimichi, T Nakanishi, T Nishida, T Hattori, T Takano-Yamamoto, M Takigawa

    EUROPEAN JOURNAL OF BIOCHEMISTRY   268 ( 23 )   6058 - 6065   2001.12

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  • 遺伝子発現の抑圧的調節を仲介するマウスctgf3'-UTR segmentの性質

    近藤 誠二, 久保田 聡, 江口 傑徳, 服部 高子, 中西 徹, 菅原 利夫, 滝川 正春

    日本口腔科学会雑誌   50 ( 6 )   568 - 568   2001.11

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  • Cell-type-specific trans-activation of herpes simplex virus thymidine kinase promoter by the human T-cell leukemia virus type I Tax protein

    S Kubota, Y Mukudai, T Hattori, T Eguchi, S Kondo, M Takigawa

    DNA AND CELL BIOLOGY   20 ( 9 )   563 - 568   2001.9

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  • Novel mode of processing and secretion of connective tissue growth factor/ecogenin (CTGF/Hcs24) in chondrocytic HCS-2/8 cells

    S Kubota, T Eguchi, T Shimo, T Nishida, T Hattori, S Kondo, T Nakanishi, M Takigawa

    BONE   29 ( 2 )   155 - 161   2001.8

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  • 多機能成長因子CTGF/Hcs24遺伝子の転写後制御エレメント,CAESARの作用機序

    久保田 聡, 近藤 誠二, 椋代 義樹, 江口 傑徳, 服部 高子, 中西 徹, 滝川 正春

    生化学   73 ( 8 )   710 - 710   2001.8

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  • Tumor necrosis factor alpha induces expression of genes for matrix degradation in human chondrocyte-like HCS-2/8 cells through activation of NF-kappa B: Abrogation of the tumor necrosis factor alpha effect by proteasome inhibitors

    T Sakai, F Kambe, H Mitsuyama, N Ishiguro, K Kurokouchi, M Takigawa, H Iwata, H Seo

    JOURNAL OF BONE AND MINERAL RESEARCH   16 ( 7 )   1272 - 1280   2001.7

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  • ヒト軟骨肉腫由来軟骨様細胞株HCS-2/8における結合組織成長因子CTGF-Hcs24の遺伝子発現制御機構(Regulatory Mechanism of Human Connective Tissue Growth Factor (CTGF/Hcs24) Gene Expression in a Human Chondrocytic Cell Line, HCS-2/8)

    江口 傑徳, 久保田 聡, 近藤 誠二, 志茂 剛, 服部 高子, 中西 徹, 窪木 拓男, 矢谷 博文, 滝川 正春

    The Journal of Biochemistry   130 ( 1 )   79 - 87   2001.7

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  • In vitro及びin vivoにおける肥大軟骨細胞由来の成長因子CTGF/Hcs24の関節軟骨細胞に対する作用

    西田 崇, 中西 徹, 久保田 聡, 吉道 玄, 近藤 誠二, 滝川 正春

    日本骨代謝学会雑誌   19 ( 2 )   30 - 30   2001.7

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  • CTGF/Hcs24軟骨強制発現トランスジェニックマウスの解析

    縄稚 久美子, 中西 徹, 吉道 玄, 中田 英二, 服部 高子, 小守 壽文, 滝川 正春

    日本骨代謝学会雑誌   19 ( 2 )   30 - 30   2001.7

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  • Type II alveolar epithelial cells and interstitial fibroblasts express connective tissue growth factor in IPF

    LH Pan, K Yamauchi, M Uzuki, T Nakanishi, M Takigawa, H Inoue, T Sawai

    EUROPEAN RESPIRATORY JOURNAL   17 ( 6 )   1220 - 1227   2001.6

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  • Characterization of binding properties of urinary trypsin inhibitor to cell-associated binding sites on human chondrosarcoma cell line HCS-2/8

    Y Hirashima, H Kobayashi, M Suzuki, Y Tanaka, N Kanayama, M Fujie, T Nishida, M Takigawa, T Terao

    JOURNAL OF BIOLOGICAL CHEMISTRY   276 ( 17 )   13650 - 13656   2001.4

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  • Overexpression of connective tissue growth factor hypertrophic chondrocyte-specific gene product 24 decreases bone density in adult mice and induces dwarfism

    T Nakanishi, T Yamaai, M Asano, K Nawachi, M Suzuki, T Sugimoto, M Takigawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   281 ( 3 )   678 - 681   2001.3

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  • Mitogenic effects of neurotrophins on a periodontal ligament cell line Reviewed

    Y Tsuboi, T Nakanishi, T Takano-Yamamoto, M Miyamoto, T Yamashiro, M Takigawa

    JOURNAL OF DENTAL RESEARCH   80 ( 3 )   881 - 886   2001.3

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    DOI： 10.1177/00220345010800030701

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    Other Link： http://orcid.org/0000-0002-4419-9643

  • Change in cellular localization of a rheumatoid arthritis-related antigen (RA-A47) with downregulation upon stimulation by inflammatory cytokines in chondrocytes

    T Hattori, S Kubota, Y Yutani, T Fujisawa, T Nakanishi, K Takahashi, M Takigawa

    JOURNAL OF CELLULAR PHYSIOLOGY   186 ( 2 )   268 - 281   2001.2

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  • Mechanical stimulation induces CTGF expression in rat osteocytes

    T Yamashiro, T Fukunaga, N Kobashi, H Kamioka, T Nakanishi, M Takigawa, T Takano-Yamamoto

    JOURNAL OF DENTAL RESEARCH   80 ( 2 )   461 - 465   2001.2

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  • Expression of transduced HSP70 gene protects chondrocytes from stress

    T Kubo, Y Arai, K Takahashi, T Ikeda, S Ohashi, Kitajima, I, O Mazda, M Takigawa, J Imanishi, Y Hirasawa

    JOURNAL OF RHEUMATOLOGY   28 ( 2 )   330 - 335   2001.2

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  • Recognition of YKL-39, a human cartilage related protein, as a target antigen in patients with rheumatoid arthritis

    T Sekine, K Masuko-Hongo, T Matsui, H Asahara, M Takigawa, K Nishioka, T Kato

    ANNALS OF THE RHEUMATIC DISEASES   60 ( 1 )   49 - 54   2001.1

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  • Cationic polymer-mediated genetic transduction into cultured human chondrosarcoma-derived HCS-2/8 cells

    Suzuyo Ohashi, Toshikazu Kubo, Takumi Ikeda, Yuji Arai, Kenji Takahashi, Yasusuke Hirasawa, Masaharu Takigawa, Etsuko Satoh, Jiro Imanishi, Osam Mazda

    Journal of Orthopaedic Science   6 ( 1 )   75 - 81   2001

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    DOI： 10.1007/s007760170028

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  • 軟骨細胞とMMPs-生理的役割を中心に Invited

    久保田聡, 滝川正春

    The Bone   5, 39-43   2001

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  • Involvement of CTGF, a hypertrophic chondrocyte-specific gene product, in tumor angiogenesis

    T Shimo, T Nakanishi, T Nishida, M Asano, A Sasaki, M Kanyama, T Kuboki, T Matsumura, M Takigawa

    ONCOLOGY   61 ( 4 )   315 - 322   2001

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  • CTGF/Hcs24 induces chondrocyte differentiation through p44/42 MAPK/exracellular-signal regulated kinase (ERK).

    Yosimichi, G, Nakanishi, T, Nishida, T, Hattori, T, Takano-Yamamoto, T, Takigawa, M

    Eur. J. Biochem.   268,   1 - 9,   2001

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  • Cell density-dependent proliferative effects of transforming growth factor (TGF)-beta 1, beta 2, and beta 3 in human chondrosarcoma cells HCS-2/8 are associated with changes in the expression of TGF-beta receptor type I

    K Boumediene, M Takigawa, JP Pujol

    CANCER INVESTIGATION   19 ( 5 )   475 - 486   2001

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  • Mitogenetic effect of neurotrophins on periodonatal ligament cell line.

    Tsuboi, Y, Nakanishi, T, Takano-Yamamoto, T, Miyamoto, M, Yamashiro, T, Takigawa, M

    J. Dent. Res.   80(3),   881 - 886,   2001

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  • Characterization of a mouse ctgf 3 '-UTR segment that mediates repressive regulation of gene expression

    S Kondo, S Kubota, T Eguchi, T Hattori, T Nakanishi, T Sugahara, M Takigawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   278 ( 1 )   119 - 124   2000.11

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  • Expression of connective tissue growth factor in cartilaginous tumors

    T Shakunaga, T Ozaki, N Ohara, K Asaumi, T Doi, K Nishida, A Kawai, T Nakanishi, M Takigawa, H Inoue

    CANCER   89 ( 7 )   1466 - 1473   2000.10

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  • Regulation of human COL2A1 gene expression in chondrocytes - Identification of C-Krox-responsive elements and modulation by phenotype alteration

    C Ghayor, JF Herrouin, C Chadjichristos, L Ala-Kokko, M Takigawa, JP Pujol, P Galera

    JOURNAL OF BIOLOGICAL CHEMISTRY   275 ( 35 )   27421 - 27438   2000.9

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  • Identification of an RNA element that confers post-transcriptional repression of connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) gene: Similarities to retroviral RNA-protein interactions

    S Kubota, S Kondo, T Eguchi, T Hattori, T Nakanishi, RJ Pomerantz, M Takigawa

    ONCOGENE   19 ( 41 )   4773 - 4786   2000.9

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  • Effects of CTGF/Hcs24, a hypertrophic chondrocyte-specific gene product, on the proliferation and differentiation of osteoblastic cells in vitro

    T Nishida, T Nakanishi, M Asano, T Shimo, M Takigawa

    JOURNAL OF CELLULAR PHYSIOLOGY   184 ( 2 )   197 - 206   2000.8

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  • 軟骨由来の成長因子CTGF/Hcs24遺伝子の転写後制御エレメント,CAESARの構造機能連関

    久保田 聡, 近藤 誠二, 江口 傑徳, 服部 高子, 中西 徹, 滝川 正春

    生化学   72 ( 8 )   972 - 972   2000.8

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  • Identity of urinary trypsin inhibitor-binding protein to link protein

    H Kobayashi, Y Hirashima, GW Sun, M Fujie, T Nishida, M Takigawa, T Terao

    JOURNAL OF BIOLOGICAL CHEMISTRY   275 ( 28 )   21185 - 21191   2000.7

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  • Expression of neurotrophins and their receptors (TRK) during fracture healing

    K Asaumi, T Nakanishi, H Asahara, H Inoue, M Takigawa

    BONE   26 ( 6 )   625 - 633   2000.6

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  • 軟骨細胞および線維芽細胞株におけるCTGF/Ecogenin遺伝子発現の3'-UTRによる調節

    近藤 誠二, 久保田 聡, 江口 傑徳, 服部 高子, 中西 徹, 菅原 利夫, 滝川 正春

    岡山歯学会雑誌   19 ( 1 )   205 - 206   2000.6

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  • 軟骨由来の成長因子CTGF/Hcs24遺伝子に同定された新たな転写後制御エレメント,CAESAR

    久保田 聡, 近藤 誠二, 江口 傑徳, 服部 高子, 中西 徹, 滝川 正春

    日本骨代謝学会雑誌   18 ( 2 )   119 - 119   2000.6

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  • Expression of neurotrophins and their receptors (TRK) during fracture healing.

    K Asaumi, T Nakanishi, H Asahara, H Inoue, M Takigawa

    Bone   26 ( 6 )   625 - 633   2000.6

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  • Novel intracellular effects of human connective tissue growth factor expressed in Cos-7 cells

    S Kubota, T Hattori, T Shimo, T Nakanishi, M Takigawa

    FEBS LETTERS   474 ( 1 )   58 - 62   2000.5

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  • Ex vivo gene delivery using an adenovirus vector in treatment for cartilage defects

    T Ikeda, T Kubo, T Nakanishi, Y Arai, K Kobayashi, O Mazda, S Ohashi, K Takahashi, J Imanishi, M Takigawa, Y Hirasawa

    JOURNAL OF RHEUMATOLOGY   27 ( 4 )   990 - 996   2000.4

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  • 軟骨細胞の基質代謝に及ぼす周期的メカニカルストレスの影響

    藤沢 拓生, 服部 高子, 窪木 拓男, 矢谷 博文, 山下 敦, 滝川 正春

    日本顎関節学会雑誌   12 ( 1 )   133 - 134   2000.4

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  • Serum levels of connective tissue growth factor are elevated in patients with systemic sclerosis: Association with extent of skin sclerosis and severity of pulmonary fibrosis

    S Sato, T Nagaoka, M Hasegawa, T Tamatani, T Nakanishi, M Takigawa, K Takehara

    JOURNAL OF RHEUMATOLOGY   27 ( 1 )   149 - 154   2000.1

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  • Effects of CTGF/Hcs24, a product of a hypertrophic chondrocyte-specific gene, on the proliferation and differentiation of chondrocytes in culture

    T Nakanishi, T Nishida, T Shimo, K Kobayashi, T Kubo, T Tamatani, K Tezuka, M Takigawa

    ENDOCRINOLOGY   141 ( 1 )   264 - 273   2000.1

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  • Rheumatoid arthritis-related antigen 47kDa (RA-A47) is a product of colligin-2 and acts as a human HSP47

    T Hattori, K Takahashi, Y Yutani, T Fujisawa, T Nakanishi, M Takigawa

    JOURNAL OF BONE AND MINERAL METABOLISM   18 ( 6 )   328 - 334   2000

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  • Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Synovial Fluids of Patients with Temporomandibular Joint Osteoarthritis

    Manabu Kanyama, Takuo Kuboki, Shunji Kojima, Takuo Fujisawa, Takako Hattori, Masaharu Takigawa, Atsushi Yamashita

    Journal of Orofacial Pain   14 ( 1 )   20 - 30   2000

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  • マトリクラインとMMP Invited

    服部高子, 滝川正春

    現代医療、現代医療社   (4), 909- 915, ( 4 )   909 - 915   2000

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  • Electrophoretic and serologic characterization of 56 kDa antigen (M56) with autologous serum derived from a chondrosarcoma patient: A shared antigen of immunoresponses in cancer and autoimmune diseases

    K Fujiwara, H Udono, T Kunisada, A Kawai, H Inoue, M Takigawa, M Namba, E Nakayama

    ELECTROPHORESIS   20 ( 17 )   3335 - 3342   1999.11

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  • Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: A mouse fibrosis model

    T Mori, S Kawara, M Shinozaki, N Hayashi, T Kakinuma, A Igarashi, M Takigawa, T Nakanishi, K Takehara

    JOURNAL OF CELLULAR PHYSIOLOGY   181 ( 1 )   153 - 159   1999.10

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  • Direct adenovirus-mediated gene delivery to the temporomandibular joint in guinea-pigs

    T Kuboki, T Nakanishi, M Kanyama, W Sonoyama, T Fujisawa, K Kobayashi, T Ikeda, T Kubo, A Yamashita, M Takigawa

    ARCHIVES OF ORAL BIOLOGY   44 ( 9 )   701 - 709   1999.9

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  • Control of delivered gene expression in chondrocytes using heat shock protein 70B promoter

    Y Arai, T Kubo, K Kobayashi, T Ikeda, K Takahashi, M Takigawa, J Imanishi, Y Hirasawa

    JOURNAL OF RHEUMATOLOGY   26 ( 8 )   1769 - 1774   1999.8

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  • 骨・軟骨の発生過程における軟骨由来成長因子CTGF/Hcs24の発現とCbfa1によるその制御

    中西 徹, 浅野 将宏, 縄稚 久美子, 山合 友一郎, 小守 寿文, 西田 崇, 吉道 玄, 久保田 聡, 服部 高子, 滝川 正春

    生化学   71 ( 8 )   1033 - 1033   1999.8

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  • TNFαによるRA-A47の軟骨細胞内局在の変化と抗原提示

    服部 高子, 藤沢 拓生, 油谷 安孝, 中西 徹, 滝川 正春

    生化学   71 ( 8 )   969 - 969   1999.8

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  • Immunohistochemical localization of connective tissue growth factor in the rat central nervous system

    Y Kondo, T Nakanishi, M Takigawa, N Ogawa

    BRAIN RESEARCH   834 ( 1-2 )   146 - 151   1999.7

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  • Connective tissue growth factor induces the proliferation, migration, and tube formation of vascular endothelial cells in vitro, and angiogenesis in vivo

    T Shimo, T Nakanishi, T Nishida, R Asano, M Kanyama, T Kuboki, T Tamatani, K Tezuka, M Takemura, T Matsumura, M Takigawa

    JOURNAL OF BIOCHEMISTRY   126 ( 1 )   137 - 145   1999.7

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  • Physiological function of connective tissue growth factor (CTGF/Hcs24) - Its roles in the process of endochondral ossification Reviewed

    T Nakanishi, M Takigawa

    SEIKAGAKU   71 ( 6 )   429 - 432   1999.6

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  • 骨芽細胞様細胞株MC3T3-E1のメカニカルストレスに対する応答性 神経栄養因子の役割

    稲熊 尚広, 山本 照子, 中西 徹, 山城 隆, 山下 和夫, 滝川 正春

    日本骨代謝学会雑誌   17 ( 2 )   195 - 195   1999.6

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  • アデノウイルスベクター法を用いた顎関節への遺伝子導入の試み

    園山 亘, 中西 徹, 窪木 拓男, 完山 学, 山下 敦, 滝川 正春

    岡山歯学会雑誌   18 ( 1 )   283 - 283   1999.6

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  • Detection of specific antibodies against human cultured chondrosarcoma (HCS-2/8) and osteosarcoma (Saos-2) cells in the serum of patients with osteoarthritis of the temporomandibular joint

    T Kuboki, T Hattori, T Mizushima, M Kanyama, T Fujisawa, A Yamashita, M Takigawa

    ARCHIVES OF ORAL BIOLOGY   44 ( 5 )   403 - 414   1999.5

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  • Cyclic mechanical stress induces extracellular matrix degradation in cultured chondrocytes via gene expression of matrix metalloproteinases and interleukin-1

    T Fujisawa, T Hattori, K Takahashi, T Kuboki, A Yamashita, M Takigawa

    JOURNAL OF BIOCHEMISTRY   125 ( 5 )   966 - 975   1999.5

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  • 周期的な機械的ストレスを培養軟骨細胞に加え続けると,MMP及びIL-1の発現が誘導され,細胞外マトリックスの分解が引き起こされる

    Fujisawa Takuo, Hattori Takako, Takahashi Kojiro, Kuboki Takuo, Yamashita Atsushi, Takigawa Masaharu

    The Journal of Biochemistry   125 ( 5 )   966 - 975   1999.5

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  • Effect of pressure loading on interleukin-8 production in chondrocytes

    Toshikazu Kubo, Yuji Arai, Kenji Takahashi, Toshihiro Ishida, Takuo Fujisawa, Masaharu Takigawa, Jiro Imanishi, Yasusuke Hirasawa

    Pathophysiology   6 ( 1 )   35 - 39   1999.4

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    DOI： 10.1016/S0928-4680(98)00032-7

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  • Involvement of cis-acting repressive element(s) in the 3 '-untranslated region of human connective tissue growth factor gene

    S Kubota, T Hattori, T Nakanishi, M Takigawa

    FEBS LETTERS   450 ( 1-2 )   84 - 88   1999.4

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  • アデノウイルスベクターを用いた顎関節への遺伝子導入の試み

    窪木 拓男, 中西 徹, 完山 学, 園山 亘, 水島 恒尚, 小島 俊司, 山下 敦, 滝川 正春

    日本顎関節学会雑誌   11 ( 1 )   89 - 89   1999.4

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  • Gene delivery to chondrocytes using adenovirus vector Reviewed

    T Kubo, Y Arai, K Kobayashi, J Imanishi, M Takigawa, Y Hirasawa

    ADVANCES IN OSTEOARTHRITIS   107 - 118   1999

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  • 結合組織成長因子CTGF/Hcs24の生理機能 Invited

    中西 徹, 滝川正春

    生化学   71、429-432、 ( 6 )   429 - 432   1999

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    浅海浩二, 中西 徹, 浅原弘嗣, 井上 一, 滝川正春

    骨・関節・靭帯   12、295-297、 ( 3 )   295 - 297   1999

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  • Adenovirus vector-mediated gene transduction to chondrocytes : In vitro evaluation of therapeutic efficacy of transforming growth factor-β1 and heat shock protein 70 gene transduction. Reviewed

    Arai, Y, Kubo, T, Kobayashi, K, Ikeda, T, Takahashi, K, Takigawa, M, Imanishi, J, Hirasawa, Y

    J. Rheumatol.   24   1787 - 1795   1999

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  • Cartilaginous differentiation in the joint capsule

    Y Yutani, Y Yano, H Ohashi, M Takigawa, Y Yamano

    JOURNAL OF BONE AND MINERAL METABOLISM   17 ( 1 )   7 - 10   1999

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  • Expression of osteopontin in Meckel's cartilage cells during phenotypic transdifferentiation in vitro, as detected by in situ hybridization and immunocytochemical analysis Reviewed

    K Ishizeki, S Nomura, M Takigawa, H Shioji, T Nawa

    HISTOCHEMISTRY AND CELL BIOLOGY   110 ( 5 )   457 - 466   1998.11

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  • Increased expression of connective tissue growth factor in the infarct zone of experimentally induced myocardial infarction in rats

    H Ohnishi, T Oka, S Kusachi, T Nakanishi, K Takeda, M Nakahama, M Doi, T Murakami, Y Ninomiya, M Takigawa, T Tsuji

    JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY   30 ( 11 )   2411 - 2422   1998.11

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  • Establishment of the enzyme-linked immunosorbent assay for connective tissue growth factor (CTGF) and its detection in the sera of biliary atresia Reviewed

    T Tamatani, H Kobayashi, K Tezuka, S Sakamoto, K Suzuki, T Nakanishi, M Takigawa, T Miyano

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   251 ( 3 )   748 - 752   1998.10

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  • Adenovirus mediated gene delivery to the joints of guinea pigs Reviewed

    T Ikeda, T Kubo, Y Arai, T Nakanishi, K Kobayashi, K Takahashi, J Imanishi, M Takigawa, Y Hirasawa

    JOURNAL OF RHEUMATOLOGY   25 ( 9 )   1666 - 1673   1998.9

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  • Peripheral type benzodiazepine receptor in T lymphocyte rich preparation Reviewed

    S Maeda, T Miyawaki, T Nakanishi, M Takigawa, M Shimada

    LIFE SCIENCES   63 ( 16 )   1423 - 1430   1998.9

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  • 軟骨細胞の細胞外基質の合成と分解に及ぼす周期的メカニカルストレスの影響

    藤沢 拓生, 服部 高子, 窪木 拓男, 高橋 浩二郎, 山下 敦, 滝川 正春

    歯科基礎医学会雑誌   40 ( 抄録 )   392 - 392   1998.9

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  • 慢性関節リウマチ関連抗原蛋白RA-A47 cDNAの単離と機能解析

    服部 高子, 藤沢 拓生, 中西 徹, 窪木 拓男, 山下 敦, 滝川 正春

    歯科基礎医学会雑誌   40 ( 抄録 )   392 - 392   1998.9

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  • アデノウイルスベクター法を用いた顎関節への遺伝子導入の試み

    完山 学, 中西 徹, 窪木 拓男, 園山 亘, 山下 敦, 滝川 正春

    歯科基礎医学会雑誌   40 ( 抄録 )   450 - 450   1998.9

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  • 慢性関節リウマチ関連抗原蛋白RA-A47 cDNAの単離と構造解析

    服部 高子, 油谷 安孝, 藤沢 拓生, 中西 徹, 高橋 浩二郎, 滝川 正春

    生化学   70 ( 8 )   848 - 848   1998.8

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  • Inhibition of endogenous expression of connective tissue growth factor by its antisense oligonucleotide and antisense RNA suppresses proliferation and migration of vascular endothelial cells Reviewed

    T Shimo, T Nakanishi, Y Kimura, T Nishida, K Ishizeki, T Matsumura, M Takigawa

    JOURNAL OF BIOCHEMISTRY   124 ( 1 )   130 - 140   1998.7

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  • Demonstration of receptors specific for connective tissue growth factor on a human chondrocytic cell line (HCS-2/8) Reviewed

    T Nishida, T Nakanishi, T Shimo, M Asano, T Hattori, T Tamatani, K Tezuka, M Takigawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   247 ( 3 )   905 - 909   1998.6

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  • Stimulatory effects of 4-methylcatechol, dopamine and levodopa on the expression of metallothionein-III (GTF) mRNA in immortalized mouse brain glial cells (VR-2g) Reviewed

    C Aoki, T Nakanishi, N Sogawa, K Ishii, N Ogawa, M Takigawa, H Furuta

    BRAIN RESEARCH   792 ( 2 )   335 - 339   1998.5

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  • Isolation and characterization of a rheumatoid arthritis-specific antigen (RA-A47) from a human chondrocytic cell line (HCS-2/8) Reviewed

    T Hattori, T Fujisawa, K Sasaki, Y Yutani, T Nakanishi, K Takahashi, M Takigawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   245 ( 3 )   679 - 683   1998.4

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  • Hydrostatic pressure induces expression of interleukin 6 and tumour necrosis factor alpha mRNAs in a chondrocyte-like cell line Reviewed

    K Takahashi, T Kubo, Y Arai, Kitajima, I, M Takigawa, J Imanishi, Y Hirasawa

    ANNALS OF THE RHEUMATIC DISEASES   57 ( 4 )   231 - 236   1998.4

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  • Nitric oxide mediates interleukin-1-induced gene expression of matrix metalloproteinases and basic fibroblast growth factor in cultured rabbit articular chondrocytes Reviewed

    K Sasaki, T Hattori, T Fujisawa, K Takahashi, H Inoue, M Takigawa

    JOURNAL OF BIOCHEMISTRY   123 ( 3 )   431 - 439   1998.3

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  • Shikonin, an ingredient of Lithospermum erythrorhizon, inhibits angiogenesis in vivo and in vitro Reviewed

    T Hisa, Y Kimura, K Takada, F Suzuki, M Takigawa

    ANTICANCER RESEARCH   18 ( 2A )   783 - 790   1998.3

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  • Overexpression of c-erbB-3 in various stages of human squamous cell carcinomas Reviewed

    T Funayama, T Nakanishi, K Takahashi, S Taniguchi, M Takigawa, T Matsumura

    ONCOLOGY   55 ( 2 )   161 - 167   1998.3

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  • The inhibition of DNA synthesis by prostaglandin E2 in human gingival fibroblasts is independent of the cyclic AMP-protein kinase A signal transduction pathway. Reviewed International journal

    Arai H, Nomura Y, Kinoshita M, Nishimura F, Takigawa M, Takahashi K, Washio N, Takashiba S, Murayama Y

    Journal of periodontal research   33 ( 1 )   33 - 39   1998.1

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    In this study we attempted to clarify the mechanism of the inhibitory effects of PGE2 on DNA synthesis in Gin-1 (fibroblasts derived from healthy human gingiva) from the aspect of the cyclic AMP-dependent protein kinase signal transduction pathway. PGE2 upregulated intracellular cyclic AMP accumulation and inhibited DNA synthesis in Gin-1 in a dose-dependent manner. When the PGE2-induced intracellular cyclic AMP accumulation was further enhanced by treatment with the cyclic AMP-phosphodiesterase inhibitor, IBMX, the inhibitory effect of PGE2 on DNA synthesis was also enhanced. Furthermore, when we examined the effects of forskolin, an activator of cyclic AMP production, on intracellular cyclic AMP accumulation and DNA synthesis, similar results were obtained. However, inhibitors of cyclic AMP-dependent protein kinase (protein kinase A) such as HA1004 did not diminish the inhibitory effect of PGE2 on DNA synthesis in Gin-1. These results suggest that in Gin-1, PGE2-induced cyclic AMP accumulation may not lead to the activation of protein kinase A or protein kinase A activity may not relate directly to the growth inhibitory effect of PGE2, and that PGE2 does not inhibit DNA synthesis through the cyclic AMP-protein kinase A signal transduction pathway in Gin-1.

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  • Demonstration of receptors for epidermal growth factor on cultured rabbit chondrocytes and regulation of their expression by various growth and differentiation factors. Reviewed

    Nishida,T, Nakanishi,T, Shimo,T, Asano,M, Hattori,T, Tamatani,T, Tezuka,K, Takigawa,M

    Biochem.Biophys.Res.Commun.   183   14 - 20   1998

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  • Insulin-like growth factors I and II are autocrine factors in stimulating proteoglycan synthesis, a marker of differentiated chondrocytes, acting through their respective receptors on a clonal human chondrosarcoma-derived chondrocyte cell line, HCS-2/8 Reviewed

    M Takigawa, T Okawa, HO Pan, C Aoki, K Takahashi, JD Zue, F Suzuki, A Kinoshita

    ENDOCRINOLOGY   138 ( 10 )   4390 - 4400   1997.10

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  • Chondrocytes are regulated by cellular adhesion through CD44 and hyaluronic acid pathway Reviewed

    O Ishida, Y Tanaka, Morimoto, I, M Takigawa, S Eto

    JOURNAL OF BONE AND MINERAL RESEARCH   12 ( 10 )   1657 - 1663   1997.10

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  • Coordinated change between complement C1s production and chondrocyte differentiation in vitro Reviewed

    K Nakagawa, H Sakiyama, T Fukazawa, M Matsumoto, M Takigawa, T Toyoguchi, H Moriya

    CELL AND TISSUE RESEARCH   289 ( 2 )   299 - 305   1997.8

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  • Molecular characterisation of integrin-procollagen C-propeptide interactions Reviewed

    D Davies, DS Tuckwell, DA Calderwood, SA Weston, M Takigawa, MJ Humphries

    EUROPEAN JOURNAL OF BIOCHEMISTRY   246 ( 2 )   274 - 282   1997.6

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  • Cloning of a mRNA preferentially expressed in chondrocytes by differential display PCR from a human chondrocytic cell line that is identical with connective tissue growth factor (CTGF) mRNA Reviewed

    T Nakanishi, Y Kimura, T Tamura, H Ichikawa, Y Yamaai, T Sugimoto, M Takigawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   234 ( 1 )   206 - 210   1997.5

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  • Hydrostatic pressure influences mRNA expression of transforming growth factor-beta 1 and heat shock protein 70 in chondrocyte-like cell line Reviewed

    K Takahashi, T Kubo, K Kobayashi, J Imanishi, M Takigawa, Y Arai, Y Hirasawa

    JOURNAL OF ORTHOPAEDIC RESEARCH   15 ( 1 )   150 - 158   1997.1

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  • The basic effect of IGF on chondrocytes. Reviewed

    Takigawa,M, Kimura,Y, Takahashi,K

    Clin. Pediatr. Endocrinol.   6(suppl10)   169 - 174   1997

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  • A factor in conditioned medium of rabbit costal chondrocytes inhibits the proliferation of cultured entothelial cells and angio-genesis induced by B16 melanoma : its relation with cartilage-derived anti-tumor factor(CATF). Reviewed

    Takigawa, M, Shirai, E, Enomoto, M, Pan, H.-O, Suzuki, F, Shiio, T, Yugari, Y

    Biochem.Int.   14   357 - 364   1997

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  • Nitric oxide mediates interleukin-1-induced matrix degradation and basic fibroblast growth factor release in cultured rabbit articular chondrocytes: A possible mechanism of pathological neovascularization in arthritis Reviewed

    T Tamura, T Nakanishi, Y Kimura, T Hattori, K Sasaki, H Norimatsu, K Takahashi, M Takigawa

    ENDOCRINOLOGY   137 ( 9 )   3729 - 3737   1996.9

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  • Establishment of an in vitro cell derived from human angiosarcoma Reviewed

    T Hisa, S Taniguchi, K Kakudo, M Ichihashi, T Takashima, Y Kato, R Hayakawa, M Takigawa

    BULLETIN DU CANCER   83 ( 7 )   589 - 591   1996.7

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  • Vitamin D inhibits endothelial cell migration Reviewed

    T Hisa, S Taniguchi, D Tsuruta, Y Hirachi, S Ishizuka, M Takigawa

    ARCHIVES OF DERMATOLOGICAL RESEARCH   288 ( 5-6 )   262 - 263   1996.5

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  • Mouse Meckel's cartilage chondrocytes evoke bone-like matrix and further transform into osteocyte-like cells in culture Reviewed

    K Ishizeki, M Takigawa, T Nawa, F Suzuki

    ANATOMICAL RECORD   245 ( 1 )   25 - 35   1996.5

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  • Neurotrophin-3 increases the DNA-binding activities of several transcription factors in a mouse osteoblastic cell line Reviewed

    E Iwata, T Nakanishi, N Ogawa, K Ohyama, T Murakami, M Takigawa

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH   1311 ( 2 )   85 - 92   1996.4

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  • Novel FNR homologues identified in four representative oral facultative anaerobes: Capnocytophaga ochracea, Capnocytophaga sputigena, Haemophilus aphrophilus, and Actinobacillus actinomycetemcomitans Reviewed

    T Hattori, K Takahashi, T Nakanishi, H Ohta, K Fukui, S Taniguchi, M Takigawa

    FEMS MICROBIOLOGY LETTERS   137 ( 2-3 )   213 - 220   1996.4

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  • Expression of c-fos gene inhibits proteoglycan synthesis in transfected chondrocyte Reviewed

    M Tsuji, S Funahashi, M Takigawa, M Seiki, K Fujii, T Yoshida

    FEBS LETTERS   381 ( 3 )   222 - 226   1996.3

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  • Meckel's cartilage chondrocytes in organ culture synthesize bone-type proteins accompanying osteocytic phenotype expression Reviewed

    K Ishizeki, M Takigawa, Y Harada, F Suzuki, T Nawa

    ANATOMY AND EMBRYOLOGY   193 ( 1 )   61 - 71   1996.1

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  • Influence of hydrostatic pressure on expression of heat shock protein 70 and matrix synthesis in chondrocytes Reviewed

    K Takahashi, T Kubo, Y Arai, Y Hirasawa, J Imanishi, K Kobayashi, M Takigawa

    HIGH PRESSURE BIOSCIENCE AND BIOTECHNOLOGY   13   79 - 82   1996

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  • Specific serum antibodies against membranous proteins of a human immortal chondrocytic cell line (HCS-2/8) in rheumatoid arthritis and their relationship to the natural history of this disease Reviewed

    Akira Sakawa, Yasutaka Yutani, Kentaro Inui, Akira Shimazu, Yoshiki Yamano, Akira Kinosita, Fujio Suzuki, Takako Hattori, Masaharu Takigawa

    Journal of Bone and Mineral Metabolism   14 ( 3 )   146 - 152   1996

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    DOI： 10.1007/BF02239482

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  • Interleukin-1 induces Matrix degradation and release of basic fibroblast growth factor in clutured rabbit articular chondrocytes via nitric oxide production : A possible mechanism of pathological neovascularization in arthritis.

    Tamura, T, Makanishi, T, Kimura, Y, Hattori, T, Sasaki, K, Norimatsu, H, Takahashi, K, Takigawa, M, Nitric oxide, mediates interleukin, induced matrix degradation, basic fibroblast growth factor release in cultured rabbit articular chondrocytes, A possible mechanism of, pathological neovascularization in arthritis

    Endocrinology   137 ( 9 )   3729 - 3737   1996

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  • APOPTOSIS IN NORMAL SKIN

    T HISA, S TANIGUCHI, H KOBAYASHI, Y SHIGENAGA, S NOMURA, M TAKIGAWA

    ACTA DERMATO-VENEREOLOGICA   75 ( 5 )   412 - 413   1995.9

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  • PURIFICATION OF AN ANGIOGENESIS INHIBITOR FROM CULTURE-MEDIUM CONDITIONED BY A HUMAN CHONDROSARCOMA-DERIVED CHONDROCYTIC CELL-LINE, HCS-2/8 Reviewed

    Y OHBA, Y GOTO, Y KIMURA, F SUZUKI, T HISA, K TAKAHASHI, M TAKIGAWA

    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS   1245 ( 1 )   1 - 8   1995.8

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  • DEMONSTRATION OF ENDOTHELIN (ET) RECEPTORS ON CULTURED RABBIT CHONDROCYTES AND STIMULATION OF DNA-SYNTHESIS AND CALCIUM INFLUX BY ET-1 VIA ITS RECEPTORS Reviewed

    A KINOSHITA, T TAMURA, C AOKI, T NAKANISHI, S SOBUE, F SUZUKI, K TAKAHASHI, M TAKIGAWA

    CELL BIOLOGY INTERNATIONAL   19 ( 8 )   647 - 654   1995.8

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  • Expression of trkC in a mouse osteoblastic cell line and its response to neurotrophin-3. Reviewed

    Nakanishi T, Ohyama K, Aoki C, Kudo A, Hattori T, Takahashi K, Taniguchi S, Takigawa M

    Biochemical and biophysical research communications   203 ( 2 )   1268 - 1274   1994.9

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  • CHANGES IN PARATHYROID-HORMONE RECEPTORS DURING CHONDROCYTE CYTODIFFERENTIATION Reviewed

    M IWAMOTO, A JIKKO, H MURAKAMI, A SHIMAZU, K NAKASHIMA, M IWAMOTO, M TAKIGAWA, H BABA, F SUZUKI, Y KATO

    JOURNAL OF BIOLOGICAL CHEMISTRY   269 ( 25 )   17245 - 17251   1994.6

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  • PROTOONCOGENE EXPRESSION IN A HUMAN CHONDROSARCOMA CELL-LINE - HCS-2/8 Reviewed

    J ZHU, HO PAN, F SUZUKI, M TAKIGAWA

    JAPANESE JOURNAL OF CANCER RESEARCH   85 ( 4 )   364 - 371   1994.4

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  • CONFORMATION DEPENDENCE OF INTEGRIN-TYPE-II COLLAGEN-BINDING - INABILITY OF COLLAGEN PEPTIDES TO SUPPORT ALPHA(2)BETA(1) BINDING, AND MEDIATION OF ADHESION TO DENATURED COLLAGEN BY A NOVEL ALPHA(5)BETA(1)-FIBRONECTIN BRIDGE Reviewed

    DS TUCKWELL, S AYAD, ME GRANT, M TAKIGAWA, MJ HUMPHRIES

    JOURNAL OF CELL SCIENCE   107   993 - 1005   1994.4

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  • HISTATIN AS A SYNERGISTIC STIMULATOR WITH EPIDERMAL GROWTH-FACTOR OF RABBIT CHONDROCYTE PROLIFERATION Reviewed

    Y MURAKAMI, H NAGATA, S SHIZUKUISHI, K NAKASHIMA, T OKAWA, M TAKIGAWA, A TSUNEMITSU

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   198 ( 1 )   274 - 280   1994.1

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  • DEMONSTRATION OF RECEPTORS FOR EPIDERMAL GROWTH-FACTOR ON CULTURED RABBIT CHONDROCYTES AND REGULATION OF THEIR EXPRESSION BY VARIOUS GROWTH AND DIFFERENTIATION FACTORS Reviewed

    A KINOSHITA, M TAKIGAWA, F SUZUKI

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   183 ( 1 )   14 - 20   1992.2

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  • EFFECTS OF VARIOUS GROWTH AND DIFFERENTIATION FACTORS ON EXPRESSION OF PARATHYROID-HORMONE RECEPTORS ON RABBIT COSTAL CHONDROCYTES IN CULTURE Reviewed

    M TAKIGAWA, A KINOSHITA, M ENOMOTO, A ASADA, F SUZUKI

    ENDOCRINOLOGY   129 ( 2 )   868 - 876   1991.8

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  • ESTABLISHMENT FROM A HUMAN CHONDROSARCOMA OF A NEW IMMORTAL CELL-LINE WITH HIGH TUMORIGENICITY INVIVO, WHICH IS ABLE TO FORM PROTEOGLYCAN-RICH CARTILAGE-LIKE NODULES AND TO RESPOND TO INSULIN INVITRO Reviewed

    M TAKIGAWA, H PAN, A KINOSHITA, K TAJIMA, Y TAKANO

    INTERNATIONAL JOURNAL OF CANCER   48 ( 5 )   717 - 725   1991.7

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  • Establishment from a human chondrosarcoma of a new immortal cell line with abilities to form proteoglycan-rich cartilage nodules and to respond to insulin in vitro and high tumorigenicity in vivo. Reviewed

    Takigawa, M, Pan, H-O, Kinoshita, A, Tajima, K, Takano, Y

    Int. J. Cancer   48   717 - 725   1991

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  • INDUCTION OF ANGIOGENESIS IN CHICK YOLK-SAC MEMBRANE BY POLYAMINES AND ITS INHIBITION BY TISSUE INHIBITORS OF METALLOPROTEINASES (TIMP AND TIMP-2) Reviewed

    M TAKIGAWA, Y NISHIDA, F SUZUKI, J KISHI, K YAMASHITA, T HAYAKAWA

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   171 ( 3 )   1264 - 1271   1990.9

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  • EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON PROLIFERATION AND EXPRESSION OF DIFFERENTIATED PHENOTYPES IN RABBIT COSTAL CHONDROCYTES IN CULTURE Reviewed

    M ENOMOTO, HO PAN, A KINOSHITA, Y YUTANI, F SUZUKI, M TAKIGAWA

    CALCIFIED TISSUE INTERNATIONAL   47 ( 3 )   145 - 151   1990.9

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  • TUMOR ANGIOGENESIS AND POLYAMINES - ALPHA-DIFLUOROMETHYLORNITHINE, AN IRREVERSIBLE INHIBITOR OF ORNITHINE DECARBOXYLASE, INHIBITS B16 MELANOMA-INDUCED ANGIOGENESIS INOVO AND THE PROLIFERATION OF VASCULAR ENDOTHELIAL-CELLS INVITRO Reviewed

    M TAKIGAWA, M ENOMOTO, Y NISHIDA, HO PAN, A KINOSHITA, F SUZUKI

    CANCER RESEARCH   50 ( 13 )   4131 - 4138   1990.7

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  • PHYSIOLOGICAL-ROLE OF VITAMIN-A IN GROWTH CARTILAGE CELLS - LOW CONCENTRATIONS OF RETINOIC ACID STRONGLY PROMOTE THE PROLIFERATION OF RABBIT COSTAL GROWTH CARTILAGE CELLS IN CULTURE Reviewed

    M ENOMOTO, H PAN, F SUZUKI, M TAKIGAWA

    JOURNAL OF BIOCHEMISTRY   107 ( 5 )   743 - 748   1990.5

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  • A CLONAL HUMAN CHONDROSARCOMA CELL-LINE PRODUCES AN ANTI-ANGIOGENIC ANTITUMOR FACTOR Reviewed

    M TAKIGAWA, HO PAN, M ENOMOTO, A KINOSHITA, Y NISHIDA, F SUZUKI, K TAJIMA

    ANTICANCER RESEARCH   10 ( 2A )   311 - 315   1990.3

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  • Insulin-like growth factors (]G0001[) and (]G0002[) are autocrine factors in stimulating proteoglycan synthesis, a marker of differentiated chondrocytes, acting through their respective receptors on a clonal human. chondrosarcoma-derived chondrocyte ce・・・ Reviewed

    Takigawa, M, Kinoshita, A, Enomoto, M, Asada, A, Suzuki, F

    Endocrinology   138   4390 - 4400   1990

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  • POLYAMINES AND ANGIOGENESIS - INHIBITION OF TUMOR ANGIOGENESIS BY THE IRREVERSIBLE INHIBITOR OF ORNITHINE DECARBOXYLASE, ALPHA-DIFLUOROMETHYLORNITHINE Reviewed

    M TAKIGAWA, M ENOMOTO, Y NISHIDA, HO PAN, A KINOSHITA, F SUZUKI

    BIOLOGY AND CHEMISTRY OF POLYAMINES   12   203 - 211   1990

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  • ESTABLISHMENT FROM MOUSE GROWTH CARTILAGE OF CLONAL CELL-LINES WITH RESPONSIVENESS TO PARATHYROID-HORMONE, ALKALINE-PHOSPHATASE ACTIVITY, AND ABILITY TO PRODUCE AN ENDOTHELIAL-CELL GROWTH INHIBITOR Reviewed

    M TAKIGAWA, E SHIRAI, M ENOMOTO, A KINOSHITA, HO PAN, F SUZUKI, Y YUGARI

    CALCIFIED TISSUE INTERNATIONAL   45 ( 5 )   305 - 313   1989.11

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  • DEMONSTRATION OF RECEPTORS FOR PARATHYROID-HORMONE ON CULTURED RABBIT COSTAL CHONDROCYTES Reviewed

    M ENOMOTO, A KINOSHITA, HO PAN, F SUZUKI, YAMAMOTO, I, M TAKIGAWA

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   162 ( 3 )   1222 - 1229   1989.8

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  • ESTABLISHMENT OF A CLONAL HUMAN CHONDROSARCOMA CELL-LINE WITH CARTILAGE PHENOTYPES Reviewed

    M TAKIGAWA, K TAJIMA, HO PAN, M ENOMOTO, A KINOSHITA, F SUZUKI, Y TAKANO, Y MORI

    CANCER RESEARCH   49 ( 14 )   3996 - 4002   1989.7

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  • The distribution of differentiated phenotypes of chondrocytes in osteoarthritic hip. Reviewed

    Yutani, Y, Asada, K, Takigawa, M, Omori, K, Shimazu, A, The distribution of, differentiated phenotypes of chondrocytes in osteoarthritic hip

    Jpn.J.Rheum.Joint Surg.   8   179 - 186   1989

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  • PARATHYROID HORMONE-RESPONSIVE CLONAL CELL-LINES FROM MOUSE GROWTH CARTILAGE Reviewed

    M TAKIGAWA, E SHIRAI, M ENOMOTO, A KINOSHITA, F SUZUKI

    NEW ACTIONS OF PARATHYROID HORMONE   423 - 428   1989

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  • Cartilage-derived anti-tumor factor (CATF) - Partial purification and correlation of inhibitory activity against tumor growth with anti-angiogenic activity Reviewed

    Masaharu Takigawa, Eiji Shirai, Motomi Enomoto, Yuji Hiraki, Fujio Suzuki, Tsuyoshi Shiio, Yasumi Yugari

    Journal of Bone and Mineral Metabolism   6 ( 2 )   29 - 38   1988.8

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    DOI： 10.1007/BF02375643

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  • DIFFERENTIAL-EFFECTS OF 1-ALPHA,25-DIHYDROXYCHOLECALCIFEROL AND 24R,25-DIHYDROXYCHOLECALCIFEROL ON THE PROLIFERATION AND THE DIFFERENTIATED PHENOTYPE OF RABBIT COSTAL CHONDROCYTES IN CULTURE Reviewed

    M TAKIGAWA, M ENOMOTO, E SHIRAI, Y NISHII, F SUZUKI

    ENDOCRINOLOGY   122 ( 3 )   831 - 839   1988.3

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  • HYDROCORTISONE STIMULATION OF PROLIFERATION AND GLYCOSAMINOGLYCAN SYNTHESIS IN RABBIT CRANIOFACIAL CHONDROCYTES INVITRO Reviewed

    M TAKIGAWA, T TAKANO, K NAKAGAWA, M SAKUDA, F SUZUKI

    ARCHIVES OF ORAL BIOLOGY   33 ( 12 )   893 - 899   1988

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  • Enhanced responsiveness to parathyroid hormone and induction of functional differentiation of cultured rabbit costal chondrocytes by a pulsed electromagnetic field

    Yuji Hiraki, Naoto Endo, Masaharu Takigawa, Akira Asada, Hideaki Takahashi, Fujio Suzuki

    BBA - Molecular Cell Research   931 ( 1 )   94 - 100   1987.10

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    DOI： 10.1016/0167-4889(87)90054-1

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  • ENHANCED RESPONSIVENESS TO PARATHYROID-HORMONE AND INDUCTION OF FUNCTIONAL-DIFFERENTIATION OF CULTURED RABBIT COSTAL CHONDROCYTES BY A PULSED ELECTROMAGNETIC-FIELD Reviewed

    Y HIRAKI, N ENDO, M TAKIGAWA, A ASADA, H TAKAHASHI, F SUZUKI

    BIOCHIMICA ET BIOPHYSICA ACTA   931 ( 1 )   94 - 100   1987.10

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  • CHONDROCYTES DEDIFFERENTIATED BY SERIAL MONOLAYER-CULTURE FORM CARTILAGE NODULES IN NUDE-MICE Reviewed

    M TAKIGAWA, E SHIRAI, K FUKUO, K TAJIMA, Y MORI, F SUZUKI

    BONE AND MINERAL   2 ( 6 )   449 - 462   1987.9

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  • A FACTOR IN CONDITIONED MEDIUM OF RABBIT COSTAL CHONDROCYTES INHIBITS THE PROLIFERATION OF CULTURED ENDOTHELIAL-CELLS AND ANGIOGENESIS INDUCED BY B-16 MELANOMA - ITS RELATION WITH CARTILAGE-DERIVED ANTITUMOR FACTOR (CATF) Reviewed

    M TAKIGAWA, E SHIRAI, M ENOMOTO, HO PAN, F SUZUKI, T SHIIO, Y YUGARI

    BIOCHEMISTRY INTERNATIONAL   14 ( 2 )   357 - 363   1987.2

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  • THE EFFECT OF PARATHYROID-HORMONE (1-34) ON CYCLIC-AMP LEVEL, ORNITHINE DECARBOXYLASE ACTIVITY, AND GLYCOSAMINOGLYCAN SYNTHESIS OF CHRONDROCYTES FROM MANDIBULAR CONDYLAR CARTILAGE, NASAL SEPTAL CARTILAGE, AND SPHENO-OCCIPITAL SYNCHONDROSIS IN CULTURE Reviewed

    T TAKANO, M TAKIGAWA, E SHIRAI, K NAKAGAWA, M SAKUDA, F SUZUKI

    JOURNAL OF DENTAL RESEARCH   66 ( 1 )   84 - 87   1987.1

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  • Effects of various tumor promoters on expression of cartilage phenotypes in rabbit costal chondrocytes in culture Reviewed

    Masaharu Takigawa, Koji Tajima, Keisuke Fukuo, Hirota Fujiki, Fujio Suzuki

    Journal of Biochemistry   101 ( 2 )   397 - 404   1987

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    DOI： 10.1093/oxfordjournals.jbchem.a121924

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  • COMPARISON OF INHIBITION BY A TUMOR PROMOTER (12-O-TETRADECANOYLPHORBOL-13-ACETATE) OF EXPRESSION OF THE DIFFERENTIATED PHENOTYPE OF CHONDROCYTES IN RABBIT COSTAL CHONDROCYTES IN CULTURE WITH INHIBITION BY RETINOIC ACID Reviewed

    K FUKUO, M TAKIGAWA, K TAJIMA, M ENOMOTO, Y KUMAHARA, F SUZUKI

    JOURNAL OF BIOCHEMISTRY   99 ( 2 )   385 - 396   1986.2

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  • TUMOR PROMOTER-INDUCED REFRACTORY STATE AGAINST ORNITHINE DECARBOXYLASE INDUCTION BY 12-O-TETRADECANOYLPHORBOL-13-ACETATE IN MOUSE EPIDERMIS Reviewed

    M TAKIGAWA, RC SIMSIMAN, RK BOUTWELL

    CANCER RESEARCH   46 ( 1 )   106 - 112   1986.1

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  • Differential effects of parathyroid hormone and somatomedin-like growth factors on the sizes of proteoglycan monomers and their synthesis in rabbit costal chondrocytes in culture

    Yuji Hiraki, Yasutaka Yutani, Masaharu Takigawa, Yukio Kato, Fujio Suzuki

    BBA - Molecular Cell Research   845 ( 3 )   445 - 453   1985.6

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    DOI： 10.1016/0167-4889(85)90210-1

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  • INDUCTION OF SPERMIDINE SPERMINE N1-ACETYLTRANSFERASE BY PARATHYROID-HORMONE IN RABBIT COSTAL CHONDROCYTES IN CULTURE Reviewed

    MATSUIYUASA, I, S OTANI, S MORISAWA, M TAKIGAWA, M ENOMOTO, F SUZUKI

    JOURNAL OF BIOCHEMISTRY   97 ( 1 )   387 - 390   1985

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  • CARTILAGE-DERIVED ANTI-TUMOR FACTOR (CATF) INHIBITS THE PROLIFERATION OF ENDOTHELIAL-CELLS IN CULTURE Reviewed

    M TAKIGAWA, E SHIRAI, M ENOMOTO, Y HIRAKI, M FUKUYA, F SUZUKI, T SHIIO, Y YUGARI

    CELL BIOLOGY INTERNATIONAL REPORTS   9 ( 7 )   619 - 625   1985

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  • DIFFERENTIAL-EFFECTS OF PARATHYROID-HORMONE AND SOMATOMEDIN-LIKE GROWTH-FACTORS ON THE SIZES OF PROTEOGLYCAN MONOMERS AND THEIR SYNTHESIS IN RABBIT COSTAL CHONDROCYTES IN CULTURE Reviewed

    Y HIRAKI, Y YUTANI, M TAKIGAWA, Y KATO, F SUZUKI

    BIOCHIMICA ET BIOPHYSICA ACTA   845 ( 3 )   445 - 453   1985

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  • STIMULATION BY GLUCOCORTICOIDS OF THE DIFFERENTIATED PHENOTYPE OF CHONDROCYTES AND THE PROLIFERATION OF RABBIT COSTAL CHONDROCYTES IN CULTURE Reviewed

    T TAKANO, M TAKIGAWA, F SUZUKI

    JOURNAL OF BIOCHEMISTRY   97 ( 4 )   1093 - 1100   1985

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  • DIFFERENTIATION AND DE-DIFFERENTIATION OF CULTURED CHONDROCYTES - INCREASE IN MONOMERIC SIZE OF CARTILAGE-SPECIFIC PROTEOGLYCANS BY DIBUTYRYL CYCLIC-AMP AND COMPLETE INHIBITION OF THEIR SYNTHESIS BY RETINOIC ACID Reviewed

    Y HIRAKI, Y YUTANI, M FUKUYA, M TAKIGAWA, F SUZUKI

    BIOCHEMISTRY INTERNATIONAL   10 ( 2 )   267 - 272   1985

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  • EFFECTS OF SYNTHETIC ANALOGS AND FRAGMENTS OF BOVINE PARATHYROID-HORMONE ON ADENOSINE-3',5'-MONOPHOSPHATE LEVEL, ORNITHINE DECARBOXYLASE ACTIVITY, AND GLYCOSAMINOGLYCAN SYNTHESIS IN RABBIT COSTAL CHONDROCYTES IN CULTURE - STRUCTURE-ACTIVITY RELATIONS Reviewed

    T TAKANO, M TAKIGAWA, E SHIRAI, F SUZUKI, M ROSENBLATT

    ENDOCRINOLOGY   116 ( 6 )   2536 - 2542   1985

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  • STUDIES ON CHONDROCYTES FROM MANDIBULAR CONDYLAR CARTILAGE, NASAL SEPTAL CARTILAGE, AND SPHENO-OCCIPITAL SYNCHONDROSIS IN CULTURE .1. MORPHOLOGY, GROWTH, GLYCOSAMINOGLYCAN SYNTHESIS, AND RESPONSIVENESS TO BOVINE PARATHYROID-HORMONE (1-34) Reviewed

    M TAKIGAWA, M OKADA, T TAKANO, H OHMAE, M SAKUDA, F SUZUKI

    JOURNAL OF DENTAL RESEARCH   63 ( 1 )   19 - 22   1984

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  • Cartilage derived anti-tumor factor(CATF) : A high morecular weight in cartilage extract inhibits tumor growth. Reviewed

    Suzuki, F, Takigawa, M, Hiraki, Y, Kato, Y, Fukuo, K. Shiio, T, Yugari, Y

    J.Bone Mineral Metab.   2   231 - 235   1984

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  • CYTOSKELETON AND DIFFERENTIATION - EFFECTS OF CYTOCHALASIN B AND COLCHICINE ON EXPRESSION OF THE DIFFERENTIATED PHENOTYPE OF RABBIT COSTAL CHONDROCYTES IN CULTURE Reviewed

    M TAKIGAWA, T TAKANO, E SHIRAI, F SUZUKI

    CELL DIFFERENTIATION   14 ( 3 )   197 - 204   1984

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  • INHIBITION OF POLYAMINE SYNTHESIS AND PROLIFERATION IN MOUSE L-CELLS BY DL-ALPHA-HYDRAZINO-DELTA-AMINOVALERIC ACID, AN INHIBITOR OF ORNITHINE DECARBOXYLASE Reviewed

    E GOHDA, M TAKIGAWA, H INOUE, Y KATO, Y DAIKUHARA, Y TAKEDA

    JOURNAL OF BIOCHEMISTRY   94 ( 1 )   97 - 106   1983

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  • PURIFICATION OF 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED ORNITHINE DECARBOXYLASE FROM MOUSE EPIDERMIS Reviewed

    FW PERRELLA, M TAKIGAWA, RK BOUTWELL

    INTERNATIONAL JOURNAL OF BIOCHEMISTRY   15 ( 7 )   885 - 889   1983

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  • A bioassay for parathyroid hormone using rabbit costal chondrocytes in culture. Reviewed

    Takano, T, Takigawa, M, Suzuki, F

    Jpn.J.Oral.Biol.   25   394 - 397   1983

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  • RESTORATION BY PARATHYROID-HORMONE AND DIBUTYRYL-CYCLIC-AMP OF EXPRESSION OF THE DIFFERENTIATED PHENOTYPE OF CHONDROCYTES INHIBITED BY A TUMOR PROMOTER, 12-0-TETRADECANOYLPHORBOL-13-ACETATE Reviewed

    M TAKIGAWA, K FUKUO, T TAKANO, F SUZUKI

    CELL DIFFERENTIATION   13 ( 4 )   283 - 291   1983

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  • ROLE OF POLYAMINES IN EXPRESSION OF THE DIFFERENTIATED PHENOTYPE OF CHONDROCYTES - EFFECT OF DL-ALPHA-HYDRAZINO-DELTA-AMINOVALERIC ACID (DL-HAVA), AN INHIBITOR OF ORNITHINE DECARBOXYLASE, ON CHONDROCYTES TREATED WITH PARATHYROID-HORMONE Reviewed

    T TAKANO, M TAKIGAWA, F SUZUKI

    JOURNAL OF BIOCHEMISTRY   93 ( 2 )   591 - 598   1983

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  • THE DIFFERENCE BETWEEN THE EFFECTS OF SINGLE AND DOUBLE APPLICATIONS OF 12-O-TETRADECANOYLPHORBOL-13-ACETATE, A POTENT TUMOR PROMOTER, ON POLYAMINE METABOLISM AND NUCLEIC-ACID SYNTHESIS IN MOUSE EPIDERMIS Reviewed

    M TAKIGAWA, RC SIMSIMAN, RK BOUTWELL

    CARCINOGENESIS   4 ( 1 )   5 - 7   1983

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  • INHIBITION OF MOUSE SKIN TUMOR PROMOTION AND OF PROMOTER-STIMULATED EPIDERMAL POLYAMINE BIOSYNTHESIS BY ALPHA-DIFLUOROMETHYLORNITHINE Reviewed

    M TAKIGAWA, AK VERMA, RC SIMSIMAN, RK BOUTWELL

    CANCER RESEARCH   43 ( 8 )   3732 - 3738   1983

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  • POLYAMINE BIOSYNTHESIS AND SKIN TUMOR PROMOTION - INHIBITION OF 12-O-TETRADECANOYLPHORBOL-13-ACETATE-PROMOTED MOUSE SKIN TUMOR-FORMATION BY THE IRREVERSIBLE INHIBITOR OF ORNITHINE DECARBOXYLASE ALPHA-DIFLUOROMETHYLORNITHINE Reviewed

    M TAKIGAWA, AK VERMA, RC SIMSIMAN, RK BOUTWELL

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   105 ( 3 )   969 - 976   1982

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  • RESTORATION BY CYCLIC-AMP OF THE DIFFERENTIATED PHENOTYPE OF CHONDROCYTES FROM DEDIFFERENTIATED CELLS PRETREATED WITH RETINOIDS Reviewed

    M TAKIGAWA, T TAKANO, F SUZUKI

    MOLECULAR AND CELLULAR BIOCHEMISTRY   42 ( 3 )   145 - 153   1982

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  • SIMULATION OF THE INITIAL-STAGE OF ENDOCHONDRAL OSSIFICATION - INVITRO SEQUENTIAL CULTURE OF GROWTH CARTILAGE CELLS AND BONE-MARROW CELLS Reviewed

    F SUZUKI, T TAKASE, M TAKIGAWA, A UCHIDA, Y SHIMOMURA

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES   78 ( 4 )   2368 - 2372   1981

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  • Effects of parathyroid hormone and cyclic AMP analogues on the activity of ornithine decarboxylase and expression of the differentiated phenotype of chondrocytes in culture Reviewed

    M. Takigawa, T. Takano, F. Suzuki

    Journal of Cellular Physiology   106 ( 2 )   259 - 268   1981

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    DOI： 10.1002/jcp.1041060212

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  • ROLE OF POLYAMINES IN EXPRESSION OF THE DIFFERENTIATED PHENOTYPE OF CHONDROCYTES IN CULTURE Reviewed

    T TAKANO, M TAKIGAWA, F SUZUKI

    MEDICAL BIOLOGY   59 ( 5-6 )   423 - 427   1981

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  • POLYAMINE AND DIFFERENTIATION - INDUCTION OF ORNITHINE DECARBOXYLASE BY PARATHYROID-HORMONE IS A GOOD MARKER OF DIFFERENTIATED CHONDROCYTES Reviewed

    M TAKIGAWA, H ISHIDA, T TAKANO, F SUZUKI

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES   77 ( 3 )   1481 - 1485   1980

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    Language：English   Publishing type：Research paper (scientific journal)  

    Web of Science

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  • Changes in polyamine metabolism of rat liver after administration of D-galactosamine : Favorable effects of putrescine administration on galactosmaine-induced hepatic injury. Reviewed

    Daikuhara, Y, Tamada, F, Takigawa, M, Takeda, Y, Mori, Y

    Gastroenterology   77   123 - 132   1980

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  • Induction by parathyroid hormone of ornithine decarboxylase in rabbit costal chondrocytes in culture. Reviewed

    Takigawa, M, Watanabe, R, Ishida, H, Asada, A, Suzuki, F

    J.Biochem.   85   311 - 314   1979

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  • The role of putrescine in cell proliferation on the skin of mice induced by ethyl-phenylpropiolate. Reviewed

    Takigawa, M, Inoue, H, Gohda, E, Asada, A, Takeda, Y, Mori, Y

    Exp.Mol.Pathol.   27   183 - 196   1977

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  • Effect of DL-α-hydrazino-δ-aninovalerric acid,an inhibitor of ornithine decarboxlase,on polyamine metabolism in isoproterenol-stimulated mouse parotid glands. Reviewed

    Inoue, H, Kato, Y, Takigawa, M, Adachi K, Takeda, Y

    J.Biochem.   77   879 - 893   1975

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  • 軟骨培養細胞株の樹立。 Invited

    滝川正春

    組織培養   15   165 - 169   1900

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Books

  • CCN Proteins: Methods and Protocols, 2nd Edition

    Takigawa M（ Role： Edit）

    Springer-Nature  2023 

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    Total pages：1   Responsible for pages：430   Book type：Scholarly book

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  • CCN Proteins: Methods and Protocols

    Takigawa, M（ Role： Edit）

    2017 

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    Total pages：1   Responsible for pages：576   Book type：Scholarly book

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  • The CCN Proteins: An Overview.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Takigawa M

    Springer  2017 

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    Responsible for pages：1-576.  

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  • CCN proteins in health and disease : an overview of the Fifth International Workshop on the CCN Family of Genes

    Perbal, Annick, 滝川, 正春, Perbal, Bernard V.（ Role： Joint editor）

    Springer  2010.5  （ ISBN:9789048137787 ）

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    Total pages：351   Language：English

    CiNii Books

    ASIN

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  • Role of CCN2/CTGF/Hcs24 in Bone Growth. Int Rev Cytol

    Kubota, S, Takigawa, M

    Academic Press/Elsevier,New York/Amsterdam  2007 

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    Responsible for pages：vol 257, 1-41,  

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  • CTGF(connective tissue growth factor). Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Kubota, S, Takigawa, M

    2007 

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  • UCSD/Nature The Signaling Gateway

    Kubota, S, Takigawa, M

    2007 

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  • CCN proteins : a new family of cell growth and differentiation regulators International journal

    Perbal, Bernard, Takigawa, Masaharu（ Role： Edit）

    Imperial College Press  2005  （ ISBN:186094552X ）

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    Total pages：xi, 311 p.   Language：English Book type：Scholarly book

    CiNii Books

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  • The CCN proteins - The CCN family of proteins: an overview.

    （ Role： Contributor）

    In CCN Proteins: A New Family of Cell Growth and Differentiation Regulators  2005 

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  • CCN Proteins: A New Family of Cell Growth and Differentiation Regulators

    Perbal, B, Takigawa, M（ Role： Edit）

    Imperial College Press  2005 

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    Responsible for pages：pp. 1-311  

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  • The role of polyamines in restoration of the differentiated phenotype of chondrocytes from de-differentiated cells pretreated with retinoic acid and a tumor promoter.

    Polyamines : Basic and Clinical Aspects(eds.K.Imahori,F.Suzuki,O.Suzuki,& U.Bachrach)VNU Science Press 

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  • CCN in Encyclopedia of Signaling Molecules (Choi E ed),. 2nd edition

    Kubota, S, Takigawa, M（ Role： Contributor）

    Springer  2018 

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    Responsible for pages：814-827  

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  • Preparation of Module-Specific Antibodies Against CCN Family Members.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Analysis of Transcytosis of CCN2 by Chondrocytes.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Analysis of Pathological Activities of CCN Proteins in Bone Metastasis.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Protocols for Screening Peptide Motifs Binding to CCN Family Proteins.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Protocols for Screening for Binding Partners of CCN Proteins: Yeast Two-Hybrid System.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Promoter Analyses of CCN Genes.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Evaluation of Molecular Interaction between CCN2 Protein and Its Binding Partners by Surface Plasmon Resonance (SPR).in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Protein Imaging of CCN2 and CCN3 in Living Cells.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Analysis of Posttranscriptional Regulation of CCN Genes.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Cell Biological Assays for Measuring Angiogenic Activities of CCN Proteins.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Cell Biological Assays for Measuring Chondrogenic Activities of CCN2 Protein.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Generation and Analysis of Cartilage-Specific CCN2 Overexpression in Transgenic Mice.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • In Vivo Evaluation of Cartilage Regenerative Effects of CCN2 Protein. in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Gene Expression Analysis of CCN Proteins: Whole-Mount In Situ Hybridization of Ccn2 in Developing Calcified Tissues.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Analysis of Signaling Pathways Activated by CCN Proteins.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Western blotting analysis of CCN proteins in Calcified Tissues.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Analysis of Expression of CCN Family Genes in Skeletal Tissue-Derived Cells.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Production of Recombinant CCN2 Protein in Escherichia coli.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Immunohistochemical Analysis of CCN Proteins in Calcified Tissues.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • In Vitro Transfection with and Expression of CCN Family of Genes.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • Production of Recombinant CCN2 Protein by Mammalian Cells.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • ELISA of CCN Family Proteins in Body Fluids Including Serum and Plasma.in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Springer  2017 

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  • CCN proteins in health and disease : an overview of the Fifth International Workshop on the CCN Family of Genes

    Perbal, Annick, 滝川, 正春, Perbal, Bernard.（ Role： Joint editor）

    Springer  2010.5  （ ISBN:9789048137787 ）

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    Total pages：351   Language：English

    CiNii Books

    ASIN

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  • Novel transcriptional regulation of CCN2/CTGF by nuclear translocation of MMP3. In CCN Proteins in Health and Disease MMP3

    Springer  2010 

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  • Nucleophosmin/B23: A multifunctional regulator that determines the fate of ccn2 mRNA. In CCN Proteins in Health and Disease

    Springer  2010 

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  • Cooperative regulation of cell proliferation and differentiation by CCN2 and CCN3. In CCN Proteins in Health and Disease

    Springer  2010 

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  • CCN Proteins in Health and Disease

    Perbal, A, Takigawa, M, Perbal, B

    2010 

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    Total pages：1-388  

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  • 細胞増殖因子と再生医療

    メディカルレビュー社 ,大阪  2006 

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  • 軟骨修復－CCN2/CTGF 細胞増殖因子と再生医療

    メディカルレビュー社  2006 

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  • Roles of CCN2/CTGF in the control of growth and regeneration. in CCN Proteins : A New Family of Cell Growth and Differentiation Regulators

    Takigawa M, Nishida T, Kubota S

    2005 

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  • The CCN Family Proteins :An Overview in CCN Proteins : A new family of cell growth and differentiation regulators

    Perbal, Bernard V., 滝川, 正春（ Role： Edit）

    Imperial College Press  2005  （ ISBN:186094552X ）

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    Total pages：xi, 311 p.   Language：English

    CiNii Books

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  • Recent Research Development in Biphysics and Biochemistry

    Research Signpost,Kerara  2003 

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  • 遺伝子医学別冊「ドラッグデリバリーシステム、DDS技術の新たな展開とその活用法」.

    メディカルドｳ社,東京  2003 

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  • 骨軟骨の生物学

    金原出版,東京  2002 

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  • 中富健康科学振興財団研究助成業績集

    2002 

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  • 第４回生体組織工学シンポジウム資料集

    2002 

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  • 骨・軟骨のバイオロジー－基礎から臨 床への展開

    金原出版  2001 

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  • 新・分子骨代謝学と骨粗鬆症

    メディカルレビュー社  2001 

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  • 骨・軟骨のバイオロジー－基礎から臨床への展開

    金原出版  2001 

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  • 第３回生体組織工学シンポジウム資料集

    2001 

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  • 第２回生体組織工学シンポジウム

    2000 

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  • In Tissue Engineering for Therapeutic Use 4.(ed, Shimizu, Y.).

    Elsevier  2000 

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  • 第１４回未来開拓事業学術推進事業「再生医工学」研究推進委員会資料

    1999 

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  • Cytochemical and biochemical approches to masticatory system.

    Mechanobiological Research on the Masticatory System(ed.K.Kubota)VEB Verlage fur Medizin und Biologie 

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  • 6.軟骨、6.1.軟骨細胞-細胞培養を中心に最新組織培養応用研究法

    lnvitroアッセイ有用物質生産(山根績編)ソフトサイエンス社 

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  • Physiological roles of connective tissue growth factor(CTGF/Hcs24) : promotion of endochondral ossification, angiogenesis and tissue remodeling.

    In Tissue Engineering for Therapeutic Use 

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  • Observations on the mechanism of skin tumor promotion by phorbol esters.

    Cellular Inter-actions by Environmental Tumor Promoter,Edited by H.Fugiki,E Heker.R.E.Moor,T.Sugimura and I.B.Weinstein,Japan Sci.Soc.Press VNU Science Press 

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  • Evidence that an elevated level of ornithine decarboxylase may be essential to tumor promotion by phorbol esters.

    Polyamines : Basic and Clinical Aspects(eds.K.Imahori,F.Suzuki,O.Suzuki,& U.Bachrach)VNU Science Press 

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  • The CCN proteins - The CCN family of proteins: an overview.

    In CCN Proteins: A New Family of Cell Growth and Differentiation Regulators 

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  • The role of polyamines in restoration of the differentiated phenotype of chondrocytes from de-differentiated cells pretreated with retinoic acid and a tumor promoter.

    Polyamines : Basic and Clinical Aspects(eds.K.Imahori,F.Suzuki,O.Suzuki,& U.Bachrach)VNU Science Press 

    　More details

  • Induction of ornithine decarboxylase and spermidine/spermine N1-acetyltransferase by parathyroid hormone in rabbit costal chondrocytes in culture.

    Polyamines : Basic and Clinical Aspects(eds.K.Imahori,F.Suzuki,O.Suzuki,& U.Bachrach)VNU Science Press 

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  • Sensitization of rabbit costal chondrocytes to parathyroid hormone by pulsing electro-magnetic field stimulation.

    Bioelectrical Repair and Growth(eds.E.Fukuda,S.Inoue,T.Sakou,H.Takahashi & N.Tsuyama)Nishimura Shoten 

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  • Retionoids as inhibitors of tumor promotion.

    Retinoids : New Trends in Research and Therapy(ed.J.H.Saurat)Kargel 

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  • Polyamines and angiogenesis : Inhibition of tumor angiogenesis by the irreversible inhibitor of ornithine decarboxylase,α-difluoromethyl-ornithine.

    Proccedings of 1989 International Symposium on The Biology and Chemistry of Polyamines(eds.I.D.Algranati & T.Oshima)ICSU Press 

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  • 血管新生に関与する因子とその作用機序;化学的因子;ポリアミン。

    血管新生治療-基礎と臨床-(内田康美、小塚裕編)真興交易医書出版社 

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  • Physiological roles of connective tissue growth factor(CTGF/Hcs24) : promotion of endochondral ossification, angiogenesis and tissue remodeling.

    In Tissue Engineering for Therapeutic Use 

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  • Evidence that an elevated level of ornithine decarboxylase may be essential to tumor promotion by phorbol esters.

    Polyamines : Basic and Clinical Aspects(eds.K.Imahori,F.Suzuki,O.Suzuki,& U.Bachrach)VNU Science Press 

    　More details

  • Induction of ornithine decarboxylase and spermidine/spermine N1-acetyltransferase by parathyroid hormone in rabbit costal chondrocytes in culture.

    Polyamines : Basic and Clinical Aspects(eds.K.Imahori,F.Suzuki,O.Suzuki,& U.Bachrach)VNU Science Press 

    　More details

  • Sensitization of rabbit costal chondrocytes to parathyroid hormone by pulsing electro-magnetic field stimulation.

    Bioelectrical Repair and Growth(eds.E.Fukuda,S.Inoue,T.Sakou,H.Takahashi & N.Tsuyama)Nishimura Shoten 

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  • Retionoids as inhibitors of tumor promotion.

    Retinoids : New Trends in Research and Therapy(ed.J.H.Saurat)Kargel 

    　More details

  • Polyamines and angiogenesis : Inhibition of tumor angiogenesis by the irreversible inhibitor of ornithine decarboxylase,α-difluoromethyl-ornithine.

    Proccedings of 1989 International Symposium on The Biology and Chemistry of Polyamines(eds.I.D.Algranati & T.Oshima)ICSU Press 

    　More details

  • Cytochemical and biochemical approches to masticatory system.

    Mechanobiological Research on the Masticatory System(ed.K.Kubota)VEB Verlage fur Medizin und Biologie 

    　More details

  • Parathyroid hormone-responsive clonal cell lines from mouse growth cartilage.

    New Action of Parathyroid Hormone(ed.Massry,S.G.)Plenum Publishing Corp. 

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  • Observations on the mechanism of skin tumor promotion by phorbol esters.

    Cellular Inter-actions by Environmental Tumor Promoter,Edited by H.Fugiki,E Heker.R.E.Moor,T.Sugimura and I.B.Weinstein,Japan Sci.Soc.Press VNU Science Press 

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  • 軟骨由来血管内皮細胞増殖阻害因子の探索。

    がんに対する生体防御機構-日免疫系抗腫瘍因子を中心として(今西二郎編)共和書院 

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  • MGC/T1.17.

    動物培養細胞胞マニュアル(瀬野悍二、小山英機、黒木登志夫編)共立出版 

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  • 軟骨細胞の分化。

    Bone science講座[(]G0002[)]骨形成と吸収、及びそれらの調節因子(須田立雄編)広川書店 

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  • HCS.2/8.

    動物培養細胞胞マニュアル(瀬野悍二、小山英機、黒木登志夫編)共立出版 

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  • CTGF/Hcs24・CCN2 as a regeneration factor(regenerin) acting on various types of mesemchymal cells.

    In Trend in Stem Cell Research ,(Columbus F. ed),Nova Science(New York), 

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  • Physiological roles of connective tissue growth factor(CTGF/Hcs24)

    promotion of endochondral ossification,angiogenesis and tissue remodeling,In Tissue Engineering for Therapeutic Use(ed,Shimizu,Y.).Vol.4.,Elsevier,Amsterdam 

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  • 血管内皮細胞増殖制御因子。

    血管細胞の培養法とその応用。室田誠逸編、東京化学同人 

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  • 軟骨由来抗腫瘍因子。

    新しいサイトカイン-非免疫系抗腫瘍因子(今西二郎編)金芳堂 

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  • Receptor. 組織別レセプター論-各種レセプターの相互関連を中心に-18. 軟骨細胞。

    日本臨床 

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  • Parathyroid hormone-responsive clonal cell lines from mouse growth cartilage.

    New Action of Parathyroid Hormone(ed.Massry,S.G.)Plenum Publishing Corp. 

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  • 軟骨内骨化の分子制御

    分子骨代謝学と骨粗しょう症、(松本俊夫編)、メディカルレビュー社 

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  • 1.代謝と栄養、3.臓器の代謝と機能、3.6.2.硬組織

    生化学 データブックII、日本生化学会編、東京化学同人 

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MISC

  • Terminology of CCN1-6 should not be applicable for their fragments and be limited to only full length CCN1-6 Reviewed

    Masaharu Takigawa

    J Cell Commun Signal   9 ( 1 )   81 - 83   2015.3

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    Authorship：Lead author,　Last author,　Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    DOI： 10.1007/s12079-015-0269-7

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  • CCN family genes in the development and differentiation of cartilage tissues

    Satoshi Kubota, Masaharu Takigawa

    Clinical calcium   16 ( 3 )   486 - 492   2006

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    Language：Japanese   Publishing type：Book review, literature introduction, etc.  

    Scopus

    PubMed

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  • 軟骨組織においてCCN3は加齢に伴って発現上昇するが,その発現上昇は,年齢,荷重の有無に関わらず軟骨変性度と相関する

    服部高子, 桑原実穂, 廣瀬一樹, 近藤星, FU Shanqi, 滝川正春, 久保田聡

    日本骨代謝学会学術集会プログラム抄録集(CD-ROM)   42nd   2024

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  • 軟骨組織の加齢とともに発現が上昇するCCN3は、その発現上昇と軟骨変性度が年齢、荷重の有無に関わらず相関する

    桑原 実穂, 廣瀬 一樹, 近藤 星, Fu Shanqi, 大野 充昭, 古松 毅之, 中田 英二, 滝川 正春, 久保田 聡, 服部 高子

    日本生化学会大会プログラム・講演要旨集   96回   [2P - 516]   2023.10

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    Language：Japanese   Publisher：(公社)日本生化学会  

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  • CCN3は軟骨細胞老化マーカーであり、年齢、荷重の有無に関わらず変形性関節症と相関する

    服部 高子, 滝川 正春, 久保田 聡, 桑原 実穂, 廣瀬 一樹

    Journal of Oral Biosciences Supplement   2023   [O3 - 03]   2023.9

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    Language：Japanese   Publisher：(一社)歯科基礎医学会  

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  • CCN3は軟骨細胞老化マーカーであり,年齢,荷重の有無に関わらず変形性関節症と相関する

    服部高子, 滝川正春, 久保田聡

    Journal of Oral Biosciences Supplement (Web)   2023   2023

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  • Intraflagellar transport protein88によるHippo経路と古典的WNT経路を介した象牙芽前駆細胞増殖制御の可能性

    河田かずみ, 青山絵理子, 滝川正春, 久保田聡

    Journal of Oral Biosciences Supplement (Web)   2023   2023

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  • S-adenosylmethionine promotes chondrocyte differentiation via polyamine synthesis and gene expression of growth factors.

    LOC Hoangdinh, LOC Hoangdinh, 青山絵理子, 日浅未来, 表弘志, 久保田聡, 窪木拓男, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   35th   2023

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  • The effects of binding of CCN2 to GDF5 and its receptors on chondrocytes

    東原直裕, 東原直裕, 東原直裕, 青山絵理子, 古松毅之, 久保田聡, 尾崎敏文, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   35th   2023

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  • GDF5およびその受容体との結合を介したCCN2の軟骨細胞分化制御機構

    東原直裕, 東原直裕, 青山絵理子, 古松毅之, 久保田聡, 尾崎敏文, 滝川正春

    日本整形外科学会雑誌   97 ( 8 )   2023

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  • CCN3, a senescence marker of cartilage, correlate with osteoarthritis irrespective of age and weight bearing

    桑原実穂, 廣瀬一樹, 廣瀬一樹, 奥田龍一郎, HABUMUGISHA Janvier, 近藤星, FU Shanqi, 大野充昭, 古松毅之, 中田英二, 滝川正春, 久保田聡, 服部高子

    日本分子生物学会年会プログラム・要旨集(Web)   46th   2023

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  • 軟骨組織の加齢変性におけるCCN3の機能

    桑原 実穂, 近藤 星, Fu Shanqi, 大野 充昭, 古松 毅之, 中田 英二, 滝川 正春, 服部 高子, 久保田 聡

    日本生化学会大会プログラム・講演要旨集   95回   1T14a - 08   2022.11

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    Language：Japanese   Publisher：(公社)日本生化学会  

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  • S-アデノシルメチオニンはポリアミン産生だけでなく増殖因子の遺伝子発現を促進することによって軟骨分化を促進する(S-adenosylmethionine induces chondrocytic differentiation not only as source of polyamine production but also by stimulating growth factor genes expression)

    ホアンディン・ロック, 青山 絵理子, 久保田 聡, 窪木 拓男, 滝川 正春

    Journal of Oral Biosciences Supplement   2022   134 - 134   2022.9

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    Language：English   Publisher：(一社)歯科基礎医学会  

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  • 高転移性癌細胞由来の細胞外小胞に搭載されたMMP3によるCtgf/Ccn2発現調節機能と癌転移促進(Extracellular vesicles enriched with moonlighting metalloproteinase are highly transmissive, Pro-tumorigenic, and trans-activates cellular communication network factor(CCN2/CTGF): CRISPR against cancer)

    奥舎 有加, 江口 傑徳, Tran Manh T., 十川 千春, 吉田 賀弥, 板垣 まみ, Taha Eman A., 小野 喜章, 青山 絵理子, 岡村 裕彦, 小崎 健一, Calderwood Stuart K., 滝川 正春, 岡元 邦彰

    Journal of Oral Biosciences Supplement   2022   35 - 35   2022.9

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  • 変形性肩関節症とCCN3発現上昇との相関について

    廣瀬 一樹, 中田 英二, 服部 高子, 鉄永 智紀, 山田 和希, 佐藤 嘉洋, 桑原 実穂, 滝川 正春, 久保田 聡, 尾崎 敏文

    移植   56 ( 4 )   455 - 455   2022.2

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  • 変形性股関節症とCCN3発現の相関

    廣瀬一樹, 廣瀬一樹, 服部高子, 桑原実穂, 滝川正春, 中田英二, 鉄永智紀, 山田和希, 佐藤嘉洋, 小浦卓, 尾崎敏文, 久保田聡

    日本骨代謝学会学術集会プログラム抄録集(CD-ROM)   40th   2022

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  • 変形性股関節症とCCN3の相関

    廣瀬一樹, 廣瀬一樹, 中田英二, 鉄永智紀, 山田和希, 小浦卓, 井上智博, 服部高子, 滝川正春, 久保田聡, 尾崎敏文

    日本股関節学会学術集会プログラム・抄録集   49th   2022

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  • Metformin regulates expression of long non-coding RNA, UCA1 and CCN2 in chondrocytes

    近藤星, 近藤星, 服部高子, 桑原実穂, FU Shanqi, 西田崇, 薬師寺翔太, 吉岡洋祐, 森谷徳文, 森谷徳文, 飯田征二, 滝川正春, 久保田聡

    日本分子生物学会年会プログラム・要旨集(Web)   45th   2022

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  • 変形性股関節症とCCN3発現の相関

    廣瀬一樹, 服部高子, 滝川正春, 中田英二, 鉄永智紀, 山田和希, 佐藤嘉洋, 小浦卓, 尾崎敏文, 久保田聡

    日本骨形態計測学会雑誌   32 ( 1 )   2022

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  • C型レクチン受容体CD302による骨芽細胞の接着制御機構の解明

    青山絵理子, 久保田聡, 滝川正春

    日本生化学会大会(Web)   95th   2022

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  • Physiological significance of binding of GDF5 and CCN2 on chondrocytes

    東原直裕, 東原直裕, 青山絵理子, 古松毅之, 久保田聡, 尾崎敏文, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   34th   2022

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  • C-type lectin receptor CD302 positively regulates the migration and adhesion of osteoblasts

    青山絵理子, 久保田聡, 滝川正春

    日本分子生物学会年会プログラム・要旨集(Web)   45th   2022

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  • フッ化ナトリウムによるCCNファミリー遺伝子制御を介した歯肉線維化抑制作用の検討

    水川 朋美, 西田 崇, 明石 翔, 大杉 綾花, 大森 一弘, 中山 真彰, 高柴 正悟, 上岡 寛, 滝川 正春, 久保田 聡

    岡山歯学会雑誌   40 ( 2 )   34 - 35   2021.12

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  • メトホルミンによるUCA1を介した軟骨保護作用の解析

    近藤 星, 服部 高子, 桑原 実穂, Fu Shanqi, 西田 崇, 薬師寺 翔太, 吉岡 洋祐, 森谷 徳文, 飯田 征二, 滝川 正春, 久保田 聡

    岡山歯学会雑誌   40 ( 2 )   38 - 39   2021.12

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  • 軟骨細胞におけるRFX1を介したCCN3の発現制御機構の解明

    水川 朋美, 西田 崇, 明石 翔, 河田 かずみ, 菊池 菫, 川木 晴美, 滝川 正春, 上岡 寛, 久保田 聡

    日本生化学会大会プログラム・講演要旨集   94回   [2T15a - 638)]   2021.11

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  • CCN6は口腔がん細胞の上皮間葉転換と破骨細胞形成を抑制する(CCN6 suppresses epithelial-mesenchymal transition of oral cancercells and osteoclast formation)

    芳地 浩彰, 西田 崇, 滝川 正春, 久保田 聡

    Journal of Oral Biosciences Supplement   2021   250 - 250   2021.10

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  • S-アデノシルメチオニンによる軟骨細胞分化促進作用とそのメカニズムの解析

    ほあん・ろっく, 青山 絵理子, 久保田 聡, 窪木 拓男, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   39回   139 - 139   2021.10

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  • OCN3は関節軟骨の加齢性変性を促進する

    桑原 実穂, 近藤 星, Fu Shanqi, 大野 充昭, 古松 毅之, 中田 英二, 滝川 正春, 久保田 聡, 服部 高子

    日本骨代謝学会学術集会プログラム抄録集   39回   138 - 138   2021.10

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  • 変形性肩関節症モデルとしてのCCN3過剰発現マウス

    廣瀬 一樹, 服部 高子, 中田 英二, 鉄永 智紀, 山田 和希, 佐藤 嘉洋, 桑原 実穂, 尾崎 敏文, 滝川 正春, 久保田 聡

    日本骨代謝学会学術集会プログラム抄録集   39回   151 - 151   2021.10

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  • 飢餓状態の軟骨細胞におけるRFX1を介したCCN3の誘導機構とその意義

    水川 朋美, 西田 崇, 河田 かずみ, 川木 晴美, 滝川 正春, 久保田 聡

    日本骨代謝学会学術集会プログラム抄録集   39回   144 - 144   2021.10

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  • S-アデノシルメチオニンによる軟骨細胞分化促進作用とそのメカニズムの解析

    ほあん・ろっく, 青山 絵理子, 久保田 聡, 窪木 拓男, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   39回   139 - 139   2021.10

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  • 変形性肩関節症とCCN3発現上昇との相関について

    廣瀬 一樹, 中田 英二, 服部 高子, 鉄永 智紀, 山田 和希, 佐藤 嘉洋, 桑原 実穂, 滝川 正春, 久保田 聡, 尾崎 敏文

    日本整形外科学会雑誌   95 ( 8 )   S1506 - S1506   2021.8

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  • non-coding RNAを介したメトホルミンの抗線維化作用の解析

    近藤 星, 服部 高子, 桑原 実穂, Fu Shanqi, 西田 崇, 吉岡 洋祐, 森谷 徳文, 飯田 征二, 滝川 正春, 久保田 聡

    日本口腔科学会雑誌   70 ( 2 )   134 - 134   2021.7

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  • non-coding RNAを介したメトホルミンの抗線維化作用の解析

    近藤 星, 服部 高子, 桑原 実穂, Fu Shanqi, 西田 崇, 吉岡 洋祐, 森谷 徳文, 飯田 征二, 滝川 正春, 久保田 聡

    日本口腔科学会雑誌   70 ( 2 )   134 - 134   2021.7

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  • メトホルミンのUCA1誘導および軟骨細胞分化促進作用

    近藤星, 近藤星, 服部高子, 桑原実穂, FU Shanqi, 西田崇, 吉岡洋祐, 森谷徳文, 飯田征二, 滝川正春, 久保田聡

    日本生化学会大会(Web)   94th   2021

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  • Metformin promotes chondrocyte differentiation, which is accompanied by UCA1 induction.

    近藤星, 近藤星, 服部高子, 桑原実穂, FU Shanqi, 西田崇, 吉岡洋祐, 森谷徳文, 飯田征二, 滝川正春, 久保田聡

    日本分子生物学会年会プログラム・要旨集(Web)   44th   2021

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  • 変形性肩関節症とCCN3発現上昇との相関について

    廣瀬一樹, 中田英二, 服部高子, 鉄永智紀, 山田和希, 佐藤嘉洋, 桑原実穂, 滝川正春, 久保田聡, 尾崎敏文

    移植(Web)   56 ( 4 )   2021

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  • CCN6の破骨細胞形成における阻害作用

    西田崇, 西田崇, 芳地浩彰, 青山絵理子, 滝川正春, 久保田聡

    日本骨代謝学会学術集会プログラム抄録集(CD-ROM)   39th   2021

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  • Involvement of hippo pathway in the biological function of CCN2, CCN3 and PDGFRL in chondrocytes.

    河田かずみ, 青山絵理子, 滝川正春, 滝川正春, 久保田聡

    日本分子生物学会年会プログラム・要旨集(Web)   44th   2021

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  • The role and expression of C-type lectin CD302 in osteoblasts

    青山絵理子, 久保田聡, 滝川正春

    日本分子生物学会年会プログラム・要旨集(Web)   44th   2021

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  • C型レクチン様受容体CD302の骨芽細胞における発現と機能

    青山絵理子, 久保田聡, 滝川正春

    日本生化学会大会(Web)   94th   2021

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  • メトホルミンの軟骨細胞分化に対する作用の解析

    近藤 星, 服部 高子, 桑原 実穂, Fu Shanqi, 森谷 徳文, 飯田 征二, 滝川 正春, 久保田 聡

    岡山歯学会雑誌   39 ( 2 )   36 - 36   2020.12

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  • LIPUSによる脂肪細胞分化の抑制と骨芽細胞分化への影響

    西田 崇, 滝川 正春, 久保田 聡, 長尾 有里香, 橋谷 智子, 山中 信康

    日本骨代謝学会学術集会プログラム抄録集   38回   143 - 143   2020.10

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  • 軟骨細胞におけるエネルギー代謝不全時でのCCN3増産システムの解明

    水川 朋美, 西田 崇, 明石 翔, 上岡 寛, 滝川 正春, 久保田 聡

    日本骨代謝学会学術集会プログラム抄録集   38回   134 - 134   2020.10

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  • CCN2の核移行による線維化の制御

    西田 崇, 滝川 正春, 久保田 聡

    Journal of Oral Biosciences Supplement   2020   183 - 183   2020.9

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  • CCN3 as a chondrocytic aging-accelerating factor

    桑原実穂, 武内聡子, 近藤星, FU Shanqi, 大野充昭, 古松毅之, 中田英二, 滝川正春, 久保田聡, 服部高子

    日本軟骨代謝学会プログラム・抄録集   33rd   2020

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  • 軟骨組織におけるCCN3の老化促進作用

    桑原実穂, 桑原実穂, 近藤星, FU Shanqi, 大野充昭, 古松毅之, 中田英二, 皆木省吾, 滝川正春, 久保田聡, 服部高子

    日本分子生物学会年会プログラム・要旨集(Web)   43rd   2020

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  • S-adenosylmethionine enhances differentiation in chondrocytes via polyamine synthesis

    棚井あいり, 青山絵理子, 久保田聡, 滝川正春

    日本結合組織学会学術大会抄録集   52nd   2020

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  • S-adenosylmethionine promotes ECM production and proliferation of chondrocytes through polyamine synthesis

    青山絵理子, 久保田聡, 滝川正春

    Journal of Oral Biosciences Supplement (Web)   2020   2020

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  • フッ素イオンによるCCNファミリー遺伝子の制御

    水川 朋美, 西田 崇, 明石 翔, 堀 彩花, 高柴 正悟, 上岡 寛, 滝川 正春, 久保田 聡

    岡山歯学会雑誌   38 ( 2 )   85 - 85   2019.12

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  • CCNは軟骨細胞の加齢に伴い発現上昇し、過剰発現は軟骨加齢を促進する

    桑原 実穂, 武内 聡子, 近藤 星, Shanqi Fu, 大野 充昭, 古松 毅之, 中田 英二, 滝川 正春, 久保田 聡, 服部 高子

    岡山歯学会雑誌   38 ( 2 )   85 - 86   2019.12

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  • 低出力パルス超音波(LIPUS)の半月板修復効果とその作用機序 CCN2/CTGFの関与

    青山 絵理子, 西田 崇, 久保田 聡, 滝川 正春, 釜付 祐輔, 古松 毅之, 前原 亜美, 尾崎 敏文, 山中 信康

    Journal of Oral Biosciences Supplement   2019   403 - 403   2019.10

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  • 脂肪細胞分化に対する低出力パルス超音波(LIPUS)の抑制メカニズムの解明

    橋谷 智子, 西田 崇, 長尾 有里香, 滝川 正春, 久保田 聡

    Journal of Oral Biosciences Supplement   2019   418 - 418   2019.10

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  • 低出力性パルス超音波(LIPUS)による脂肪細胞分化の多面的抑制機構

    西田 崇, 長尾 有里香, 橋谷 智子, 山中 信康, 滝川 正春, 久保田 聡

    日本生化学会大会プログラム・講演要旨集   92回   [1P - 057]   2019.9

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  • Angiotensin IIによる軟骨変性作用とそのCCN2による制御機構

    西田 崇, 滝川 正春, 久保田 聡, 横井 秀基, 向山 政志

    日本骨代謝学会学術集会プログラム抄録集   37回   189 - 189   2019.9

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  • 軟骨細胞は加齢にともなってCCN3を高発現し,その過剰発現は軟骨加齢を促進する

    桑原実穂, 武内聡子, 近藤星, FU Shanqi, 大野充昭, 古松毅之, 中田英二, 滝川正春, 久保田聡, 服部高子

    日本分子生物学会年会プログラム・要旨集(Web)   42nd   2019

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  • 軟骨細胞の分化過程におけるCCN2の発現変動の意義

    村瀬友里香, 村瀬友里香, 村瀬友里香, 青山絵理子, 鈴木康弘, 佐々木朗, 久保田聡, 佐藤靖史, 滝川正春

    日本分子生物学会年会プログラム・要旨集(Web)   42nd   2019

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  • 低出力超音波パルス刺激による破骨細胞前駆細胞のアポトーシス誘導とそのメカニズム

    青山絵理子, 久保田聡, 山中信康, 滝川正春

    日本生化学会大会(Web)   92nd   2019

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  • 低出力パルス超音波(LIPUS)の半月板修復効果とその作用機序-CCN2/CTGFの関与

    青山絵理子, 西田崇, 西田崇, 久保田聡, 滝川正春

    Journal of Oral Biosciences Supplement (Web)   2019   2019

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  • CCN2とRab14の相互作用が骨・軟骨細胞の基質産生に及ぼす役割

    星島 光博, 服部 高子, 田中 智代, 上岡 寛, 滝川 正春

    日本矯正歯科学会大会プログラム・抄録集   77回   239 - 239   2018.10

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  • CCN2とRab14の相互作用が骨・軟骨細胞の小胞輸送に及ぼす役割 軟骨分化促進因子CCN2の新たな細胞内機能

    星島 光博, 服部 高子, 青山 絵理子, 西田 崇, 久保田 聡, 上岡 寛, 滝川 正春

    Journal of Oral Biosciences Supplement   2018   448 - 448   2018.9

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  • 癌の治療抵抗性と転移におけるHSP90およびMMP3の役割

    江口 傑徳, 小野 喜章, 奥舎 有加, 十川 千春, 内部 健太, 中野 敬介, 奥井 達雄, 滝川 正春, 岡元 邦彰, カルダーウッド・スチュアート

    Journal of Oral Biosciences Supplement   2018   142 - 142   2018.9

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  • 軟骨細胞におけるCCN3遺伝子の糖代謝を介した制御

    明石 翔, 西田 崇, El-Seoudi Abdellatif, 滝川 正春, 飯田 征二, 久保田 聡

    日本生化学会大会プログラム・講演要旨集   91回   [2P - 207]   2018.9

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  • 軟骨細胞、骨芽細胞分化にUCA1長鎖ノンコーディングRNAが与える影響

    石川 崇典, 西田 崇, 大野 充昭, 村瀬 友里香, 上岡 寛, 滝川 正春, 久保田 聡

    日本骨代謝学会学術集会プログラム抄録集   36回   172 - 172   2018.7

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  • 半月板に対する低出力パルス超音波(LIPUS)の効果

    釜付祐輔, 釜付祐輔, 青山絵理子, 古松毅之, 前原亜美, 山中信康, 西田崇, 久保田聡, 久保田聡, 尾崎敏文, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   31st   2018

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  • LIPUSが半月板に与える効果

    釜付祐輔, 釜付祐輔, 青山絵理子, 古松毅之, 前原亜美, 山中信康, 西田崇, 久保田聡, 久保田聡, 尾崎敏文, 滝川正春

    日本結合組織学会学術大会抄録集   50th   2018

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  • CCN2-VASH1-SOD2 axisを介した内軟骨性骨化調節機構

    村瀬友里香, 村瀬友里香, 村瀬友里香, 青山絵理子, 鈴木康弘, 佐々木朗, 久保田聡, 久保田聡, 佐藤靖史, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   31st   2018

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  • 癌の治療抵抗性と転移におけるHSP90およびMMP3の役割

    江口傑徳, 江口傑徳, 小野喜章, 小野喜章, 奥舎有加, 十川千春, 内部健太, 中野敬介, 中野敬介, 奥井達雄, 滝川正春, 岡元邦彰, CALDERWOOD SK

    Journal of Oral Biosciences Supplement (Web)   2018   2018

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  • 低出力超音波パルスによる破骨細胞分化の抑制とそのメカニズムの解明

    青山絵理子, 久保田聡, 久保田聡, 滝川正春

    Journal of Oral Biosciences Supplement (Web)   2018   2018

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  • 低出力超音波パルスによって誘導される破骨細胞前駆細胞の細胞死とTAZの活性化

    青山絵理子, 久保田聡, 久保田聡, 滝川正春

    日本骨代謝学会学術集会プログラム抄録集   36th   2018

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  • 低出力超音波パルスによる破骨細胞前駆細胞の成熟抑制メカニズムの解明

    青山絵理子, 久保田聡, 滝川正春

    日本分子生物学会年会プログラム・要旨集(Web)   41st   2018

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  • CCN2とRab14の相互作用が骨・軟骨細胞の小胞輸送に及ぼす役割

    星島 光博, 服部 高子, 青山 絵理子, 西田 崇, 田中 智代, 久保田 聡, 上岡 寛, 滝川 正春

    生命科学系学会合同年次大会   2017年度   [2P - 0285]   2017.12

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  • 細胞内におけるマトリックスメタロプロテアーゼ(MMP)の役割

    江口 傑徳, 奥舎 有加, 中野 敬介, 久保田 聡, 滝川 正春, カルダーウッド・スチュアート, 小崎 健一

    Journal of Oral Biosciences Supplement   2017   249 - 249   2017.9

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  • 軟骨細胞分化に関わる長鎖ノンコーディングRNAの骨形成における役割

    石川 崇典, 村瀬 友里香, 西田 崇, 服部 高子, 大野 充昭, 上岡 寛, 滝川 正春, 久保田 聡

    日本骨代謝学会学術集会プログラム抄録集   35回   166 - 166   2017.7

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  • 関節・成長板軟骨細胞におけるセロトニン(5-HT)によるCCN2産生の差別的制御メカニズム

    堀 綾花, 西田 崇, 高柴 正悟, 久保田 聡, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   35回   167 - 167   2017.7

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  • 骨格形成における低密度リポたんぱく質受容体関連たんぱく質1(LRP1)の役割

    河田かずみ, 久保田聡, 久保田聡, 服部高子, 青山絵理子, 滝川正春, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   30th   2017

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  • 内軟骨性骨化におけるvasohibin-1(VASH1)の発現とその意義

    村瀬友里香, 村瀬友里香, 村瀬友里香, 青山絵理子, 鈴木康弘, 佐々木朗, 久保田聡, 久保田聡, 佐藤靖史, 滝川正春

    日本生化学会大会(Web)   90th   2017

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  • 細胞内におけるマトリックスメタロプロテアーゼ(MMP)の役割

    江口傑徳, 江口傑徳, 奥舎有加, 中野敬介, 久保田聡, 滝川正春, CALDERWOOD SK, 小崎健一

    Journal of Oral Biosciences Supplement (Web)   2017   2017

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  • 3-2LIPUSにより半月板でのCCN2の発現・産生は増加する

    釜付祐輔, 釜付祐輔, 青山絵理子, 古松毅之, 前原亜美, 山中信康, 西田崇, 久保田聡, 久保田聡, 尾崎敏文, 滝川正春

    移植(Web)   52 ( 6 )   2017

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  • 低出力パルス超音波(LIPUS)が半月板中のCCN2,CCN3に与える効果

    釜付祐輔, 青山絵理子, 古松毅之, 前原亜美, 山中信康, 西田崇, 久保田聡, 久保田聡, 尾崎敏文, 滝川正春

    日本骨代謝学会学術集会プログラム抄録集   35th   2017

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  • 半月板におけるCCN2,CCN3に与える低出力パルス超音波(LIPUS)の効果

    釜付祐輔, 釜付祐輔, 青山絵理子, 古松毅之, 前原亜美, 山中信康, 西田崇, 久保田聡, 久保田聡, 尾崎敏文, 滝川正春

    日本結合組織学会学術大会抄録集   49th   2017

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  • CCN2とRab14の相互作用が軟骨細胞の小胞輸送に及ぼす役割

    星島 光博, 服部 高子, 滝川 正春, 上岡 寛

    日本矯正歯科学会大会プログラム・抄録集   75回   207 - 207   2016.11

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  • 骨格形成における低密度リポタンパク受容体関連タンパク1(LRP1)の役割

    KAWATA Kazumi, KUBOTA Satoshi, KUBOTA Satoshi, HATTORI Takako, AOYAMA Eriko, TAKIGAWA Masaharu, TAKIGAWA Masaharu

    日本骨代謝学会学術集会プログラム抄録集   34th   223 - 223   2016

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  • Investigation on long non‐coding RNAs that are associated with chondrocytic phenotype

    ISHIKAWA Takanori, MURASE Yurika, MURASE Yurika, NISHIDA Takashi, HATTORI Takako, TAKIGAWA Masaharu, KAMIOKA Hiroshi, KUBOTA Satoshi, KUBOTA Satoshi

    日本RNA学会年会要旨集   18th   ROMBUNNO.254   2016

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  • 軟骨細胞形質を支える長鎖非コードRNA

    石川崇典, 石川崇典, 久保田聡, 久保田聡, 村瀬友里香, 西田崇, 服部高子, 滝川正春, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   29th   2016

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  • 軟骨細胞形質に関わる長鎖非コードRNAの探索

    石川崇典, 石川崇典, 村瀬友里香, 西田崇, 服部高子, 滝川正春, 滝川正春, 上岡寛, 久保田聡, 久保田聡

    日本骨代謝学会学術集会プログラム抄録集   34th   2016

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  • 血小板に含まれるCCNファミリータンパク質の解析と軟骨再生への応用

    原規子, 原規子, 久保田聡, 久保田聡, 青山絵理子, 服部高子, 滝川正春, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   29th   2016

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  • フルオシノロンアセトニドは関節軟骨再生におけるTGF-β3誘導性軟骨細胞分化を相乗的に促進する

    HARA Emilio Satoshi, HARA Emilio Satoshi, 大野充昭, PHAM Hai Thanh, 園山亘, 久保田聡, 滝川正春, 松本卓也, YOUNG Marian F., OLSEN Bjorn R., 窪木拓男

    日本軟骨代謝学会プログラム・抄録集   29th   2016

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  • 軟骨細胞分化における癌抑制遺伝子PDGFR-like(PDGFRL)の役割

    河田かずみ, 久保田聡, 江口傑徳, 青山絵理子, 森谷徳文, 岡森彦, 川木晴美, 滝川正春, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   29th   2016

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  • 成熟破骨細胞のアクチンリング形成におけるCD302の機能とCCN2による制御

    青山 絵理子, 星島 光博, 服部 高子, 久保田 聡, 滝川 正春

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   88回・38回   [3T23 - 09(3P0069)]   2015.12

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  • 骨細胞の作用を介した破骨細胞形成におけるCCN2の役割

    西田 崇, 久保田 聡, 服部 高子, Bonewald Lynda F., 滝川 正春

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   88回・38回   [2P0151] - [2P0151]   2015.12

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  • Fluocinolone acetonideとTGF-β3を用いた強力な軟骨再生(Potent cartilage regeneration with fluocinolone acetonide and TGF-β3)

    Hara Emilio Satoshi, 大野 充昭, Pham Hai Thanh, 久保田 聡, 滝川 正春, Young Marian F., Olsen Bjorn R., 松本 卓也, 窪木 拓男

    日本バイオマテリアル学会大会予稿集   37回   209 - 209   2015.11

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  • Cellular and molecular actions of CCN2/CTGF and its role under physiological and pathological conditions (vo 128, pg 181, 2015)

    Satoshi Kubota, Masaharu Takigawa

    CLINICAL SCIENCE   129 ( 7 )   674 - 674   2015.10

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  • 破骨細胞分化における新規アクチン骨格制御因子としてのDCL-1/CD302の役割とCCN2との関連

    青山 絵理子, 星島 光博, 服部 高子, 久保田 聡, 滝川 正春

    Journal of Oral Biosciences Supplement   2015   230 - 230   2015.9

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  • CCN2は骨細胞を介して破骨細胞形成を制御する

    西田 崇, 久保田 聡, 服部 高子, 滝川 正春, Bonewald L.F.

    Journal of Oral Biosciences Supplement   2015   231 - 231   2015.9

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  • 糖質コルチコイドの中でfluocinolone acetonideはTGF-β3介在性BMSCの軟骨形成の活性化と関節の軟骨修復を促進において特異的な作用を有する(Among glucocorticoids, fluocinolone acetonide is unique in potentiating TGF-β 3-mediated chondrogenesis of BMSCs and promoting articular cartilage repair)

    Hara Emilio Satoshi, 大野 充昭, Pham Hai Thanh, Young Marian F., 久保田 聡, 滝川 正春, 窪木 拓男

    日本骨代謝学会学術集会プログラム抄録集   33回   161 - 161   2015.7

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  • 軟骨特異的CCN3過剰発現は内軟骨性骨化の遅延と関節変性を誘発する

    服部 高子, 角谷 宏一, 桑原 実穂, 大野 充昭, 星島 光博, 窪木 拓男, 久保田 聡, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   33回   158 - 158   2015.7

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  • CCN2による軟骨細胞のアミノ酸代謝制御

    村瀬友里香, 村瀬友里香, 服部高子, 青山絵理子, 西田崇, 前田彩, 川木晴美, 佐々木朗, 滝川正春, 久保田聡

    日本骨代謝学会学術集会プログラム抄録集   33rd   2015

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  • CCN2は骨細胞を介して破骨細胞形成を制御する

    西田崇, 久保田聡, 久保田聡, 服部高子, 滝川正春

    Journal of Oral Biosciences Supplement (Web)   2015   2015

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  • 骨軟骨再生因子CCN2の軟骨細胞アミノ酸代謝への影響

    村瀬友里香, 村瀬友里香, 服部高子, 青山絵理子, 前田彩, 川木晴美, 佐々木朗, 滝川正春, 久保田聡

    日本軟骨代謝学会プログラム・抄録集   28th   2015

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  • 新たな破骨細胞制御因子DCL-1/CD302の作用機構の解明とCCN2との関連

    青山絵理子, 服部高子, 星島光博, 星島光博, 久保田聡, 久保田聡, 滝川正春

    日本骨代謝学会学術集会プログラム抄録集   33rd   2015

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  • 破骨細胞分化における新規アクチン骨格制御因子としてのDCL-1/CD302の役割とCCN2との関連

    青山絵理子, 星島光博, 服部高子, 久保田聡, 久保田聡, 滝川正春

    Journal of Oral Biosciences Supplement (Web)   2015   2015

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  • 軟骨特異的CCN3過剰発現は軟骨の最終分化の遅延だけでなく、変形性関節症を誘発する

    服部 高子, 大野 充昭, 星島 光博, 角谷 宏一, 窪木 拓男, 滝川 正春

    Journal of Oral Biosciences Supplement   2014   125 - 125   2014.9

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  • 新たなCCN2結合因子DCL-1の破骨細胞分化における役割

    青山 絵理子, 星島 光博, 服部 高子, 久保田 聡, 滝川 正春

    Journal of Oral Biosciences Supplement   2014   105 - 105   2014.9

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  • 粉末食で飼育したマウスの下顎骨形態変化

    河野 加奈, 柳田 剛志, 久保田 聡, 滝川 正春, 上岡 寛, 山城 隆

    日本骨代謝学会学術集会プログラム抄録集   32回   314 - 314   2014.7

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  • E6-AP/UBE3AはSOX9のユビキチンリガーゼとして軟骨組織の分化を制御する

    服部高子, 木住野達也, STEPHEN Shelley, EBERSPAECHER Heidi, 巻さゆみ, 滝川正春, DE CROMBRUGGHE Benoit, 安田秀世, 安田秀世

    日本生化学会大会(Web)   87th   2014

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  • 軟骨細胞にてエネルギー産生を支えるCCN2の新たな役割

    前田彩, 前田彩, 久保田聡, 久保田聡, 川木晴美, 河田かずみ, 三宅由晃, 服部高子, 西田崇, 森谷徳文, LYONS Karen M, 飯田征二, 滝川正春, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   27th   2014

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  • 軟骨分化促進因子CCN2の新たな細胞内機能:CCN2とRab14GTPaseの相互作用が軟骨細胞の小胞輸送に及ぼす役割

    星島光博, 星島光博, 服部高子, 青山絵理子, 西田崇, 上岡寛, 滝川正春

    日本骨代謝学会学術集会プログラム抄録集   32nd   2014

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  • CCN2結合因子DCL-1の破骨細胞分化制御因子としての役割

    青山絵理子, 服部高子, 滝川正春, 滝川正春

    日本骨代謝学会学術集会プログラム抄録集   32nd   2014

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  • 新たなCCN2結合因子DCL-1の破骨細胞分化における役割

    青山絵理子, 星島光博, 服部高子, 久保田聡, 滝川正春, 滝川正春

    Journal of Oral Biosciences Supplement (Web)   2014   2014

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  • Fibroblast growth factor-1が軟骨代謝に及ぼす多彩な影響

    ABD EL KADER Tarek, ABD EL KADER Tarek, 久保田聡, 西田崇, 古松毅之, 青山絵理子, 窪木拓男, 滝川正春, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   27th   2014

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  • 破骨細胞分化における新規CCN2結合タンパク質DCL-1の発現と機能

    青山絵理子, 星島光博, 服部高子, 久保田聡, 滝川正春

    日本生化学会大会(Web)   87th   2014

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  • SOX9のユビキチンリガーゼE6-AP/UBE3Aは正常な骨格形成に必須である

    服部高子, 木住野達也, SHELLEY Stephen, HEIDI Eberspaecher, 巻さゆみ, 滝川正春, 西田崇, 久保田聡, DE CROMBRUGGHE Benoit, 安田秀世, 安田秀世

    日本分子生物学会年会プログラム・要旨集(Web)   37th   2014

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  • 軟骨特異的CCN3過剰発現は軟骨の最終分化の遅延だけでなく,変形性関節症を誘発する

    服部高子, 大野充昭, 星島光博, 星島光博, 角谷宏一, 窪木拓男, 滝川正春

    Journal of Oral Biosciences Supplement (Web)   2014   2014

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  • E6-AP/UBE3AはSOX9のユビキチンリガーゼである

    服部高子, 木住野達也, STEPHEN Shelley, EBERSPAECHER Heidi, 巻さゆみ, 滝川正春, DE CROMBRUGGHE Benoit, 安田秀世, 安田秀世, 安田秀世

    日本軟骨代謝学会プログラム・抄録集   27th   2014

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  • 軟骨細胞における低出力超音波(LIPUS)とROCK阻害剤によるCCN2の相加的産生

    西田崇, 久保田聡, 青山絵理子, 山中信康, LYONS Karen M, 滝川正春, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   27th   2014

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  • 血小板に存在するCCNファミリーメンバーとその由来

    原規子, 原規子, 久保田聡, 久保田聡, 青山絵理子, 青山絵理子, 滝川正春, 滝川正春

    岡山歯学会雑誌   33 ( 2 )   2014

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  • CCN3の抗線維化効果に伴うCCNファミリー遺伝子発現プロファイルの変化

    アブド・エル・ケーダー・タレック, 久保田 聡, ジャヌネ・ダニーロ, 西田 崇, 服部 高子, 青山 絵理子, 窪木 拓男, 滝川 正春

    岡山歯学会雑誌   32 ( 2 )   83 - 83   2013.12

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  • 軟骨細胞の代謝の基本を支えるCCN2の重要性(Essential role of CCN2 that supports the basal energy metabolism in chondrocytes)

    前田 彩, 久保田 聡, 三宅 由晃, 河田 かずみ, 服部 高子, 西田 崇, 森谷 徳文, 川木 晴美, カレン・ライアン, 飯田 征二, 滝川 正春

    日本生化学会大会プログラム・講演要旨集   86回   2T06a - 15   2013.9

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  • 流体剪断応力により重合したアクチンによりCCN2の発現と骨芽細胞の分化は誘導される

    本城 正, 久保田 聡, 上岡 寛, 山城 隆, 滝川 正春, 山本 照子

    Journal of Oral Biosciences Supplement   2013   203 - 203   2013.9

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  • CCNファミリー研究のメルティングポット ERK1/2経路を介したCCN3の初期軟骨分化における作用の検討

    川木 晴美, 久保田 聡, 尾上 一平, 近藤 雄三, 高橋 潤, 神谷 真子, 高山 英次, 近藤 信夫, 滝川 正春

    Journal of Oral Biosciences Supplement   2013   94 - 94   2013.9

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  • CCNファミリー遺伝子の発現プロフィールの操作を介したCCN3の線維化抑制作用の理解(Understanding the anti-fibrotic role of CCN3 through manipulation of CCN family gene expression profile)

    El Kader Tarek Abd, Kubota Satoshi, Janune Danilo, Nishida Takashi, Hattori Takako, Aoyama Eriko, Perbal Bernard, Kuboki Takuo, Takigawa Masaharu

    日本生化学会大会プログラム・講演要旨集   86回   1T11a - 15   2013.9

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  • CCNファミリー研究のメルティングポット 軟骨特異切CCN3過剰発現による内軟骨性骨形成の修飾

    服部 高子, 大野 充昭, 星島 光博, 角谷 宏一, 桑原 実穂, 三宅 佳子, 窪木 拓男, 滝川 正春

    Journal of Oral Biosciences Supplement   2013   94 - 94   2013.9

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  • 軟骨細胞と変形性関節症モデルを用いたCCN2各モジュールの組織再生効果の評価

    El Kader Tarek Abd, 久保田 聡, 西田 崇, 服部 高子, 青山 絵里子, Danilo Janune, 窪木 拓男, 滝川 正春

    Journal of Oral Biosciences Supplement   2013   123 - 123   2013.9

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  • CCN3の抗線維化効果に伴うCCNファミリー遺伝子発現プロファイルの変化

    Danilo Janune, El Kader Tarek Abd, 久保田 聡, 西田 崇, 服部 高子, 青山 絵里子, 窪木 拓男, 滝川 正春

    Journal of Oral Biosciences Supplement   2013   126 - 126   2013.9

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  • CCN3の軟骨特異的過剰発現は内軟骨性骨形成の遅延を誘発する

    角谷 宏一, 服部 高子, 桑原 実穂, 大野 充昭, 星島 光博, 窪木 拓男, 滝川 正春

    Journal of Oral Biosciences Supplement   2013   138 - 138   2013.9

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  • 粉末食を与えて飼育したマウスの下顎骨形態変化

    柳田 剛志, 久保田 聡, 滝川 正春, 山城 隆

    Journal of Oral Biosciences Supplement   2013   147 - 147   2013.9

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  • CCNファミリー研究のメルティングポット CCN2は軟骨細胞のエネルギー代謝に重要である

    前田 彩, 久保田 聡, 川木 晴美, 河田 かずみ, 三宅 由晃, 服部 高子, 西田 崇, 森谷 徳文, 飯田 征二, 滝川 正春

    Journal of Oral Biosciences Supplement   2013   95 - 95   2013.9

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  • Impaired glycolytic metabolism causes chondrocyte hypertrophy-like changes via promotion of phospho-Smad1/5/8 translocation into nucleus.

    Nishida T, Kubota S, Aoyama E, Takigawa M

    Osteoarthritis Cartilage   21   700 - 709   2013

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  • CCN2は軟骨細胞のエネルギー代謝に重要である

    前田彩, 前田彩, 久保田聡, 川木晴美, 河田かずみ, 三宅由晃, 服部高子, 西田崇, 森谷徳文, 飯田征二, 滝川正春

    Journal of Oral Biosciences Supplement (Web)   2013   ROMBUNNO.SS9‐5 (WEB ONLY)   2013

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  • Regulation of CCN1 via the 3’-untranslated region.

    Nakagawa Y, Minato M, Sumiyoshi K, Maeda A, Hara C, Murase Y, Nishida T, Kubota S, Takigawa M

    J. Cell Commun. Signal.   7   207 - 217   2013

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  • 軟骨細胞のエネルギー代謝を支えるCCN2/CTGF

    前田彩, 前田彩, 久保田聡, 三宅由晃, 河田かずみ, 西田崇, 服部高子, 森谷徳文, 川木晴美, LYONS Karen M., 飯田征二, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   26th   2013

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  • 軟骨特異的CCN3過剰発現による内軟骨性骨形成の修飾

    服部高子, 大野充昭, 星島光博, 角谷宏一, 桑原実穂, 三宅佳子, 窪木拓男, 滝川正春

    Journal of Oral Biosciences Supplement (Web)   2013   2013

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  • CCN3の抗線維化効果に伴うCCNファミリー遺伝子発現プロファイルの変化

    DANILO Janune, ABD EL KADER Tarek, ABD EL KADER Tarek, 久保田聡, 西田崇, 服部高子, 青山絵里子, 窪木拓男, 滝川正春, 滝川正春

    Journal of Oral Biosciences Supplement (Web)   2013   2013

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  • 軟骨特異的CCN3過剰発現は内軟骨性骨形成の不全より骨異形性を誘発する

    服部高子, 大野充昭, 星島光博, 角谷宏一, 桑原実穂, 三宅佳子, 窪木拓男, 滝川正春

    日本分子生物学会年会プログラム・要旨集(Web)   36th   2013

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  • CCN3の軟骨特異的過剰発現は内軟骨性骨形成の遅延を誘発する

    角谷宏一, 服部高子, 桑原実穂, 大野充昭, 星島光博, 窪木拓男, 滝川正春

    Journal of Oral Biosciences Supplement (Web)   2013   2013

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  • 軟骨特異的CCN3過剰発現は内軟骨性骨形成の遅延による骨梁形成の低下を誘発する

    服部高子, 大野充昭, 星島光博, 角谷宏一, 桑原実穂, 大家遥, 三宅佳子, 窪木拓男, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   26th   2013

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  • CCN2を構成する各モジュールの軟骨再生効果

    ABD EL KADER Tarek, ABD EL KADER Tarek, 久保田聡, 西田崇, 服部高子, 青山絵理子, JANUNE Danilo, 窪木拓男, 滝川正春, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   26th   2013

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  • グルココルチコイド薬フルオシノロンアセトニドはAKT/mTORシグナル経路を介し骨髄由来間葉系間質細胞の軟骨分化を増強する

    HARA Emilio Satoshi, 大野充昭, 久保田聡, 園山亘, PHAM Hai Thanh, 滝川正春, 窪木拓男

    日本軟骨代謝学会プログラム・抄録集   26th   2013

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  • Rab14GTPaseのCCN2/CTGF結合因子としての同定と,これらの相互作用が軟骨細胞の小胞輸送に及ぼす役割

    星島光博, 星島光博, 服部高子, 青山絵理子, 西田崇, 山城隆, 滝川正春, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   26th   2013

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  • Rab14GTPaseのCCN2/CTGF結合因子としての同定,およびこれらの相互作用が軟骨細胞の小胞輸送に及ぼす役割

    星島光博, 星島光博, 服部高子, 青山絵理子, 西田崇, 滝川正春, 滝川正春

    Journal of Oral Biosciences Supplement (Web)   2013   2013

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  • CCN3/NOVの軟骨特異的過剰発現は軟骨分化の最終段階に影響を及ぼす事により骨形成不全をきたす

    服部 高子, 大野 充昭, 星島 光博, 角谷 宏一, 桑原 実穂, 三宅 佳子, 窪木 拓男, 滝川 正春

    日本生化学会大会プログラム・講演要旨集   85回   3T02 - 08   2012.12

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  • 軟骨組織特異的低密度リポタンパク受容体欠損マウスにおける骨格形成(Deficiency of the low-density lipoprotein receptor related protein 1 (LRP1) in the cartilaginous tissue leads to skeletal dysmorphisms)

    河田 かずみ, 久保田 聡, 服部 高子, 青山 絵理子, ダニーロ・ジャヌネ, 滝川 正春

    日本生化学会大会プログラム・講演要旨集   85回   3P - 668   2012.12

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  • CCN2非依存性モジュールの軟骨再生能力(Cartilage regeneration potential of CCN2 independent modules)

    El Kader Tarek Abd, Kubota Satoshi, Nishida Takashi, Hattori Takako, Aoyama Eriko, Janune Danilo, Kuboki Takuo, Takigawa Masaharu

    日本再生歯科医学会誌   10 ( 1 )   50 - 50   2012.12

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  • Effect of CCN2/CTGF on FGF2-induced proliferation of and MMP-9 and-13 productions by chondrocytes

    T. Nishida, S. Kubota, E. Aoyama, D. Janune, A. Maeda, M. Takigawa

    FEBS JOURNAL   279   169 - 169   2012.9

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  • 初期軟骨分化におけるCCN3の機能解析

    川木 晴美, 久保田 聡, 尾上 一平, 近藤 雄三, 神谷 真子, 高山 英次, 近藤 信夫, 滝川 正春

    Journal of Oral Biosciences Supplement   2012   162 - 162   2012.9

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  • CCN2/CTGF欠損が軟骨細胞のエネルギー代謝に及ぼす影響

    前田 彩, 久保田 聡, 服部 高子, 西田 崇, 飯田 征二, 滝川 正春

    Journal of Oral Biosciences Supplement   2012   96 - 96   2012.9

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  • Glyceraldehyde-3-phosphate dehydrogenaseはCCN2mRNA結合蛋白である(Binding of GAPDH to the cis-acting element of structure-anchored repression in ccn2 mRNA)

    近藤 誠二, 久保田 聡, 吉濱 泰斗, 新谷 悟, 滝川 正春

    日本癌学会総会記事   71回   465 - 465   2012.8

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  • 軟骨細胞と骨芽細胞に対するCCN2独立モジュールの影響(Effects of CCN2 independent modules on chondrocytic and osteoblastic cells)

    El Kader Tarek Abd, Kubota Satoshi, Nishida Takashi, Hattori Takako, Aoyama Eriko, Janune Danilo, Kuboki Takuo, Takigawa Masaharu

    日本骨代謝学会学術集会プログラム抄録集   30回   232 - 232   2012.7

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  • Roles of CCN2 in energy metabolism in chondrocytes.

    A. Maeda, S. Kubota, Y. Miyake, K. Kawata, T. Nishida, T. Hattori, N. Moritani, H. Kawaki, K. M. Lyons, S. Iida, M. Takigawa

    MOLECULAR BIOLOGY OF THE CELL   23   2012

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  • Roles of the heterotypic CCN2-CCN3 and homotypic CCN2-CCN2 interactions in matrix synthesis in chondrocytes.

    M. Hoshijima, T. Hattori, E. Aoyama, T. Nishida, T. Yamashiro, M. Takigawa

    MOLECULAR BIOLOGY OF THE CELL   23   2012

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  • 軟骨細胞のエネルギー代謝におけるCCN2/CTGFの役割

    前田彩, 前田彩, 久保田聡, 三宅由晃, 河田かずみ, 西田崇, 服部高子, 森谷徳文, 川木晴美, LYONS Karen M., 飯田征二, 滝川正春

    日本分子生物学会年会プログラム・要旨集(Web)   35th   2012

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  • CCN2/CTGF欠損が軟骨細胞のエネルギー代謝に及ぼす影響

    前田彩, 前田彩, 久保田聡, 服部高子, 西田崇, 飯田征二, 滝川正春

    Journal of Oral Biosciences Supplement (Web)   2012   2012

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  • 軟骨細胞の代謝システムにおけるCCN2の役割

    前田彩, 前田彩, 久保田聡, 三宅由晃, 河田かずみ, 服部高子, 西田崇, 森谷徳文, 川木晴美, LYONS Karen M., 飯田征二, 滝川正春

    岡山歯学会雑誌   31 ( 2 )   2012

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  • 軟骨分化促進作用を有するグルココルチコイド薬フルオシノロンアセトニド

    HARA Emilio Satoshi, 大野充昭, 久保田聡, 園山亘, 藤澤拓生, 滝川正春, 窪木拓男

    日本軟骨代謝学会プログラム・抄録集   25th   2012

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  • 骨芽細胞分化におけるCCNファミリータンパク質の分布と機能解析

    川木晴美, 久保田聡, 鈴木晶子, 星健治, 高山英次, 神谷真子, 前田健康, 山本照子, 近藤信夫, 滝川正春

    J Oral Biosci   53 ( Supplement )   116 - 116   2011.9

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  • CCN2/CTGFとCCN3/NOVのヘテロおよびホモダイマー形成が軟骨細胞の基質合成に及ぼす役割

    星島 光博, 服部 高子, 西田 崇, 山城 隆, 滝川 正春

    Journal of Oral Biosciences   53 ( Suppl. )   141 - 141   2011.9

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  • 軟骨細胞における血小板由来増殖因子受容体様(PDGFRL)遺伝子の発現(Expression of platelet-derived growth factor receptor-like (PDGFRL) gene in chondrocytes)

    河田 かずみ, 久保田 聡, 江口 傑徳, 青山 絵理子, 森谷 徳文, 岡 森彦, 川木 晴美, 滝川 正春

    日本生化学会大会プログラム・講演要旨集   84回   3P - 0351   2011.9

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  • CCN2/CTGFとCCN3/NOVのヘテロダイマー、およびCCN2のホモダイマー形成が軟骨細胞の基質合成に及ぼす役割

    星島 光博, 服部 高子, 青山 絵理子, 西田 崇, 山城 隆, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   29回   247 - 247   2011.7

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  • CCN2/CTGF誘導因子であるハルミンは軟骨形成を促進し、TNF-α誘発炎症反応を抑制する(HARMINE, AN INDUCER OF CCN2/CTGF, PROMOTES CHONDROGENESIS AND SUPPRESSES TNF-α-INDUCED INFLAMMATORY RESPONSE)

    Hara Emilio S.i, Ono Mitsuaki, Kubota Satoshi, Sonoyama Wataru, Hattori Takako, Takigawa Masaharu, Kuboki Takuo

    日本骨代謝学会学術集会プログラム抄録集   29回   232 - 232   2011.7

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  • 軟骨細胞に対する、CCN2モジュールの単独・結合下での影響に関する評価(Evaluation of independent and combinational effect of CCN2 modules on chondorocytic cells)

    El Kdaer Tarek Abd, Kubota Satoshi, Nishida Takashi, Hattori Takako, Aoyama Eriko, Janune Danilo, Kuboki Takuo, Takigawa Masaharu

    日本骨代謝学会学術集会プログラム抄録集   29回   248 - 248   2011.7

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  • CCN2/CTGF promotes osteoclastogenesis via induction of and interaction with dendritic cell-specific transmembrane protein (DC-STAMP)

    T. Nishida, K. Emura, S. Kubota, K. M. Lyons, M. Takigawa

    FEBS JOURNAL   278   147 - 147   2011.6

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  • 低密度リポタンパク受容体関連タンパク1(LRP1)による軟骨細胞でのCCNファミリー2/結合組織成長因子(CCN2/CTGF)タンパク質輸送

    河田 かずみ, 久保田 聡, 江口 傑徳, 青山 絵理子, 近藤 誠二, 滝川 正春

    日本結合組織学会学術大会・マトリックス研究会大会合同学術集会プログラム・抄録集   43回・58回   76 - 76   2011.5

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  • 結合組織成長因子CCN2/CTGFは頭部神経堤由来の軟骨細胞分化に必須である

    服部高子, 寺岡徳光, 寺岡徳光, GEBHARDT Matthias, GEBHARDT Matthias, 内田瑶子, 内田瑶子, 新村兆一郎, 新村兆一郎, 福原大樹, 福原大樹, 滝川正春

    日本分子生物学会年会プログラム・要旨集(Web)   34th   2011

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  • マウス成長板におけるCa2+結合タンパクsorcinの局在について

    河井まりこ, 服部高子, 滝川正春, 山本敏男

    Journal of Oral Biosciences   53 ( Supplement )   2011

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  • Receptor activator of NF-κB(RANK)結合タンパク質であるCCN2/CTGFのRANKL誘導性破骨細胞形成における機能

    青山絵理子, 久保田聡, 西田崇, 滝川正春, 滝川正春

    岡山歯学会雑誌   30 ( 2 )   2011

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  • マイクロRNAによる軟骨細胞形質制御とCCN1(Cyr61)の関与

    住吉 久美, 久保田 聡, 大河原 敏博, 志茂 剛, 河田 かずみ, 西田 崇, 山城 隆, 滝川 正春

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   83回・33回   3P - 0760   2010.12

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  • FGF2刺激による軟骨細胞増殖促進及びMMP13酵素活性上昇に与えるCCN2/CTGFの影響

    西田 崇, 粕山 拓郎, 前田 あずさ, 青山 絵理子, 久保田 聡, 滝川 正春

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   83回・33回   1P - 0291   2010.12

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  • 軟骨細胞のCCN2蛋白質輸送における低比重リポ蛋白受容体関連蛋白質1(LRP1)の役割(Role of the low-density lipoprotein receptor related protein 1 (LRP1) in CCN2 protein transportation in chondrocytes)

    河田 かずみ, 久保田 聡, 江口 傑徳, 青山 絵理子, 近藤 誠二, 滝川 正春

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   83回・33回   2T10 - 12   2010.12

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  • CCN2/CTGFのホモダイマー形成、およびCCN3/NOVとのヘテロダイマーの形成と、それらが軟骨細胞の基質合成に及ぼす役割

    星島 光博, 服部 高子, 青山 絵理子, 西田 崇, 山城 隆, 滝川 正春

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   83回・33回   2P - 0101   2010.12

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  • 軟骨組織特異的CCN2/CTGF過剰発現による膝関節軟骨の加齢変性抑制効果

    伊藤 慎将, 服部 高子, 青山 絵理子, 山城 隆, 滝川 正春

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   83回・33回   4P - 1007   2010.12

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  • CCN1遺伝子転写後調節に関与するmiRNAの機能解析

    住吉 久美, 久保田 聡, 西田 崇, 山城 隆, 滝川 正春

    Journal of Oral Biosciences   52 ( Suppl )   133 - 133   2010.9

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  • 軟骨組織特異的CCN2/CTGF過剰発現によりマウスの膝関節軟骨は加齢後もより正常に近い形質を維持する

    伊藤 慎将, 服部 高子, 山城 隆, 滝川 正春

    Journal of Oral Biosciences   52 ( Suppl )   136 - 136   2010.9

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  • CCN2/CTGF Modulates BMP Signaling as a Signal Conductor, Which Action Regulates the Proliferation and Differentiation of Chondrocytes

    MAEDA A, NISHIDA T, KUBOKI T, TAKIGAWA M

    1 ( 118 )   225 - 225   2010.8

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  • マイクロRNA181-aによる軟骨細胞形質の制御とCCN1の関与

    住吉 久美, 久保田 聡, 大河原 敏博, 志茂 剛, 河田 かずみ, 西田 崇, 山城 隆, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   28回   249 - 249   2010.7

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  • CCN2/CTGFのホモダイマー形成、およびCCN3/NOVとのヘテロダイマーの形成とそれらの軟骨細胞における生理作用

    星島 光博, 服部 高子, 青山 絵理子, 西田 崇, 山城 隆, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   28回   260 - 260   2010.7

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  • 低密度リポタンパク受容体関連タンパク1(LRP1)による軟骨細胞でのタンパク質輸送

    河田 かずみ, 久保田 聡, 江口 傑徳, 青山 絵理子, 近藤 誠二, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   28回   188 - 188   2010.7

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  • CCN2/CTGFとCCN2/CTGFおよびCCN3/NOVとの結合とそれらの相互作用の解析

    星島 光博, 服部 高子, 青山 絵理子, 西田 崇, 山城 隆, 滝川 正春

    岡山歯学会雑誌   29 ( 1 )   74 - 74   2010.6

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  • Possible role of CCN family members during osteoblast differentiation.

    Kawaki H, Suzuki M, Fujii T, Takigawa M, Takano-Yamamoto T

    Interface Oral Health Science 2009.   2010

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  • 軟骨特異的CCN2/CTGF過剰発現による膝関節軟骨の加齢に伴う変性抑制効果

    伊藤慎将, 伊藤慎将, 服部高子, 冨田奈緒, 冨田奈緒, 青山絵理子, 山城隆, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   23rd   2010

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  • CCN2/CTGFの核内移行とExportin-1による核-細胞質間分子輸送

    服部高子, 星島光博, 荒木大介, 青山絵理子, 滝川正春

    日本骨代謝学会学術集会プログラム抄録集   28th   2010

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  • Exportin-1によるCCN2/CTGFの核-細胞質間分子輸送とその生理的意義

    内田瑶子, 服部高子, 荒木大介, 滝川正春

    Journal of Oral Biosciences   52 ( Supplement )   2010

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  • CCN2/CTGFはマトリリン-3と結合して軟骨マトリックス成分のネットワーク形成を促進する

    服部高子, 荒木大介, 星島光博, 青山絵理子, 新村兆一郎, OTTEN Christiane, WAGENER Raimund, 滝川正春

    生化学   2010

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  • Sox9は血管侵入,骨髄形成および内軟骨性骨形成の最終段階を抑制する-Col10a1-BACトランスジェニックマウスを用いた解析-

    服部高子, 池側広志, 小郷絢子, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   23rd   2010

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  • CCN2/CTGFはマトリリン-3と結合して軟骨マトリックス成分のネットワーク形成を促進する

    服部高子, 荒木大介, 星島光博, 青山絵理子, 新村兆一郎, OTTEN Christiane, WAGENER Raimund, 滝川正春

    日本結合組織学会学術大会抄録集   42nd   2010

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  • 軟骨細胞におけるCCN2遺伝子の転写後調節機構におけるNucleophosmin/B23の機能的意義

    住吉 久美, 久保田 聡, 椋代 義樹, 近藤 誠二, 川木 晴美, 江口 傑徳, 大河原 敏博, 山城 隆, 滝川 正春

    日本生化学会大会プログラム・講演要旨集   82回   3T18a - 8   2009.9

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  • 軟骨特異的CCN2/CTGF過剰発現マウスは膝関節軟骨の加齢性変化に抵抗性を示す

    伊藤 慎将, 服部 高子, 冨田 奈緒, 青山 絵里子, 山城 隆, 滝川 正春

    日本生化学会大会プログラム・講演要旨集   82回   2T5a - 4   2009.9

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  • 軟骨特異的CCN2/CTGF過剰発現は膝関節軟骨を加齢に伴う変性から保護する

    伊藤 慎将, 服部 高子, 青山 絵里子, 山城 隆, 滝川 正春

    Journal of Oral Biosciences   51 ( Suppl. )   105 - 105   2009.8

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  • Nucleophosmin/B23によるChicken CCN2遺伝子の軟骨細胞特異的転写後調節

    住吉 久美, 久保田 聡, 椋代 義樹, 近藤 誠二, 川木 晴美, 江口 傑徳, 山城 隆, 滝川 正春

    Journal of Oral Biosciences   51 ( Suppl. )   105 - 105   2009.8

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  • 成長板軟骨細胞後期分化に関与するマイクロRNAの探索

    住吉 久美, 久保田 聡, 大河原 敏博, 志茂 剛, 山城 隆, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   27回   174 - 174   2009.7

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  • 軟骨特異的CCN2/CTGF過剰発現は関節軟骨を加齢に伴う変形性関節炎様変化から防御する

    伊藤 慎将, 服部 高子, 冨田 奈緒, 青山 絵理子, 山城 隆, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   27回   249 - 249   2009.7

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  • CCNファミリー2/結合組織成長因子(CCN2/CTGF)はDC-STAMPの遺伝子発現レベルの上昇を介して破骨細胞形成を促進する

    西田 崇, 江村 憲資, 久保田 聡, 前田 あずさ, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   27回   216 - 216   2009.7

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  • 低密度リポタンパク受容体関連タンパク-1(LRP1)の軟骨細胞分化における機能とその作用機構

    河田 かずみ, 久保田 聡, 江口 傑徳, 青山 絵理子, 森谷 徳文, 近藤 誠二, 西田 崇, 皆木 省吾, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   27回   179 - 179   2009.7

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  • CCN2/CTGF has anti-aging effects to protect articular cartilage from age-related degenerative changes

    S. Itoh, T. Hattori, N. Tomita, E. Aoyama, T. Yamashiro, M. Takigawa

    BONE   44   S47 - S47   2009.5

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    DOI： 10.1016/j.bone.2009.01.121

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  • Micro RNA 18a regulates chondrocytic phenotype: Involvement of Ccn2/Ctgf as a major target gene

    T. Ohgawara, S. Kubota, H. Kawaki, S. Kondo, T. Eguchi, A. Sasaki, M. Takigawa

    BONE   44   S42 - S43   2009.5

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    DOI： 10.1016/j.bone.2009.01.109

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  • 岡山大学歯学部戦略的計画 －求められている今後の対応策－

    松香芳三, 池亀美華, 吉田登志子, 有馬太郎, 皆木省吾, 山本敏男, 高柴正悟, 窪木拓男, 北山滋雄, 滝川正春, 松尾龍二

    岡山歯学会雑誌   28 ( 2 )   123 - 130   2009

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  • CCNファミリー2/結合組織成長因子はBMPシグナルを修飾し,軟骨細胞増殖・分化を制御する

    前田あずさ, 前田あずさ, 西田崇, 青山絵理子, 久保田聡, 窪木拓男, LYONS Karen, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   22nd   2009

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  • 軟骨特異的CCN2/CTGF過剰発現マウスは膝関節軟骨の加齢に伴う変形性関節症様軟骨変化が抑制され,より正常に近い形質を維持する

    伊藤慎将, 伊藤慎将, 服部高子, 冨田奈緒, 青山絵里子, 山城隆, 滝川正春

    日本分子生物学会年会講演要旨集   32nd ( Vol.4 )   2009

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  • CCN2/CTGFの軟骨特異的過剰発現は加齢に伴う膝関節軟骨の変性に対して抑制的に働く

    伊藤慎将, 伊藤慎将, 服部高子, 冨田奈緒, 冨田奈緒, 青山絵里子, 青山絵里子, 山城隆, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   22nd   2009

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  • 軟骨細胞においてMMP3は核移行しCCN2/CTGFの転写活性化因子として働く

    江口傑徳, 江口傑徳, 久保田聡, 河田かずみ, 椋代義樹, 上原淳二, 大河原敏博, 大河原敏博, 伊原木聰一郎, 佐々木朗, 窪木拓男, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   22nd   2009

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  • CCN2/CTGFのExportin-1による核-細胞質間分子輸送

    服部高子, 小郷絢子, 圓城裕基, 池側広志, 荒木大介, 星島光博, 青山絵理子, 滝川正春

    日本分子生物学会年会講演要旨集   32nd ( Vol.1 )   2009

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  • CCN2/CTGFと結合するタンパク質の同定

    星島光博, 服部高子, 荒木大介, 青山絵理子, 西田崇, 滝川正春

    岡山歯学会雑誌   28 ( 1 )   2009

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  • Sox9は軟骨において血管侵入を抑制する事によって内軟骨性骨形成の最終段階である骨髄形成を抑制する-Col10a1-BACトランスジェニックマウスを用いた解析-

    服部高子, 池側広志, 小郷絢子, 滝川正春

    生化学   2009

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  • CCN2/CTGFとBMP-2の相互作用が軟骨細胞の増殖と分化を制御する

    西田 崇, 前田 あずさ, 青山 絵理子, 久保田 聡, 窪木 拓男, Lyons Karen, 滝川 正春

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   81回・31回   3T13 - 4   2008.11

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  • CCN2/CTGFの関節軟骨アンチエイジング作用 軟骨組織特異的CCN2/CTGF過剰発現マウスを用いた解析

    伊藤 慎将, 服部 高子, 冨田 奈緒, 青山 絵理子, 山城 隆, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   26回   177 - 177   2008.10

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  • CCN2/CTGFによるBMP-2の軟骨細胞増殖・分化促進作用の制御

    前田 あずさ, 西田 崇, 青山 絵理子, 川木 晴美, 久保田 聡, 窪木 拓男, ライアン・カレン, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   26回   234 - 234   2008.10

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  • マイクロRNA 18aによるCcn2/Ctgf遺伝子を介した軟骨細胞分化の制御機構の解明

    大河原 敏博, 久保田 聡, 川木 晴美, 近藤 誠二, 江口 傑徳, 佐々木 朗, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   26回   168 - 168   2008.10

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  • CCN2/CTGFの軟骨特異的過剰発現が内軟骨性骨化に及ぼす影響

    冨田 奈緒, 服部 高子, 伊藤 慎将, 青山 絵理子, 矢尾 真弓, 山城 隆, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   26回   168 - 168   2008.10

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  • Overexpression of CCN2/CTGF in Cartilage Shows Prolonged Bone Length Resulting from Stimulation of Chondrogenesis, Chondrocyte Growth, Apoptosis, and Bone Mineralization During Endochondral Ossification.

    N. Tomita, T. Hattori, S. Ito, E. Aoyama, M. Yao, T. Yamashiro, M. Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   23   S411 - S411   2008.9

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  • CCN2/CTGF軟骨特異的過剰発現が骨格形成に及ぼす影響

    冨田 奈緒, 服部 高子, 伊藤 慎将, 青山 絵理子, 山城 隆, 滝川 正春

    Journal of Oral Biosciences   50 ( Suppl. )   148 - 148   2008.9

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  • 乳癌および軟骨肉腫細胞におけるMicro RNA 18aのCCN2遺伝子発現抑制様態の比較解析(Comparative analysis of micro RNA 18a and CCN2 gene expression in breast cancer and chondrosarcoma cells)

    大河原 敏博, 久保田 聡, 近藤 誠二, 佐々木 朗, 滝川 正春

    日本癌学会総会記事   67回   305 - 305   2008.9

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  • CCN2/CTGF軟骨特異的過剰発現マウスの作製とその硬組織の解析

    冨田 奈緒, 服部 高子, 伊藤 慎将, 青山 絵里子, 矢尾 真弓, 山城 隆, 滝川 正春

    生化学   80 ( 7 )   694 - 694   2008.7

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  • CCN2欠損マウスを用いた,CCN2およびCCN3によるPTHrP‐Ihhループを介した軟骨細胞分化制御機構の解析

    川木晴美, 久保田聡, 鈴木晶子, 前田健康, 山本照子, 滝川正春

    日本骨代謝学会学術集会プログラム抄録集   26th   143   2008

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  • EBMワークショップと大学院教育の実質化

    松香芳三, 福岡敏雄, 完山 学, 前川賢治, 荒川 光, 水口 一, 園山 亘, 上原淳二, 縄稚久美子, 山崎聖也, 窪木拓男, 滝川正春, 松尾龍二, 田中紀章

    岡山歯学会雑誌   27 ( 1 )   43 - 49   2008

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  • ノックアウトマウスを用いた顎顔面形成における軟骨由来成長因子CCN2/CTGFの機能解析

    川木晴美, 久保田聡, 鈴木晶子, 前田健康, LYONS Karen M, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   21st   96   2008

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  • 軟骨特異的CCN2/CTGF過剰発現は骨延長を誘導する

    服部高子, 冨田奈緒, 冨田奈緒, 伊藤慎将, 伊藤慎将, 青山絵理子, 矢尾真弓, 山城隆, 滝川正春

    生化学   2008

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  • 軟骨成長・分化因子CCN2/CTGFはマトリリン3に結合する事によってマトリックスのネットワーク形成を促進する

    荒木大介, 服部高子, 青山絵理子, 星島光博, 滝川正春

    Journal of Oral Biosciences   50 ( Supplement )   2008

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  • CCN2/CTGFとBMP-2との分子間相互作用はヒト軟骨細胞様細胞株HCS-2/8の細胞分化を制御する

    前田あずさ, 前田あずさ, 西田崇, 青山絵理子, 川木晴美, 久保田聡, 窪木拓男, LYONS Karen M, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   21st   2008

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  • CCN2/CTGFの軟骨特異的過剰発現マウスモデルの作製と解析

    冨田奈緒, 冨田奈緒, 服部高子, 伊藤慎将, 伊藤慎将, 青山絵理子, 青山絵理子, 矢尾真弓, 山城隆, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   21st   2008

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  • マイクロRNA18aによるCcn2/Ctgf遺伝子の制御機構の解明とその軟骨分化における意義

    大河原敏博, 大河原敏博, 久保田聡, 川木晴美, 近藤誠二, 江口傑徳, 佐々木朗, 滝川正春

    生化学   2008

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  • Effect of nicotine on CCN2/CTGF production by the cell from human periodontal tissue

    Takeuchi Hiroko, Murakashi Etsuko, Kubota Satoshi, Takigawa Masaharu, Numabe Yukihiro

    Program and Abstracts of Annual Meeting of the Japanese Society of Periodontology   2008   121 - 121   2008

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    DOI： 10.14833/amjsp.2008s.0.121.0

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  • 結合組織成長因子(CCN2/CTGF)とアグリカンとの結合についての解析(Analysis of binding between CCN2/CTGF and aggrecan)

    青山 絵理子, 服部 高子, 荒木 大介, 星島 光博, 滝川 正春

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   80回・30回   2T22 - 13   2007.11

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  • 軟骨細胞における低密度リポタンパク受容体関連タンパク1(LRP1)の機能解析(Functional analysis of the low density lipoprotein receptor-related protein (LRP1) in chondrocytes)

    河田 かずみ, 久保田 聡, 江口 傑徳, 青山 絵里子, 皆木 省吾, 滝川 正春

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   80回・30回   2T19 - 6   2007.11

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  • 軟骨細胞におけるCCNファミリー2/結合組織成長因子(CCN2/CTGF)のオートクリン発現メカニズムの解明

    西田 崇, 前田 あずさ, 久保田 聡, 滝川 正春

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   80回・30回   4T15 - 10   2007.11

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  • 軟骨特異的にCCN2/CTGFを過剰発現したトランスジェニックマウスの作製と解析

    冨田 奈緒, 服部 高子, 矢尾 真弓, 青山 絵理子, 山城 隆, 滝川 正春

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   80回・30回   2T6 - 2   2007.11

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  • Novel transcription factor-like function of MMP-3/stromelysin-1 that regulates connective tissue growth factor (CTGF/CCN2) gene transcription

    T. Eguchi, S. Kubota, K. Kawata, Y. Mukudai, T. Yanagita, T. Ohgawara, J. Uehara, S. Ibaragi, M. Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   22   S261 - S261   2007.9

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  • CCN2ノックアウトマウスを用いたCCN2およびCCN3の軟骨分化における機能解析

    川木晴美, 久保田聡, 鈴木晶子, 前田健康, 滝川正春

    J Oral Biosci   49 ( Supplement )   98   2007.8

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  • 軟骨特異的CCN2/CTGF過剰発現トランスジェニックマウスの作製とCCN2/CTGFの内軟骨性骨化に及ぼす影響について

    冨田 奈緒, 服部 高子, 青山 絵理子, 山城 隆, 滝川 正春

    Journal of Oral Biosciences   49 ( Suppl. )   125 - 125   2007.8

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  • CCN2ノックアウトマウスを用いた骨芽細胞分化におけるCCNファミリータンパク質の機能解

    川木晴美, 久保田聡, 鈴木晶子, 前田健康, PARBAL Bernardo, LYONS Karen, 滝川正春

    日本骨代謝学会学術集会プログラム抄録集   25th   198   2007.6

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  • 成長板軟骨細胞におけるCCN4/WISP1 mRNAおよびそのスプライシングバリアントの発現とその機能

    柳田 剛志, 久保田 聡, 川木 晴美, 河田 かずみ, 近藤 誠二, 山本 照子, 山城 隆, 田中 真二, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   25回   236 - 236   2007.6

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  • CCN2/CTGF過剰発現トランスジェニックマウスの作製によるCCN2/CTGFの内軟骨性骨化における役割解明

    冨田 奈緒, 服部 高子, 矢尾 真弓, 山城 隆, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   25回   247 - 247   2007.6

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  • 軟骨細胞におけるCCNファミリー2/結合組織成長因子(CCN2/CTGF)によるVEGF遺伝子発現制御機構の解明

    西田 崇, 前田 あずさ, 川木 晴美, 久保田 聡, Lyons Karen, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   25回   182 - 182   2007.6

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  • ウサギ半月板細胞におけるCCNファミリー2/結合組織成長因子(CCN2/CTGF)発現に与えるメカニカルストレスの影響

    前田 あずさ, 西田 崇, 川木 晴美, 久保田 聡, 窪木 拓男, 滝川 正春

    日本骨代謝学会学術集会プログラム抄録集   25回   237 - 237   2007.6

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  • ハイドロキシアパタイトを援用した骨再生におけるCCN2/CTGFの効果

    大島 正充, 大野 充昭, 久保田 聡, 藤澤 拓生, 園山 亘, 秋山 謙太郎, 川木 晴美, 西田 崇, 滝川 正春, 窪木 拓男

    日本骨代謝学会学術集会プログラム抄録集   25回   254 - 254   2007.6

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  • CCN2ノックアウトマウスを用いたCCN3の軟骨分化における機能解析

    川木晴美, 久保田聡, 鈴木晶子, 西田崇, 前田健康, PERBAL Bernard, LYONS Karen M, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   20th   84   2007

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  • CCN2はフィブロネクチン及びマトリリン3と相互作用し,軟骨細胞の接着および細胞外マトリックスの重合を制御している

    星島光博, 服部高子, 荒木大介, 青山絵理子, 滝川正春

    岡山歯学会雑誌   26 ( 1 )   2007

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  • 軟骨細胞において結合組織成長因子/CCNファミリー2(CTGF/CCN2)はHIF-1αの発現を介してVEGF発現を制御する

    西田崇, 久保田聡, 前田あずさ, 前田あずさ, 服部高子, 川木晴美, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   20th   2007

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  • 軟骨成長・分化因子CCN2/CTGFとMatrilin3の相互作用

    荒木大介, 服部高子, 青山絵理子, 星島光博, 滝川正春

    Journal of Oral Biosciences   49 ( Supplement )   2007

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  • 結合組織成長因子(CCN2/CTGF)結合タンパク質の同定および軟骨細胞におけるその結合の生理的意義

    青山絵里子, 荒木大介, 星島光博, 服部高子, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   20th   2007

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  • Tip60によるSox9,Sox5のクロマチンを介した軟骨分化の制御

    服部高子, 滝川正春

    日本骨代謝学会学術集会プログラム抄録集   25th   2007

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  • 結合組織成長因子(CCN2/CTGF)とアグリカンとの結合の生理的意義の解析

    青山絵理子, 服部高子, 荒木大介, 星島光博, 滝川正春

    日本骨代謝学会学術集会プログラム抄録集   25th   2007

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  • 軟骨細胞においてマトリックス金属プロテアーゼ-3(MMP3)は核移行し結合組織成長因子(CCN2/CTGF)の転写活性化因子として働く

    江口傑徳, 久保田聡, 河田かずみ, 椋代義樹, 大河原敏博, 上原淳二, 伊原木聰一郎, 佐々木朗, 窪木拓男, 滝川正春, 滝川正春

    生化学   2007

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  • 軟骨細胞にみられる低密度リポタンパク受容体関連タンパク1(LRP1)の局在と機能の解析

    河田かずみ, 河田かずみ, 久保田聡, 江口傑徳, 青山絵里子, 川木晴美, 岡森彦, 皆木省吾, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   20th   2007

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  • Plasma connective tissue growth factor is a potential marker of diastolic function and myocardial fibrosis in patients with chronic heart failure

    Norimichi Koitabashi, Masashi Arai, Kazuo Niwano, Atai Watanabe, Hiroshi Tada, Takuji Toyama, Hitoshi Adachi, Shigeto Naito, Shigeru Oshima, Takashi Nishicla, Satoshi Kubota, Masaharu Takigawa, Masahiko Kurabayashi

    CIRCULATION   114 ( 18 )   372 - 372   2006.10

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  • Purification and functional characterization of a protein that regulate ccn2 gene expression during chicken chondrocyte differentiation.

    Y. Mukudai, S. Kubota, S. Kondo, T. Eguchi, H. Kawaki, M. Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   21   S149 - S149   2006.9

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  • CCN2ノックアウトマウスを用いた内軟骨性骨化過程におけるCCNファミリーメンバーの役割の解析

    川木晴美, 久保田聡, 鈴木晶子, PERBAL Bernard, 前田健康, LYONS Karen M, 滝川正春

    日本骨代謝学会学術集会プログラム抄録集   24th   168   2006

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  • ラット大腿骨骨欠損におけるCTGF/CCN2 の効果 Reviewed

    菊池剛, 浅海浩二, 三谷茂, 尾崎敏文, 久保田聡, 河田かずみ, 滝川正春, 田畑泰彦

    第24 回日本骨代謝学会学術集会（2006.7.7. 東京）   2006

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  • CCN ファミリータンパク質の内軟骨性骨化制御機構と骨・軟骨再生作用 Reviewed

    久保田聡, 椋代義樹, 菊池剛, 大野充昭, 川木晴美, 柳田剛志, 西田崇, 田畑泰彦, 窪木拓男, 滝川正春

    第24 回日本骨代謝学会シンポジウム 硬組織再生研究の最前線（2006.7.7. 東京）   24th   2006

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  • The gene expressions of connective tissue growth factor and brain natriuretic peptide are coordinately regulated in cardiac myocytes

    N Koitabashi, MAM Morita, S Hara, K Niwano, A Watanabe, M Kurabayashi, N Takashi, S Kubota, M Takigawa

    JOURNAL OF CARDIAC FAILURE   11 ( 9 )   S316 - S316   2005.12

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  • The balance of connective tissue growth factor and brain natriuretic peptide regulates myocardial fibrosis and stiffness

    N Koitabashi, M Arai, M Morita, S Hara, K Niwano, A Watanabe, M Kurabayashi, T Nishida, S Kubota, M Takigawa

    JOURNAL OF CARDIAC FAILURE   11 ( 9 )   S278 - S278   2005.12

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  • Interplay of connective tissue growth factor and brain natriuretic peptide secreted by cardiac myocytes regulates collagen production in cardiac fibroblasts

    N Koitabashi, M Arai, M Morita, S Hara, K Niwano, A Watanabe, M Kurabayashi, S Kubota, T Nishida, M Takigawa

    CIRCULATION   112 ( 17 )   U153 - U153   2005.10

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  • Disproportionate increase of plasma connective tissue growth factor against brain natriuretic peptide is a potential marker of myocardial fibrosis

    N Koitabashi, M Arai, M Morita, S Hara, K Niwano, A Watanabe, M Kurabayashi, S Kubata, T Nishida, M Takigawa

    CIRCULATION   112 ( 17 )   U787 - U787   2005.10

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  • Connective tissue growth factor (CTGF/CCN2) enhanced human bone marrow stromall cell attachment in vitro and migration and survival of the cells in a hydroxyapatite scaffold in vivo.

    M Ono, W Sonoyama, K Akiyama, T Fujisawa, T Nishida, M Takigawa, T Kuboki

    JOURNAL OF BONE AND MINERAL RESEARCH   20 ( 9 )   S203 - S204   2005.9

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  • Connective tissue growth factor (CTGF/CCN2) reinforces the molecular phenotype of aauricular chondrocytes in vitro.

    T Fujisawa, K Nakao, T Hattori, S Kubota, T Kuboki, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   20 ( 9 )   S197 - S197   2005.9

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  • Post-transcriptional regulation of CCN2/CTGF gene expression during differentiation of chicken chondrocytes: involvement of a putative trans-factor which interacts with a cis-element in the 3 '-UTR of mRNA

    Y Mukudai, S Kubota, T Eguchi, S Kondo, K Nakao, M Takigawa

    FEBS JOURNAL   272   284 - 285   2005.7

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  • Connective tissue growth factor mediates the profibrotic effects of transforming growth factor-β produced by tubular epithelial cells in response to high glucose

    KOBAYASHI Tatsuya, INOUE Tsutomu, OKADA Hirokazu, KIKUTA Tomohiro, KANNO Yoshihiko, NISHIDA Takashi, TAKIGAWA Masaharu, SUGAYA Takeshi, SUZUKI Hiromichi

    Clin Exp Nephrol   9 ( 2 )   114 - 121   2005.6

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  • Expression of CTGF/Hcs 24 during fracture healing and distraction osteogenesis

    KIKUCHI Takeshi

    16   134 - 134   2005.5

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  • Cardiac Myocytes Regulates Collagen Production Through Connective Tissue Growth Factor Secretion Induced by Various Neurohumoral Factors(Molecular Biology, Myocardium 1 (M), The 69th Annual Scientific Meeting of the Japanese Circulation Society)

    Koitabashi Norimichi, Arai Masashi, Hara Shiro, Niwano Kazuo, Watanabe Atai, Kurabayashi Masahiko, Nishida Takashi, Takigawa Masaharu

    Circulation journal : official journal of the Japanese Circulation Society   69   142 - 142   2005.3

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  • CCN proteins: A new family of cell growth and differentiation regulators

    Bernard Perbal, Masaharu Takigawa

    CCN Proteins: A New Family of Cell Growth and Differentiation Regulators   1 - 311   2005.1

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    DOI： 10.1142/P384

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  • デキサメタゾン刺激はCCN2/CTGFの誘導を介して軟骨細胞のリウマチ関連抗原HSP47/RA-A47の発現量を減少させる リウマチ病態および軟骨組織の修復との関連性について

    矢尾真弓, 矢尾真弓, 服部高子, 川木晴美, 久保田聡, 油谷安孝, 佐々木朗, 滝川正春

    Journal of Oral Biosciences   47 ( Supplement )   2005

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  • 転写因子SOX9,p53の活性制御機構-SUMO化との関連は?

    安田秀世, 巻さゆみ, 滝川正春, 服部高子

    日本分子生物学会年会講演要旨集   28th   2005

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  • 関節炎と軟骨(2)4 変形性関節症においても,2型腫よう壊死因子可溶性受容体は関節破壊や炎症を調節する

    上原淳二, 藤沢拓生, 大野充昭, 前川賢治, 服部高子, 滝川正春, 窪木拓男

    日本軟骨代謝学会プログラム・抄録集   18th   2005

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  • CCN2/CTGFはコラーゲン特異的分子シャペロンHSP47/リウマチ関連抗原RA-A47の発現量を減少させる-リウマチ病態および軟骨組織の修復との関連-

    矢尾真弓, 矢尾真弓, 服部高子, 川木晴美, 油谷安孝, 滝川正春

    日本骨代謝学会学術集会プログラム抄録集   23rd   2005

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  • 転写活性化因子Tip60のSox9,Sox5複合体への会合を介した軟骨分化の制御

    服部高子, 服部高子, 安田秀世, 滝川正春, DE CROMBRUGGHE Benoit

    日本分子生物学会年会講演要旨集   28th   2005

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  • 関節炎と軟骨(1)2 コラーゲン特異的分子シャペロンHSP47/RA-A47の発現量低下が軟骨細胞の破壊とHSP47/RA-A47の細胞表面への露出を引き起こす:関節リウマチにおける自己抗原としての認識機構

    服部高子, VON DER MARK Klaus, 川木晴美, 油谷安孝, 久保田聡, 中西徹, DE CROMBRUGGHE Benoit, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   18th   2005

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  • 成長因子 1 二次骨化中心形成過程におけるCTGF/CCN2およびMMP-9の発現と局在

    岡森彦, 久保田聡, 近藤誠二, 江口傑徳, 河田かずみ, 黒田知沙, 皆木省吾, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   18th   2005

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  • 軟骨発生と分化 6 軟骨細胞における低密度リポタンパク受容体関連タンパク1(LRP1)の発現

    河田かずみ, 江口傑徳, 久保田聡, 川木晴美, 岡森彦, 皆木省吾, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   18th   2005

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  • 関節炎と軟骨(2)2 変形性関節症(OA)モデルにおけるM-CSFの産生と修復における意義

    中尾匡志, 久保田聡, 西田崇, 岡森彦, 江口傑徳, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   18th   2005

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  • 軟骨細胞の分化過程におけるCCN2/CTGF遺伝子転写後調節機構の解析

    椋代 義樹, 久保田 聡, 江口 傑徳, 近藤 誠二, 中尾 匡志, 滝川 正春

    Journal of oral biosciences   46 ( 5 )   396 - 396   2004.9

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  • 軟骨細胞におけるM-CSFとCTGFの協調的誘導とその効果

    中尾 匡志, 久保田 聡, 西田 崇, 江口 傑徳, 滝川 正春

    Journal of oral biosciences   46 ( 5 )   396 - 396   2004.9

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  • CTGF,ErbB受容体遺伝子発現の、Cbfal遺伝子ノックアウトによる影響

    山合 友一朗, 中西 徹, 井上 美穂, 杉本 朋貞, 滝川 正春

    Journal of oral biosciences   46 ( 5 )   467 - 467   2004.9

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  • 唾液腺原発多形性腺腫におけるCTGFの発現は、軟骨様成分の形成に関与するか?

    草深 公秀, 滝川 正春, 西田 崇, 北川 雅恵, 工藤 保誠, 小川 郁子, 高田 隆, 草深 美智

    Journal of oral biosciences   46 ( 5 )   400 - 400   2004.9

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  • Development of the Dentin Regeneration Therapy : Analysis of expression of osteonectin in human dental pulp cells by CTGF stimulation

    TAKAGI Ryo, SHIMIZU Hirotoshi, NISHITANI Yoshihiro, YAMADA Tomiko, TAKAHASHI Kazuhiro, NISHIDA Takashi, TAKIGAWA Masaharu, YAMAUCHI Junichi, YOSHIYAMA Masahiro

    47   90 - 90   2004.5

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  • ラット骨延長モデルにおける神経栄養因子とその受容体の発現

    相賀 礼子, 浅海 浩二, 門田 弘明, 三谷 茂, 西田圭一郎, 井上 一, 中西 徹, 滝川 正春

    日本創外固定・骨延長学会雑誌   2004

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  • 軟骨特異的転写因子Sox9のSUMO化による活性調節

    服部高子, 西田有, 華表友暁, 滝川正春, DE CROMBRUGGHE B, 安田秀世

    日本分子生物学会年会プログラム・講演要旨集   27th   2004

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  • 関節軟骨細胞の修復と維持にM-CSFとCTGFの協調的誘導が関与する

    中尾匡志, 久保田聡, 縄稚久美子, 西田崇, 中西徹, 井上美穂, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   17th   2004

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  • コラーゲン特異的分子シャペロンRA-A47/HSP47:関節リウマチにおける自己抗原としての認識機構

    服部高子, 川木晴美, 油谷安孝, 久保田聡, 中西徹, 滝川正春

    日本骨代謝学会学術集会プログラム抄録集   22nd   2004

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  • 軟骨細胞における関節リウマチ関連抗原RA-A47の発現抑制による軟骨破壊因子の誘導とRA-A47自身の細胞表面への露出

    服部高子, 久保田聡, 油谷安孝, 中西徹, 滝川正春

    日本リウマチ学会総会・学術集会抄録集   48th   2004

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  • 癌抑制遺伝子産物p53のSUMO化の意義

    服部高子, 西田有, 華表友暁, 滝川正春, 巻さゆみ, 上野憲道, DECROMBRUGGHE B, 安田秀世

    日本分子生物学会年会プログラム・講演要旨集   27th   2004

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  • 軟骨細胞の分化過程におけるニワトリ結合組織成長因子(CTGF/Hcs24)遺伝子の転写後発現調節機構の解析

    椋代義樹, 久保田聡, 江口傑徳, 近藤誠二, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   17th   2004

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  • Connective Tissue Growth Factor (CTGF/CCN2)プロモーター上の3つのシスエレメント〈軟骨細胞優位型エンハンサー(TRENDIC),スマッド結合配列(SBE),TGF-beta応答領域(TbRE)〉の機能比較-軟骨細胞様細胞株HCS-2/8と乳癌細胞株MDA231における違い-

    江口傑徳, 久保田聡, 河田かずみ, 中尾匡志, 大河原敏博, 滝川正春

    日本分子生物学会年会プログラム・講演要旨集   27th   2004

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  • stromelysin-1の翻訳開始機構に関する検討-軟骨細胞様細胞株HCS-2/8を用いた解析-

    柳田剛志, 江口傑徳, 久保田聡, 山本照子, 滝川正春

    日本分子生物学会年会プログラム・講演要旨集   27th   2004

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  • Immunolocalization and gene expression of CTGF in rat mandibular condylar cartilage

    T Fukunaga, T Yamashiro, TA Balam, N Kobashi, M Takigawa, T Takano-Yamamoto

    JOURNAL OF DENTAL RESEARCH   82   408 - 408   2003.12

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  • ヒト歯髄由来間葉系幹細胞の細胞接着ならびに増殖に対する各種成長因子の影響

    園山 亘, 藤沢 拓生, 大野 充昭, 志茂 剛, 西田 崇, 滝川 正春, 窪木 拓男

    日本再生歯科医学会誌   1 ( 1 )   77 - 77   2003.12

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  • Blockade of connective tissue growth factor ameliorates renal tubuolointerstitial fibrosis.

    H Yokoi, M Mukoyama, T Nagae, K Mori, T Suganami, K Sawai, T Yoshioka, M Koshikawa, T Nishida, M Takigawa, A Sugawara, K Nakao

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   14   374A - 374A   2003.11

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  • ErbB2のノックアウトマウスにおける肥大軟骨のアポトーシス

    山合 友一朗, 中西 徹., 縄稚 久美子, 井上 美穂, 杉本 朋貞, 滝川 正春.

    歯科基礎医学会雑誌   45 ( 5 )   320 - 320   2003.9

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  • 軟骨細胞におけるm-csfr/c-fmsの発現と意義

    中尾 匡志, 久保田 聡, 縄稚 久美子, 岡 森彦, 西田 崇, 中西 徹, 井上 美穗, 滝川 正春

    歯科基礎医学会雑誌   45 ( 5 )   279 - 279   2003.9

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  • モジュール特異的抗体による結合組織成長因子CTGF/Hcs24の構造と機能の解析

    湊 雅直., 久保田 聡, 川木 晴美, 西田 崇, 中西 徹, 山本 照子, 滝川 正春

    歯科基礎医学会雑誌   45 ( 5 )   303 - 303   2003.9

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  • Induction of connective tissue growth factor hypertrophic chondrocyte-specific 24 CCN2 gene by dexamethasone in human chondrocytic cells: Mechanism and biological outcome.

    S Kubota, NH Moritani, H Kawaki, H Mimura, M Minato, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   18   S301 - S301   2003.9

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  • Transcriptional induction of the gene encoding alpha 3 chain of type IX collagen (COL9A3) by SOX9 contributes to the susceptibility of knee osteoarthritis.

    T Ikeda, A Mabuchi, A Fukuda, S Kamekura, Kou, I, H Hiraoka, A Kawakami, S Yamamoto, U Chung, Y Takatori, M Takigawa, H Sakai, A Sudo, A Uchida, K Nakamura, H Kawaguchi, S Ikegaw

    JOURNAL OF BONE AND MINERAL RESEARCH   18   S69 - S69   2003.9

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  • Tyrosine kinase-type receptors erbB4 and m-csfr/c-fms gene expression in chondrocytes.

    K. Nawachi, S. Kubota, M. Inoue, T. Nishida, T. Kuboki, T. Nakanishi, H. Yatani, M. Takigawa

    JOURNAL OF DENTAL RESEARCH   82   B357 - B357   2003.6

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  • The effect of the 5 ' end of the open reading frame of CEF-10/CYR61 MRNA as a CIS element of gene expression

    Y Mukudai, S Kubota, M Takigawa

    BONE   32 ( 5 )   S131 - S131   2003.5

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  • Regeneration of defects in the articular cartilage in rat knee joints by connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24)

    T Nishida, S Kubota, S Kojima, T Kuboki, T Kushibiki, Y Tabata, M Takigawa

    BONE   32 ( 5 )   S101 - S101   2003.5

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  • Coordinated gene induction and repression of two CCN family members, CTGF and Cyr61, in chondrocytic cells

    NH Moritani, S Kubota, K Nakao, T Sugahara, M Takigawa

    BONE   32 ( 5 )   S98 - S98   2003.5

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  • Analysis of gene expression profiles and differentiation patterns of human mesenchymal stem cell (HMSC) clones

    T Nakanishi, K Ohyama, T Yamaai, M Takigawa

    BONE   32 ( 5 )   S136 - S136   2003.5

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  • Expression of CTGF/Hcs24 (connective tissue growth factor) in a model of rat distraction osteogenesis

    14   198 - 198   2003.3

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  • 歯髄細胞再生の最前線:歯髄幹細胞(DPSC)の役割.

    中西 徹, 大山和美, 滝川正春

    ザ・クインテッセンス   22,220-221   2003

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  • 象牙質再生療法の開発--CTGF刺激によるヒト歯髄細胞におけるオステオネクチンの発現の解析--.

    清水洋利, 西谷佳浩, 山田登美子, 西田 崇, 滝川正春, 吉山昌宏

    日本再生歯科医学会誌   2003

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  • 成長因子(CTGF)を応用した象牙質再生療法開発の可能性を探る.

    清水洋利, 西谷佳浩, 山田登美子, 高橋和宏, 西田 崇, 滝川正春, 吉山昌宏

    ザ・クインテッセンス   22,222-223   2003

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  • 軟骨細胞の分化課程におけるニワトリ結合組織成長因子(CTGF/Hcs24)遺伝子の転写後発現調節機構の解析

    椋代義樹, 久保田聡, 江口傑徳, 近藤誠二, 滝川正春

    日本分子生物学会年会プログラム・講演要旨集   26th   2003

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  • Development of The Dentin Regeneration Therapy-Expression of Type1 collagen and ALP induced by CTGF in human cultured dental pulp-

    Hirotoshi Shimizu, Yoshihiro Nishitani, Tomiko Yamada, Takashi Nishida, Masaharu Takigawa, Masahiro Yoshiyama, Dept of Operative Dentistry Okayama Univ. Graduate School of Medicine and Dentistry, Dept of Operative Dentistry Okayama Univ. Graduate School of Medicine and Dentistry, Dept of Operative Dentistry Okayama Univ. Graduate School of Medicine and Dentistry, Dept of Biochemistry Okayama Univ. Graduate School of Medicine and Dentistry, Dept of Biochemistry Okayama Univ. Graduate School of Medicine and Dentistry, Dept of Operative Dentistry Okayama Univ. Graduate School of Medicine and Dentistry

    Journal of hard tissue biology = Journal of hard tissue biology   11 ( 2 )   76 - 76   2002.12

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  • Hepatocyte growth factor counteracts transforming growth factor-beta(1), through attenuation of connective tissue growth factor induction, and prevents renal fibrogenesis in 5/6 nephrectomized mice

    T Inoue, H Okada, T Kobayashi, Y Watanabe, Y Kanno, JB Kopp, T Nishida, M Takigawa, M Ueno, T Nakamura, H Suzuki

    FASEB JOURNAL   16 ( 14 )   268 - +   2002.12

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  • ヒト口腔扁平上皮癌細胞株における結合組織成長因子(CTGF)の腫瘍細胞増殖抑制効果

    森谷 徳文, 久保田 聡, 近藤 誠二, 西田 崇, 川木 晴美, 菅原 利夫, 滝川 正春

    歯科基礎医学会雑誌   44 ( 5 )   395 - 395   2002.9

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  • 肥大軟骨細胞特異的遺伝子産物CTGF/Hcs24のモジュール特異的抗体の解析とその軟骨細胞分化促進効果

    湊 雅直, 久保田 聡, 川木 晴美, 西田 崇, 中西 徹, 山本 照子, 滝川 正春

    歯科基礎医学会雑誌   44 ( 5 )   388 - 388   2002.9

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  • 硬組織発生過程でのerbB4遺伝子発現

    山合 友一朗, 中西 徹, 縄稚 久美子, 井上 美穂, 杉本 朋貞, 滝川 正春

    歯科基礎医学会雑誌   44 ( 5 )   435 - 435   2002.9

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  • 結合組織成長因子CTGF/Hcs24遺伝子の軟骨由来細胞におけるグルココルチコイドによる発現誘導

    久保田 聡, 森谷 徳文, 三村 晴世, 川木 晴美, 湊 雅直, 滝川 正春

    歯科基礎医学会雑誌   44 ( 5 )   437 - 437   2002.9

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  • チロシンキナーゼ型レセプターErbB4遺伝子の軟骨細胞における発現

    縄稚 久美子, 久保田 聡, 西田 崇, 吉道玄, 中西 徹, 完山 学, 窪木 拓男, 矢谷 博文, 山合 友一郎, 滝川 正春

    歯科基礎医学会雑誌   44 ( 5 )   388 - 388   2002.9

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  • DNAマイクロアレイによる間葉系幹細胞の発現プロファイリング

    中西 徹, 大山 和美, 滝川 正春

    歯科基礎医学会雑誌   44 ( 5 )   389 - 389   2002.9

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  • Novel cis-element TRENDIC that enhance connective tissue growth factor (ctgf) gene expression in chondrocytic HCS-2/8.

    T Eguchi, S Kubota, S Kondo, Y Mukudai, T Kuboki, H Yatani, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   17   S224 - S224   2002.9

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  • Analysis of gene expression in osteoblastic cell stimulated by connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24).

    E Nakata, T Nakanishi, T Nishida, A Kawai, H Doi, H Inoue, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   17   S224 - S224   2002.9

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  • Effects of IL-1beta and LPS on CTGF expression in mouse-derived odontoblast-like cells, MDPC-23.

    W Sonoyama, T Kuboki, T Fujisawa, T Eguchi, J Uehara, H Yatani, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   17   S327 - S327   2002.9

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  • CTGF/Hcs24, a hypertrophic chondrocyte-specific gene product, stimulates proliferation and differentiation but not hypertrophy of cultured articular chondrocytes.

    T Nishida, S Kubota, T Nakanishi, T Kuboki, G Yosimichi, S Kondo, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   17   S180 - S181   2002.9

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  • Role of connective tissue growth factor and its intracellular signaling in podocytes.

    M Koshikawa, K Mori, M Mukoyama, A Sugawara, T Suganami, K Sawai, H Yokoi, N Kobayashi, M Takigawa, P Mundel, K Nakao

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   13   314A - 314A   2002.9

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  • Hepatocyte growth factor counteracts transforming growth factor-betal via attenuation of connective tissue growth factor induction and prevents renal fibrogenesis in 5/6 nephrectomized mice.

    T Inoue, H Okada, Y Kanno, T Kobayashi, Y Watanabe, K Kikuta, JB Kopp, M Takigawa, T Nakamura, H Suzuki

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   13   746A - 747A   2002.9

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  • CTGF/Hcs24 induces chondrocyte differentiation through p38 mitogen-activated protein kinase (p38MAPK), and proliferation through p44/42 MAPK/extracellular-signal regulated kinase (ERK).

    G Yosimichi, T Nakanishi, T Nishida, T Hattori, T Takano-Yamamoto, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   17   S222 - S223   2002.9

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  • Kunitz-type protease inhibitor bikunin disrupts phorbol ester-induced oligomerization of CD44 variant isoforms containing epitope v9 and subsequently suppresses expression of urokinase-type plasminogen activator in human chondrosarcoma cells. (vol 277, pg 8022, 2002)

    M Suzuki, H Kobayashi, M Fujie, T Nishida, M Takigawa, N Kanayama, T Terao

    JOURNAL OF BIOLOGICAL CHEMISTRY   277 ( 18 )   16346 - 16346   2002.5

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  • REGULATION OF BIGLYCAN AND DECORIN SYNTHESIS BY CONNECTIVE TISSUE GROWTH FACTOR IN CULTURED BOVINE AORTIC ENDOTHELIAL CELLS

    Yamamoto Chika, Oh-i Mami, Fujiwara Yasuyuki, Kaji Toshiyuki, Nishida Takashi, Nakanishi Tohru, Takigawa Masaharu, Kinsella Michael G., Wight Thomas N.

    Connective tissue   34 ( 1 )   50 - 50   2002.4

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    Connective tissue growth factor (CTGF) is a regulator of vascular endothelial cell functions but little is know about the regulation of proteoglycan synthesis by the growth factor. Since endothelial cell proteoglycan synthesis is often regulated depending on the cell density, dense and sparse cultures of bovine aortic endothelial cells were metabolically labeled with [^<35>S]sulfate or ^<35>S-labaled amino acids in the presence of recombinant human CTGF. The labeled proteoglycans were characterized by DEAE-Sephacel ion exchange chromatography and Sepharose CL-4B molecular sieve chromatography. The glycosaminoglycan (GAGs) M_r and composition were analyzed by Sepharose CL-6B chromatography, and the core protein M_r was analyzed by SDS-polyacrylamide gel electrophoresis, before and after digestion with papain, heparitinase or chondroitin ABC lyase. The core proteins were identified by Western blot analysis and core protein mRNAs were determined by quantitative RT-PCR. The results indicated that CTGF suppresses the synthesis of biglycan but newly induces that of decorin in endothelial cells when the cell density is low. However, neither the hydrodynamic size nor the GAG chain length of these two small chondroitin/dermatan sulfate proteoglycans was changed by the growth factor. The present data suggest that CTGF is a regulator of the synthesis of small chondroitin/dermatan sulfate proteoglycans, biglycan in vascular endothelial cells depending on the cell density.

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  • Effects of proinflammatory factors on CTGF expression in odontoblast-like cells

    W Sonoyama, T Kuboki, T Fujisawa, T Eguchi, J Uehara, S Takashiba, H Yatani, M Takigawa

    JOURNAL OF DENTAL RESEARCH   81   A155 - A155   2002.3

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  • Expression of CTGF in endochondral and intramembranous ossification during mandibular fracture healing

    T Fukunaga, T Yamashiro, K Yamashita, JN Pereira, M Takigawa, T Takano-Yamamoto

    JOURNAL OF DENTAL RESEARCH   81   A190 - A190   2002.3

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  • CTGF upregulation observed in the rat tooth extraction sockets.

    M Kanyama, T Kuboki, K Akiyama, F Miyauchi, K Nawachi, H Yatani, S Kubota, T Nakanishi, M Takigawa

    JOURNAL OF DENTAL RESEARCH   81   A107 - A107   2002.3

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  • 骨軟骨組織修復における結合組織成長因子CTGF/Ecogeninの役割．

    西田 崇, 小島俊司, 久保田聡, 窪木拓男, 田畑泰彦, 櫛引俊宏, 中西 徹, 滝川正春

    第４回大阪組織工学研究セミナー．   2002

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  • Promoter activity determinant of human connective tissue growth factor (CTGF/Hcs24) gene in a human chondrocytic cell line, HCS-2/8.

    T Eguchi, S Kubota, S Kondo, T Shimo, T Nakanishi, T Kuboki, H Yatani, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   16   S326 - S326   2001.9

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  • 低酸素によるヒト乳癌細胞における結合組織成長因子CTGF及びマトリクスメタロプロテアーゼの発現誘導

    近藤 誠二, 久保田 聡, 志茂 剛, 西田 崇, 吉道 玄, 江口 傑徳, 菅原 利夫, 滝川 正春

    日本癌学会総会記事   60回   183 - 183   2001.9

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  • Expression of connective tissue growth factor/hypertrophic chrondrocyte-specific gene product 24 (CTGF/Hcs24) during fracture healing.

    E Nakata, T Nakanishi, A Kawai, K Asaumi, T Nishida, H Inoue, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   16   S326 - S326   2001.9

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  • 軟骨由来成長因子CTGF/Hcs24遺伝子の転写後制御エレメントCAESARの構造と機能

    久保田 聡, 近藤 誠二, 江口 傑徳, 服部 高子, 中西 徹, 滝川 正春

    歯科基礎医学会雑誌   43 ( 5 )   554 - 554   2001.8

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  • マウス下顎頭軟骨におけるCbfa1遺伝子の発現

    秋山 謙太郎, 窪木 拓男, 完山 学, 縄稚 久美子, 矢谷 博文, 山下 和夫, 山本 照子, 中西 徹, 滝川 正春

    歯科基礎医学会雑誌   43 ( 5 )   583 - 583   2001.8

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  • 軟骨由来成長因子CTGFトランスジェニックマウスの硬組織形成と遺伝子発現の解析

    山合 友一朗, 中西 徹, 縄雅 久美子, 吉道 玄, 浅野 将宏, 杉本 朋貞, 滝川 正春

    歯科基礎医学会雑誌   43 ( 5 )   573 - 573   2001.8

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  • 軟骨様細胞株HCS-2/8における多機能成長因子CTGF/Hcs24の転写から分泌まで

    江口 傑徳, 久保田 聡, 志茂 剛, 近藤 誠二, 中西 徹, 矢谷 博文, 滝川 正春

    生化学   73 ( 8 )   778 - 778   2001.8

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  • 低酸素による結合組織成長因子(CTGF)及びマトリクスメタロプロテアーゼ(MMP)活性の協調的発現誘導

    近藤 誠二, 久保田 聡, 志茂 剛, 西田 崇, 吉道 玄, 江口 傑徳, 菅原 利夫, 滝川 正春

    歯科基礎医学会雑誌   43 ( 5 )   632 - 632   2001.8

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  • ヒト軟骨様細胞株HCS-2/8におけるCTGF/Hcs24遺伝子のプロモーター活性決定因子

    江口 傑徳, 久保田 聡, 近藤 誠二, 志茂 剛, 中西 徹, 窪木 拓男, 矢谷 博文, 滝川 正春

    歯科基礎医学会雑誌   43 ( 5 )   557 - 557   2001.8

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  • 軟骨由来成長因子CTGF/Hcs24のヒト軟骨細胞株HCS-2/8におけるプロセシングと分泌の様態

    久保田 聡, 江口 傑徳, 志茂 剛, 西田 崇, 服部 高子, 近藤 誠二, 中西 徹, 滝川 正春

    日本骨代謝学会雑誌   19 ( 2 )   104 - 104   2001.7

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  • 結合組織成長因子(CTGF)は破骨細胞形成に関与する

    吉岡 徳枝, 佐々木 朗, 中西 徹, 志茂 剛, 横山 尚史, 松村 智弘, 滝川 正春

    日本骨代謝学会雑誌   19 ( 2 )   47 - 47   2001.7

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  • ヒト軟骨肉腫由来軟骨様細胞株HCS-2/8における結合組織成長因子CTGF/Hcs24遺伝子のプロモーター活性決定因子

    江口 傑徳, 久保田 聡, 近藤 誠二, 志茂 剛, 中西 徹, 窪木 拓男, 矢谷 博文, 滝川 正春

    日本骨代謝学会雑誌   19 ( 2 )   102 - 102   2001.7

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  • MATRICRINE AND MMPs

    KUBOTA Satoshi, TAKIGAWA Masaharu

    Connective tissue   33 ( 2 )   71 - 71   2001.6

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  • 結合組織成長因子CTGF/Hcs24の軟骨細胞様細胞株HCS-2/8での発現と動態制御

    久保田 聡, 江口 傑徳, 志茂 剛, 服部 高子, 近藤 誠二, 中西 徹, 滝川 正春

    Connective Tissue   33 ( 2 )   157 - 157   2001.6

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  • 骨形成(骨吸収)因子 肥大軟骨細胞由来の成長因子CTGF/Hcs24の骨芽細胞の増殖と分化に与える影響

    滝川 正春, 西田 崇, 中西 徹, 浅野 将宏, 志茂 剛

    厚生労働省特定疾患対策研究事業研究報告書 脊柱靭帯骨化症に関する調査研究班   平成12年度   54 - 60   2001.3

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  • 結合組織成長因子（CTGF/Hcs24）を応用した関節軟骨再生療法の可能性の検討－in vitroおよびin vivoにおける検討－

    西田 崇, 小島俊司, 窪木拓男, 中西 徹, 久保田聡, 滝川正春

    第３回生体組織工学シンポジウム   2001

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  • Cationic polymer-mediated genetic transduction into cultured human chondrocytes

    Ohashi S, Kubo T, Ikeda T, Arai Y, Takahashi K, Hirasawa Y, Takigawa M, Satoh E, Imanishi J, Mazda O

    J Ortho Sci   6 ( 1 )   75 - 81   2001

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  • 軟骨由来の成長因子(Connective Tissue Growth Factor,CTGF/Hcs24)の軟骨細胞増殖,分化促進作用における情報伝達機構の解析

    吉道玄, 中西徹, 西田崇, 服部高子, 山本照子, 滝川正春

    日本骨代謝学会雑誌   19 ( 2 )   2001

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  • Characterization of a Mouse ctgf3′-UTR Segment that Mediates Repressive Regulation of Gene Expression.

    近藤誠二, 久保田聡, 江口傑徳, 服部高子, 中西徹, 菅原利夫, 滝川正春

    日本口腔科学会雑誌   50 ( 6 )   2001

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  • Molecular cloning and characterization of RA-A47, a rheumatoid arthritis-related antigen from a human chondrocytic cell line, HCS-2/8.

    T Hattori, S Kubota, Y Yutani, T Fujisawa, T Nakanishi, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   15   S470 - S470   2000.9

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  • A novel RNA element that confers post-transcriptional repression of human connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) gene.

    S Kubota, S Kondo, T Eguchi, T Hattori, T Nakanishi, RJ Pomerantz, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   15   S340 - S340   2000.9

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  • 軟骨由来成長因子CTGFと転写制御因子Cbfa1の発生過程での遺伝子発現のパターン解析

    山合 友一朗, 中西 徹, 浅野 将宏, 縄稚 久美子, 服部 高子, 杉本 朋貞, 滝川 正春

    歯科基礎医学会雑誌   42 ( 5 )   451 - 451   2000.8

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  • Expression of Connective Tissue Growth Factor (CTGF/Hcs24) in Angiogenesis with Rheumatoid Arthritis

    SHIBAHARA M

    日本整形外科學會雜誌   74 ( 8 )   S1477   2000.8

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  • The Effect of HSP70 Gene Transduction to Chondrocyte

    ARAI Y

    日本整形外科學會雜誌   74 ( 8 )   S1690   2000.8

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  • Roles of CTGF/Hcs24 in the Occurrence and Development of Ossification of the Posterior Longitudinal Ligament of the Spine

    YAMAMOTO Y.

    74 ( 8 )   S1364   2000.8

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  • Localization of Neurotrophins and Their Receptors during Chondro-osteophyte Formation of Osteoarthrosis

    ASAUMI K.

    74 ( 8 )   S1770   2000.8

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  • 肥大軟骨由来の成長因子CTGF/Hcs24による細胞外基質構成タンパク質及び細胞外基質分解酵素発現の制御

    西田 崇, 中西 徹, 志茂 剛, 吉道 玄, 滝川 正春

    日本骨代謝学会雑誌   18 ( 2 )   1 - 1   2000.6

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  • 結合組織成長因子/肥大軟骨細胞特異的遺伝子産物(CTGF/Hcs24)発現による細胞周期変調効果

    久保田 聡, 服部 高子, 志茂 剛, 中西 徹, 滝川 正春

    Connective Tissue   32 ( 2 )   217 - 217   2000.5

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  • Roles of Hcs24/CTGF in the occurence and development of ossification of posterior longitudinal ligament

    YAMAMOTO Y.

    11 ( 1 )   77 - 77   2000.4

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  • Expression of Connective Tissue Growth Factor (CTGF) and Prognosis in Soft Tissue Sarcoma

    SHAKUNAGA T.

    74 ( 2 )   S462   2000.2

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  • 岡山大学歯学部における問題発見解決型教育法（チュートリアル教育）導入の試み

    窪木拓男, 滝川正春

    岡山歯学会誌   19 ( 2 )   295 - 304   2000

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  • ヒト軟骨細胞様培養細胞株HCS-2/8における結合組織成長因子ctgf/ecogenin遺伝子発現制御機構

    江口傑徳, 久保田聡, 近藤誠二, 服部高子, 中西徹, 窪木拓男, 矢谷博文, 滝川正春

    日本分子生物学会年会プログラム・講演要旨集   23rd   2000

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  • 慢性関節リウマチ関連抗原RA-A47の発現量減少による軟骨細胞破壊とアポトーシスの誘導

    服部高子, 久保田聡, 中西徹, 油谷安孝, 滝川正春

    日本分子生物学会年会プログラム・講演要旨集   23rd   2000

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  • 軟骨由来成長因子CTGF/Hcs24遺伝子の転写後調節エレメントCAESAR 変異体分析によって得られた新たな知見

    久保田聡, 近藤誠二, 江口傑徳, 服部高子, 中西徹, 滝川正春

    日本分子生物学会年会プログラム・講演要旨集   23rd   2000

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  • 慢性関節リウマチ関連抗原RA-A47の発現量減少による軟骨細胞障害作用

    服部高子, 川木晴美, 油谷安孝, 久保田聡, 中西徹, 滝川正春

    生化学   72 ( 8 )   2000

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  • 慢性関節リウマチ関連抗原RA-A47の発現レベルの低下にともなう細胞膜への局在変化とRA-A47の自己抗原としての認識機構

    服部高子, 油谷安孝, 藤沢拓生, 中西徹, 滝川正春

    日本骨代謝学会雑誌   18 ( 2 )   2000

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  • 軟骨由来成長因子CTGF/Hcs24による軟骨分化マーカーII型コラーゲンおよびX型コラーゲンの発現促進に対するMAPキナーゼ経路阻害剤の効果

    吉道玄, 中西徹, 服部高子, 西田崇, 山本照子, 滝川正春

    日本骨代謝学会雑誌   18 ( 2 )   2000

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  • 慢性関節リウマチ患者における軟骨細胞分泌タンパク(YKL‐39)に対する抗体の検出

    関根太一, 増子佳世, 松井利浩, 浅原弘嗣, 滝川正春, 西岡久寿樹, 加藤智啓

    日本免疫学会総会・学術集会記録   29   195   1999.10

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  • A cis-acting repressive element in the 3 '-untranslated region of the CTGF gene.

    S Kubota, T Hattori, T Eguchi, S Kondo, T Nakanishi, M Takigawa

    JOURNAL OF BONE AND MINERAL RESEARCH   14   S436 - S436   1999.9

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  • A novel arthritis model mice by scretory protein of articular chondrocytes, YKL-39.

    M Sakata, K Masuko-Hongo, J Tsuruha, H Nakamura, T Sekine, S Yoshino, M Takigawa, T Kato, K Nishioka

    ARTHRITIS AND RHEUMATISM   42 ( 9 )   S257 - S257   1999.9

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  • Agument of articular immune responses to gp-39 and YKL-39 in patients with osteoarthritis.

    J Tsuruha, K Masuko-Hongo, M Sakata, H Nakamura, T Sekine, S Yoshino, M Takigawa, T Kato, K Nishioka

    ARTHRITIS AND RHEUMATISM   42 ( 9 )   S257 - S257   1999.9

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  • 軟骨細胞に対する Cationic Polymer-DNA 複合体を用いた遺伝子導入法の検討

    大橋 鈴世, 久保 俊一, 松田 修, 池田 巧, 新井 祐志, 佐藤 悦子, 滝川 正春, 今西 二郎, 平澤 泰介

    日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association   73 ( 8 )   S1608   1999.8

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  • 骨折治癒過程における軟骨由来成長因子Hcs24/CTGFの発現 : IN VIVO STUDY

    浅海 浩二, 中西 徹, 浅野 将宏, 西田 崇, 川井 章, 三谷 茂, 浅原 弘嗣, 井上 一, 滝川 正春

    日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association   73 ( 8 )   S1781   1999.8

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  • 軟骨由来成長因子CTGF/Hcs24のマウス発生過程での遺伝子発現のパターン解析

    山合 友一朗, 浅野 将宏, 中西 徹, 西田 崇, 吉道 玄, 服部 高子, 杉本 朋貞, 滝川 正春

    歯科基礎医学会雑誌   41 ( 5 )   464 - 464   1999.8

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  • 軟骨由来の成長因子CTGF/Hcs24の歯根膜由来線維芽細胞に対する増殖,成長促進作用

    浅野 将宏, 西田 崇一, 中西 徹, 坪井 佳子, 吉道 玄, 山本 照子, 滝川 正春

    歯科基礎医学会雑誌   41 ( 5 )   448 - 448   1999.8

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  • 慢性関節リウマチにおけるRA-A47の細胞内局在変化と抗原提示

    服部 高子, 藤沢 拓生, 中西 徹, 久保田 聡, 滝川 正春

    歯科基礎医学会雑誌   41 ( 5 )   431 - 431   1999.8

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  • 軟骨成長因子CTGF/Hcs24の神経系における発現とその機能

    中西 徹, 大山 和美, 滝川 正春

    歯科基礎医学会雑誌   41 ( 5 )   411 - 411   1999.8

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  • 軟骨由来の成長因子CTGF/Hcs24の細胞内での動態と機能

    久保田 聡, 服部 高子, 志茂 剛, 中西 徹, 滝川 正春

    生化学   71 ( 8 )   892 - 892   1999.8

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  • 軟骨由来成長因子Hcs24/CTGFの腫瘍血管新生における役割

    志茂 剛, 中西 徹, 松村 智弘, 滝川 正春

    日本癌学会総会記事   58回   249 - 249   1999.8

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  • 骨生物学の進展,細胞分化と組織形成 軟骨由来の成長因子CTGF/Hcs24の骨形成における役割

    滝川 正春, 中西 徹, 志茂 剛, 西田 崇

    日本細胞生物学会大会講演要旨集   52回   26 - 26   1999.8

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  • 骨芽細胞の増殖と分化に与える軟骨由来成長因子CTGF/Hcs24の作用

    西田 崇, 中西 徹, 浅野 将宏, 志茂 剛, 玉谷 卓也, 手塚 克成, 滝川 正春

    生化学   71 ( 8 )   892 - 892   1999.8

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  • マウス肋骨骨折モデルにおける軟骨由来成長因子Hcs24/CTGFの発現

    浅海 浩二, 中西 徹, 浅野 将宏, 西田 崇, 浅原 弘嗣, 川井 章, 井上 一, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   17 ( 2 )   11 - 11   1999.6

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  • 軟骨由来成長因子Hcs24/CTGFのマウス胎生期における発現とCbfa1による制御

    中西 徹, 浅野 将宏, 山合 友一朗, 小守 寿文, 西田 崇, 吉道 玄, 服部 高子, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   17 ( 2 )   5 - 5   1999.6

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  • 軟骨由来の成長因子 Hcs24/CTGF(Ecogenin) の遺伝子発現調節メカニズム

    久保田 聡, 服部 高子, 中西 徹, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   17 ( 2 )   81 - 81   1999.6

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  • マウス歯根膜細胞株(MPL)におけるニューロトロフィンとTRKレセプターの発現とその機能

    坪井 佳子, 中西 徹, 山本 照子, 宮本 学, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   17 ( 2 )   173 - 173   1999.6

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  • 軟骨由来成長因子Hcs24/CTGFはヒト歯根膜由来線維芽細胞の増殖と分化を促進する

    浅野 将宏, 西田 崇, 中西 徹, 坪井 佳子, 吉道 玄, 山本 照子, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   17 ( 2 )   174 - 174   1999.6

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  • 軟骨由来成長因子Hcs24/CTGFはヘパラン硫酸に結合し軟骨細胞の接着を促進する

    西田 崇, 中西 徹, 志茂 剛, 浅野 将宏, 吉道 玄, 滝川 正春

    日本骨代謝学会雑誌   17 ( 2 )   82 - 82   1999.6

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  • Repressive Effect of the 3′-Untranslated Region in the Human Connective Tissue Growth Factor(CTGF)cDNA on Gene Expression.

    Kubota Satoshi, Hattori Takako, Nakanishi Tohru, Takigawa Masaharu

    Connective tissue   31 ( 2 )   125 - 125   1999.6

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  • The Role of Connective Tissue Growth Factor(CTGF)on Human Pulmonary Fibrosis

    Pan Li-Hua, Yamauchi Kohei, Uzuki Miwa, Yoshida Kohko, Nakanishi Toru, Takigawa Masaharu, Inoue Hiroshi, Sawai Takashi

    Connective tissue   31 ( 2 )   112 - 112   1999.6

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  • 慢性関節リウマチ患者における軟骨細胞分泌タンパク(YKL-39)に対する抗体の検出

    関根 太一, 増子 佳世, 松井 利浩, 浅原 弘嗣, 滝川 正春, 西岡 久寿樹, 加藤 智啓

    リウマチ   39 ( 2 )   429 - 429   1999.4

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  • 関節軟骨組織及び軟骨細胞におけるマトリックスメタロプロテアーゼと基質合成

    石黒 直樹, 伊藤 隆安, 小嶋 俊久, 酒井 忠博, 滝川 正春, 岩田 久

    日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association   73 ( 3 )   S590   1999.3

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  • アデノウイルスベクターを用いた軟骨細胞に対する遺伝子導入

    新井 祐志, 久保 俊一, 小林 括平, 高橋 謙治, 池田 巧, 大橋 鈴世, 今西 二郎, 滝川 正春, 平澤 泰介

    日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association   73 ( 2 )   S329   1999.2

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  • 軟骨性腫瘍における結合組織成長因子(CTGF)の発現

    杓永 俊彦, 尾崎 敏文, 中西 徹, 川井 章, 西田 圭一郎, 浅海 浩二, 柴原 基, 大原 信哉, 滝川 正春, 井上 一

    日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association   73 ( 2 )   S233   1999.2

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  • 慢性関節リウマチ関連抗原RA-A47は自己の発現レベルの低下にともない細胞膜へと局在が変化する

    服部高子, 油谷安孝, 藤沢拓生, 中西徹, 滝川正春

    日本分子生物学会年会プログラム・講演要旨集   22nd   1999

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  • Expression of connective tissue growth factor in cartilaginous tumors

    T Shakunaga, T Ozaki, S Ohara, K Asaumi, T Doi, K Nishida, A Kawai, M Shibahara, M Takigawa, H Inoue

    SIROT 99   737 - 742   1999

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  • Molecular function of chondrocyte-derived growth factor CTGF (Ecogenin)

    NAKANISHI Thru, SHIMO Tsuyoshi, NISHIDA Takashi, ASANO Masahiro, YOSHIMICHI Gen, TAMATANI Takuya, TEZUKA Katsunari, TAKIGAWA Masaharu

    21   488 - 488   1998.12

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  • The role of chondrocyte-derived growth factor CTGF (Ecogenin) in osteogenesis

    ASANO Masahiro, NAKANISHI Thru, NISHIDA Takashi, ASAUMI Koji, TAMATANI Takuya, TEZUKA Katsunari, TAKIGAWA Masaharu

    21   488 - 488   1998.12

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  • Cloning and characterization of ra-a47 gene which encodes 47 kDa of rheumatoid arthritis-related antigen (RA-A47) protein

    HATTORI Takako, YUTANI Yasutaka, FUJISAWA Takuo, NAKANISHI Tohru, TAKIGAWA Masaharu

    21   461 - 461   1998.12

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  • 変形性関節症軟骨におけるCTGFの局在

    柴原 基, 西田 圭一郎, 土井 武, 浅原 弘嗣, 井上 一, 中西 徹, 浅野 将宏, 志茂 剛, 西田 崇, 滝川 正春

    岡山医学会雑誌   110 ( 7〜10 )   165 - 165   1998.10

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  • 軟骨由来成長因子Hcs24/CTGF組換え蛋白質の軟骨細胞及び血管内皮細胞に対する増殖・分化促進作用

    浅野 将宏, 中西 徹, 志茂 剛, 西田 崇, 服部 高子, 滝川 正春

    歯科基礎医学会雑誌   40 ( 抄録 )   389 - 389   1998.9

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  • 軟骨由来成長因子Hcs24/CTGF受容体の同定と軟骨細胞の分化による受容体数の変動

    西田 崇, 中西 徹, 志茂 剛, 浅野 将宏, 服部 高子, 滝川 正春

    歯科基礎医学会雑誌   40 ( 抄録 )   389 - 389   1998.9

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  • Ex vivo Gene Transfer to Chondrocytes in the Cartilage Defect

    IKEDA T

    日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association   72 ( 8 )   S1445   1998.8

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  • Expression of Neurotrophin during Fracture Healing : In vivo Study

    ASAUMI K.

    72 ( 8 )   S1359   1998.8

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  • Novel Nonsteroidal Antiinflammatory Drug, JTE-522, Inhibits Messenger RNA Expression for Matrix Metalloproteinase in Chondrocyte, HCS-2/8, and Synovial Fibroblast of Rheumatoid Arthritis Patients

    ITO T.

    72 ( 8 )   S1328   1998.8

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  • Adenovirus vector-mediated gene transduction to chondrocytes

    ARAI Y., KUBO T., KOBAYASHI K., TAKAHASHI K., IKEDA T., OHASHI S., IMANISHI J., TAKIGAWA M., HIRASAWA Y.

    72 ( 8 )   S1748   1998.8

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  • Activation of NF-κB in Human Chondrosarcoma HCS-2/8 Cells

    SAKAI T.

    72 ( 8 )   S1688   1998.8

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  • CTGFの慢性関節リウマチ(RA),変形性関節症(OA)膝関節における局在

    柴原 基, 西田 圭一郎, 中西 徹, 浅原 弘嗣, 土井 武, 志茂 剛, 浅野 将宏, 西田 崇, 井上 一, 滝川 正春

    日本整形外科学会雑誌   72 ( 8 )   s1686 - s1686   1998.8

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  • 軟骨由来成長因子Hcs24/CTGFの組換え蛋白質の血管新生作用

    志茂 剛, 中西 徹, 松村 智弘, 滝川 正春

    日本癌学会総会記事   57回   177 - 177   1998.8

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  • 軟骨由来成長因子Hcs24/CTGF組換え蛋白質の内軟骨性骨化促進作用

    中西 徹, 志茂 剛, 西田 崇, 浅野 将宏, 服部 高子, 玉谷 卓也, 手塚 克成, 滝川 正春

    生化学   70 ( 8 )   975 - 975   1998.8

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  • 細胞膜受容体 軟骨由来成長因子Hcs24/CTGF受容体の同定と軟骨細胞の分化に伴う変動

    西田 崇, 中西 徹, 志茂 剛, 浅野 将宏, 服部 高子, 玉谷 卓也, 手塚 克成, 滝川 正春

    生化学   70 ( 8 )   805 - 805   1998.8

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  • 軟骨由来成長因子Hcs24/CTGFの組換え蛋白質は軟骨細胞と血管内皮細胞に働いて内軟骨性骨化を促進する

    中西 徹, 志茂 剛, 西田 崇, 浅野 将宏, 服部 高子, 玉谷 卓也, 手塚 克成, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   16 ( 2 )   28 - 28   1998.7

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  • 軟骨由来成長因子Hcs24/CTGFの特異的受容体の同定と内軟骨性骨化における意義

    西田 崇, 中西 徹, 志茂 剛, 浅野 将宏, 服部 高子, 玉谷 卓也, 手塚 克成, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   16 ( 2 )   27 - 27   1998.7

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  • 慢性関節リウマチ関連抗原蛋白RA-A47 cDNAの単離と抗原提示機構

    服部 高子, 油谷 安孝, 佐々木 和浩, 藤沢 拓生, 中西 徹, 高橋 浩二郎, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   16 ( 2 )   4 - 4   1998.7

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  • マウス肋骨骨折モデルにおける神経栄養因子の発現

    浅海 浩二, 中西 徹, 志茂 剛, 浅原 弘嗣, 井上 一, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   16 ( 2 )   286 - 286   1998.7

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  • 軟骨細胞の基質合成におけるメカニカルストレスの影響

    藤沢 拓生, 服部 高子, 佐々木 和浩, 高橋 浩二郎, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   16 ( 2 )   109 - 109   1998.7

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  • Induction of in vitro angiogenesis by recombinant chondrocyte-derived growth factor Hcs24 / CTGF

    Shimo T., Nakanishi T., Nishida T., Asano M., Hattori T., Matsumura T., Takigawa M.

    Connective tissue   30 ( 2 )   153 - 153   1998.6

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  • The Biological Aspects of OA Treatment with Hyaluronic Acid Injection and Cox-2 Inhibitor : The Effects on the mRNA Expression of Matrix Metalloproteinase

    ISHIGURO N.

    72 ( 2 )   S307   1998.2

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  • Effect of cyclic mechanical stress on chondrocyte metabolism.

    T Fujisawa, T Hattori, T Kuboki, A Yamashita, M Takigawa

    JOURNAL OF DENTAL RESEARCH   77   1004 - 1004   1998

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  • Pachyonychia congenita type 2: Keratin 17 mutation in a Japanese case

    W. Fujimoto, G. Nakanishi, S. Hirakawa, T. Nakanishi, T. Shimo, M. Takigawa, J. Arata

    Journal of the American Academy of Dermatology   38 ( 6 I )   1007 - 1009   1998

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    DOI： 10.1016/S0190-9622(98)70170-7

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  • VEGF.

    服部高子, 滝川正春

    関節外科   17 ( 7 )   1998

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  • IL-6 activates fibroblasts in the presence of soluble IL-6 receptor.

    K Naruishi, S Takashiba, M Takigawa, F Nishimura, H Arai, Y Murayama

    JOURNAL OF DENTAL RESEARCH   77   866 - 866   1998

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  • Adenovirus Vector-mediated Gene Transfer to Joints in Guinea Pig

    IKEDA T

    日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association   71 ( 8 )   S1564   1997.8

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  • Development of Gene Regulation System for Gene Therapy for Arthritis

    ARAI Y.

    71 ( 8 )   S1382   1997.8

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  • 神経栄養因子の機能を介する骨粗鬆症の予防法の確立 培養骨芽細胞を用いた各種ビタミンの効果に関する基礎的検討

    滝川 正春, 中西 徹, 志茂 剛

    Osteoporosis Japan   5 ( 3 )   604 - 608   1997.8

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  • Possible roles of connective tissue growth factor (CTGF)-related gene in angiogenesis.

    T Endo, T Nakanishi, Y Kimura, T Hatton, T Nishida, T Matsumura, M Takigawa

    FASEB JOURNAL   11 ( 9 )   A1451 - A1451   1997.7

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  • Expression and heterozygosity of imprinting IGF-II and H19 in the human chondrosarcoma-derived cells. HCS-2/8 and -2/A

    K Takahashi, TH Vu, T Hattori, T Nakanishi, AR Hoffman, M Takigawa

    FASEB JOURNAL   11 ( 9 )   A937 - A937   1997.7

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  • Cloning of a mRNA preferentially expressed in chondrocytes by differential display-PCR: Identity with connective tissue growth factor (CTGF) mRNA.

    T Nakanishi, Y Kimura, T Tamura, H Ichikawa, Y Yamaai, T Sugimoto, M Takigawa

    FASEB JOURNAL   11 ( 9 )   A1109 - A1109   1997.7

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  • 軟骨由来多機能成長因子CTGF/Hcs24の内軟骨性骨形成における役割 : 軟骨・血管・神経における発現と作用機構

    中西 徹, 遠藤 剛, 西田 崇, 服部 高子, 竹林 俊明, 松村 智弘, 石関 清人, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   15 ( 2 )   23 - 23   1997.6

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  • 軟骨由来慢性関節リウマチ関連抗原蛋白RA-A47 : HSP47との異同と炎症性サイトカインによる発現の抑制

    服部 高子, 油谷 安孝, 佐々木 和浩, 藤沢 拓生, 中西 徹, 高橋 浩二郎, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   15 ( 2 )   226 - 226   1997.6

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  • Identification of Protein Tyrosine Phosphatase Related to the Cell Density-Dependent Growth Inhibition of Murine Osteoblastic cells.

    高橋浩二郎, 森川雅之, 服部高子, 中西徹, 滝川正春

    日本分子生物学会年会プログラム・講演要旨集   20th   1997

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  • Function of a HSP47-Like Rheumatoid Arthritis-Related Antigen(RA-A47).

    服部高子, 油谷安孝, 佐々木和浩, 藤沢拓生, 中西徹, 高橋浩二郎, 滝川正春

    日本分子生物学会年会プログラム・講演要旨集   20th   1997

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  • Relation between cartilage destruction and neovascularization in arthritis : IL-1 accelerates not only liberation of bFGF from cultured cartilage cells but also the production and the gene expression.

    佐々木和浩, 服部高子, 藤沢拓生, 中西徹, 高橋浩二郎, 井上一, 滝川正春

    日本骨代謝学会雑誌   15 ( 2 )   1997

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  • Connective Tissue Growth Factor Mediates TGF-β-stimulated DNA Synthesis in a Human Chondrocytic Cell Line Acting Through Its Specific Receptors.

    西田崇, 中西徹, 志茂剛, 服部高子, 浅野将宏, 玉谷卓也, 手塚克成, 滝川正春

    日本分子生物学会年会プログラム・講演要旨集   20th   1997

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  • Gene Transfer to Chondrocytes Using Adenovirus Vector

    ARAI Y

    日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association   70 ( 8 )   S1270   1996.8

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  • Analysis of Heat Shock Protein(HSP) in Chondrocytes with Gene Transfer

    IKEDA T.

    70 ( 8 )   S1271   1996.8

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  • IL-1 Induces Release of Chondrocyte-associated b-FGF and Production of b-FGF by Chondrocytes

    SASAKI K.

    70 ( 8 )   S1194   1996.8

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  • ヒト軟骨肉腫由来の軟骨細胞様培養細胞株でのIGF-II遺伝子の転写制御因子遺伝子の発現変動

    高橋 浩二郎, 服部 高子, 木村 祐輔, 中西 徹, 滝川 正春

    日本分子生物学会年会プログラム・講演要旨集   19   796 - 796   1996.8

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  • 軟骨細胞増殖因子Hcs24/CTGFのヒト軟骨細胞様細胞株(HCS-2/8)に対する作用機序

    西田 崇, 中西 徹, 木村 祐輔, 遠藤 剛, 服部 高子, 高橋 浩二郎, 滝川 正春

    日本分子生物学会年会プログラム・講演要旨集   19   171 - 171   1996.8

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  • 軟骨細胞増殖因子Hcs24/CTGFの血管新生における作用

    遠藤 剛, 中西 徹, 木村 祐輔, 服部 高子, 西田 崇, 村上 崇子, 滝川 正春

    日本分子生物学会年会プログラム・講演要旨集   19   171 - 171   1996.8

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  • 軟骨細胞増殖因子Hcs24/CTGF遺伝子の神経系における発現

    中西 徹, 大山 和美, 遠藤 剛, 浅沼 幹人, 小川 紀雄, 滝川 正春

    日本分子生物学会年会プログラム・講演要旨集   19   171 - 171   1996.8

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  • 慢性関節リウマチ関連抗原蛋白(RA-A47)の構造と性質

    服部 高子, 佐々木 和浩, 油谷 安孝, 木村 祐輔, 中西 徹, 高橋 浩二郎, 永田 和宏, 滝川 正春

    日本分子生物学会年会プログラム・講演要旨集   19   179 - 179   1996.8

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  • ヒト軟骨肉腫由来軟骨細胞様培養細胞株HCS-2/8におけるigf-II遺伝子プロモータの発現変動に対するアスコルビン酸の影響

    高橋 浩二郎, 服部 高子, 木村 祐輔, 中西 徹, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   14 ( 2 )   173 - 173   1996.6

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  • CD44を介する軟骨細胞のヒアルロン酸への細胞接着の軟骨成長における役割 : 軟骨細胞株HCS-2/8の増殖とTGF-β発現の促進

    石田 治, 田中 良哉, 森本 勲夫, 滝川 正春, 江藤 澄哉

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   14 ( 2 )   72 - 72   1996.6

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  • 軟骨特異的CTGF関連遺伝子hcs24の単離とその機能解析

    中西 徹, 木村 祐輔, 田村 知雄, 遠藤 剛, 西田 崇, 村上 崇子, 服部 高子, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   14 ( 2 )   51 - 51   1996.6

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  • ヒト軟骨細胞様細胞株(HCS-2/8)由来の慢性関節リウマチ関連抗原RA-A47 : その構造と性状

    服部 高子, 油谷 安孝, 佐々木 和浩, 中西 徹, 高橋 浩二郎, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   14 ( 2 )   71 - 71   1996.6

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  • Scrotal angiokeratoma in a young man

    T Hisa, S Taniguchi, Y Goto, H Teramae, K Osato, K Kakudo, M Takigawa

    ACTA DERMATO-VENEREOLOGICA   76 ( 3 )   248 - 249   1996.5

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    Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)  

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  • Scrotal angiokeratoma in a young man

    T Hisa, S Taniguchi, Y Goto, H Teramae, K Osato, K Kakudo, M Takigawa

    ACTA DERMATO-VENEREOLOGICA   76 ( 1 )   75 - 75   1996.1

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  • Gene Expression Regulation of Cartilage Extracellular Matrix by Hydrostatic Pressure

    TAKAHASHI K

    日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association   69 ( 8 )   S1742   1995.8

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  • The Contribution of c-fos DNA to Chondrocyte Metabolism : A Transfection Study

    TSUJI M.

    69 ( 8 )   S1433   1995.8

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  • インターロイキンー1(IL1)はNO産生を介して軟骨細胞から血管新生因子を遊離させる

    田村 知雄, 中西 徹, 木村 祐輔, 服部 高子, 村上 崇子, 乗松 尋道, 高橋 浩二郎, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   13 ( 2 )   59 - 59   1995.7

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  • Differential Display 法による軟骨特異的遺伝子のクローニング

    中西 徹, 木村 祐輔, 田村 知雄, 村上 崇子, 服部 高子, 高橋 浩二郎, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   13 ( 2 )   252 - 252   1995.7

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  • ヒト軟骨肉腫由来の軟骨培養細胞株(HCS-2/8)におけるIGF-II遺伝子の過剰発現, 発現プロモーター変動およびゲノムインプリンティング

    高橋 浩二郎, 木村 祐輔, 服部 高子, 中西 徹, 田村 知雄, 滝川 正春

    日本骨代謝学会雑誌 = Japanese journal of bone metabolism   13 ( 2 )   307 - 307   1995.7

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  • FURTHER CHARACTERIZATION OF A HUMAN CHONDROSARCOMA-DERIVED CHONDROCYTIC CELL LINE: HCS-2/8

    TAKIGAWA Masaharu, TAKAHASHI Kojiro, NAKANISHI Tohru, HATTORI Takako, KIMURA Yusuke, PAN Hai-Ou, KINOSHITA Akihiro, NAKAJIMA Kaoru, SUZUKI Fujio, NOMURA Shintaro, OKAWA Tokutaro, ZHU Jing-de

    13 ( 1 )   40 - 40   1995

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  • Transcriptional regulation of igf-II gene in a human chondrosarcoma cell line HCS-2/8: Alteration of the expressed promoters by ascorbic acid.

    高橋浩二郎, 服部高子, 木村祐輔, 松尾智江, 坪井佳子, 田村知雄, 中西徹, 井上一, 滝川正春

    日本分子生物学会年会プログラム・講演要旨集   18th   1995

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  • Characterization of a rheumatoid arthritis-related antigen purified from a human chondrocytic cell line.

    服部高子, 田村知雄, 佐々木和浩, 木村祐輔, 油谷安孝, 中西徹, 高橋浩二郎, 滝川正春

    日本分子生物学会年会プログラム・講演要旨集   18th   1995

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  • Phosphorylation of purified NarL protein and interactions among NarL, FNR and IHF on E. coli nar operon.

    服部高子, 高橋浩二郎, 中西徹, 神藤平三郎, 谷口茂彦, 滝川正春

    日本分子生物学会年会プログラム・講演要旨集   17th   1994

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  • ESTABLISHMENT OF A CLONAL HUMAN CHONDROSARCOMA CELL-LINE THAT PRODUCES AN ANTI-TUMOR FACTOR WITH ANTIANGIOGENIC ACTIVITY

    M TAKIGAWA, HO PAN, M ENOMOTO, A KINOSHITA, Y NISHIDA, F SUZUKI, Y TAKANO, K TAJIMA

    ANTICANCER RESEARCH   8 ( 5 )   1100 - 1100   1988

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  • ULTRASTRUCTURE AND ODC ACTIVITY OF ISOLATED CHONDROCYTES - EFFECTS OF CYTOCHALASIN-B AND COLCHICINE

    S MORITA, O URATA, H OZAWA, T TAKANO, M TAKIGAWA, F SUZUKI

    JOURNAL OF DENTAL RESEARCH   64 ( 4 )   742 - 742   1985

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  • ウサギ頭蓋・顔面軟骨より分離した軟骨培養細胞の分化機能 および 増殖に対するハイドロコーチゾンの促進作用

    高野照子, 中川浩一, 井上博之, 作田 守, 滝川正春, 鈴木不二男

    歯基礎誌   27 ( 2 )   450 - 457   1985

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  • CYTOSKELETON AND DIFFERENTIATION - EFFECTS OF CYTOCHALASIN-B AND COLCHICINE ON EXPRESSION OF THE DIFFERENTIATED PHENOTYPE OF CHONDROCYTES IN CULTURE

    F SUZUKI, M TAKIGAWA, T TAKANO, E SHIRAI

    CALCIFIED TISSUE INTERNATIONAL   36 ( 4 )   473 - 473   1984

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  • CYTOSKELETON AND THE DIFFERENTIATED PHENOTYPE OF CHONDROCYTES IN CULTURE

    T TAKANO, E SHIRAI, M OKADA, M SAKUDA, M TAKIGAWA, K FUKUO, F SUZUKI

    JOURNAL OF DENTAL RESEARCH   62 ( 4 )   467 - 467   1983

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  • CHARACTERISTICS OF CULTURED CHONDROCYTES FROM RABBIT NASAL-SEPTUM AND MANDIBULAR CONDYLE

    M OKADA, T DOI, M SAKUDA, M TAKIGAWA, T TAKANO, F SUZUKI

    JOURNAL OF DENTAL RESEARCH   59   927 - 927   1980

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Presentations

  • Positive Regulation of S-Adenosylmethionine on Chondrocyte Differentiation Via Stimulation of Polyamine Production and the Gene Expression of Cellular Communication Network factor 2, Cartilage-Specific ECM and Its Synthesizing Enzymes. International conference

    Takigawa M, Hoang LD, Hiasa M, Omote H, Nishida T, Hattori T, Kawata K, Kubota S, Kuboki T, Aoyama E

    The 12th International Workshop on the CCN Family of Genes  2024.6.24 

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    Event date： 2024.6.20 - 2024.6.23

    Language：English  

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  • S-adenosylmethionine enhances chondrocyte differentiation via polyamine and chondrogenesis-related gene expression. International conference

    Hoang, L, Aoyama, E, Hiasa, M, Omote, H, Kuboki, T, Kubota, S, Takigawa, M

    102nd IADR General session  2024.3 

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    Event date： 2024.3.13 - 2024.3.16

    Language：English   Presentation type：Poster presentation  

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  • Correlation between High Expression of CCN3 and Osteoarthritis in hip joints. International conference

    Hirose, K, Kuwahara, M, Nakata, E, Tetsunaga, T, Yamada, K, Koura, T, Inoue, T, Takigawa, M, Ozaki, T, Kubota, S, Hattori, T

    Orthopaedic Research Society 2023 Annual Meeting. February 

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    Event date： 2023.2.10 - 2023.2.14

    Language：English   Presentation type：Poster presentation  

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  • Regulation of chondrocyte differentiation by CCN2 through binding to GDF5 and its receptors. International conference

    Higashihara, N, Aoyama, E, Furumatsu, T, Kubota, S, Ozaki, T, Takigawa, M

    Orthopaedic Research Society 2023 Annual Meeting. 

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    Event date： 2023.2.10 - 2023.2.14

    Language：English   Presentation type：Poster presentation  

    Venue：Dallas, TX  

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  • Role of CCN2 produced by osteocytes in bone remodeling Invited International conference

    Nishida T, Kubota S, Yokoi H, Mukoyama M, Takigawa, M

    Tenth International Workshop on the CCN Family of Genes  2019.10.21  International CCN Society

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    Event date： 2019.10.21 - 2019.10.24

    Presentation type：Symposium, workshop panel (nominated)  

    Venue：International CCN Society  

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  • Long noncoding RNAs that regulate CCN2. Invited

    Kubota S, Ishikawa T, Mizukawa T, Kondo S, El-Seoudi A, Takashi Nishida T, Hattori T, Kawata K, Furumatsu T, Takarada T, Ono M, Takigawa M

    Tenth International Workshop on the CCN Family of Genes 

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    Event date： 2019.10.21 - 2019.10.24

    Presentation type：Symposium, workshop panel (nominated)  

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  • Small compounds that turn on CCN family genes. Invited International conference

    Kubota S, Hara ES, Akashi S, Ono M, Nishida T, Hattori T, Kuboki T, Takigawa M

    Ninth International Workshop on the CCN Family of Genes  2017 

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    Event date： 2017.11.2 - 2017.11.7

    Presentation type：Symposium, workshop panel (nominated)  

    Venue：Saint-Malo  

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  • CCN proteins as targets for skeletal regulation theraphy. Ninth International Workshop on the CCN Family of Genes International conference

    Takigawa M, Hara C, Kamatsuki Y, Aoyama E, Janune D, Furumatsu T, Nishida T, Hattori T, Yamanaka N, Kamioka H, Ozaki T, Kubota S

    Ninth International Workshop on the CCN Family of Genes 

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    Event date： 2017.11.2 - 2017.11.7

    Presentation type：Symposium, workshop panel (nominated)  

    Venue：Saint-Malo  

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  • Roles of CCN Proteins in Skeletal Growth, Homeostasis and Regeneration. Invited

    Takigawa M

    Meet-A-Mentor Lunch for New Investigators (Oral Biology). 94th IADR General Session 

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    Event date： 2016.6.22 - 2016.6.25

    Presentation type：Symposium, workshop panel (nominated)  

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  • LONG NONCODING RNAS THAT REGULATE CCN2 International conference

    Satoshi Kubota, Takanori Ishikawa, Tomomi Mizukawa, Sei Kondo, Abdellatif El-Seoudi, Takashi Nishida, Takako Hattori, Kazumi Kawata, Takayuki Furumatsu, Takeshi Takarada, Mitsuaki Ono, Masaharu Takigawa

    10th International Workshop of the CCN Family of Genes  2019.10.23 

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    Language：English   Presentation type：Symposium, workshop panel (nominated)  

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  • ROLE OF CCN2 PRODUCED BY OSTEOCYTES IN BONE REMODELING International conference

    Takashi Nishida, Satoshi Kubota, Hideki Yokoi, Masashi Mukoyama, Masaharu Takigawa*(presenter)

    10th International Workshop of the CCN Family of Genes  2019.10.23 

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  • Palovarotene, the Selective Agonist for Nuclear Retinoic Acid Receptor Gamma, Inhibits Glycosaminoglycan Production and Decreases Tumor Mass Size in a Chondrosarcoma Cell Line both in vitroand in vivo International conference

    Shield W, Dan Y, Cellini A, Takigawa M, Iwamoto M, Enomoto-Iwamoto M, Ng VY

    The American Academy of Orthopaedic Surgeons 2019 Annual Meeting  2019.3.12 

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  • Regenerative effect of low-intensity pulsed ultrasound (LIPUS) on meniscus International conference

    Kamatsuki, Y, Aoyama, E, Furumatsu, T, Miyazawa, S, Maehara, A, Nishida, T, Kubota, S, Takikgawa, M, Ozaki, T

    ORS Annual meeting 2019  2019.2.4 

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  • Palovarotene, the Selective Agonist for Nuclear Retinoic Acid Receptor Gamma, Inhibits Proteoglycan Production and Decreases Tumor Mass Size in Chondrosarcoma Cell Line Cells

    Shield W, Dan Y, Cellini A, Takigawa M, Garcia1 S, Iwamoto M, Ng VY, Enomoto-Iwamoto M

    2019 ORS Annual meeting  2019.2.3 

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  • Palovarotene, the Selective Agonist for Nuclear Retinoic Acid Receptor Gamma, Inhibits Proteoglycan Production and Decreases Tumor Mass Size in Chondrosarcoma Cell Line Cells. International conference

    William Shield, Yang Dan, Ashley Cellini, Masaharu Takigawa, Sonia Garcia, Masahiro Iwamoto, Vincent Ng, Motomi Enomoto-Iwamoto

    ORS Annual meeting 2019  2019.2.2 

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  • Catabolic Effects of FGF-1 on Chondrocytes through MMP-13 and CCN2: Possible role in Osteoarthritis

    The 2018 OARSI Congress  2018 

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  • Fibroblast Growth Factor 1 (FGF-1) impinges on Chondrocyte Degradation in OA through Matrix Metalloproteinase 13 (MMP-13) and Connective Tissue Growth Factor (CCN2)

    The 2018 ASBMR Symposium – Skeletal Contributions to Joint Degeneration and Osteoarthritis  2018 

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  • Fibroblast Growth Factor 1 (FGF-1) impinges on Chondrocyte Degradation in OA through Matrix Metalloproteinase 13 (MMP-13) and Connective Tissue Growth Factor (CCN2)

    The 2018 ASBMR annual meeting  2018 

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  • Catabolic effects of FGF-1 on chondrocytes with reduced CCN2 production and its possible role in osteoarthritis

    Ninth International Workishop on the CCN Family of Genes  2017 

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  • CCN proteins as targets for skeletal regulation theraphy

    Ninth International Workishop on the CCN Family of Genes  2017 

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  • Small compounds that turn on CCN family genes

    Ninth International Workishop on the CCN Family of Genes  2017 

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  • Roles of CCN Proteins in Skeletal Growth, Homeostasis and Regeneration.

    Takigawa M

    Invited Special Lecture at University of Bordeaux  2016.5.19 

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  • Clarification of molecular mechanism of CCN2 and CCN3 actions on cartilage development and its application to toward regenerative and anti-aging therapeutics.

    Takigawa M

    Clarification of molecular mechanism of CCN2 and CCN3 actions on cartilage development and its application to toward regenerative and anti-aging therapeutics. Invited Special Lecture at Dental School, National University of Singapore  2015.7.1 

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  • The Roles of CCN Proteins in Skeletal Growth, Maintenance and Regeneration.

    Takigawa M

    Invited Special Seminar at Harvard University Medical School  2015.3.13 

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  • Regenerative effects of CCN2 ondependent modules and CCN3 on articular chondrocytes/cartilage

    Eight International Workshop on the CCN Family of Genes  2015 

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  • Metabolic impacts of CCN2 in chondrocytes

    Eight International Workshop on the CCN Family of Genes  2015 

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  • Induction of CCN2 by low-intensity pulsed ultrasound (LIPUS) in cultured chondrocytes and its biological significance

    Eight International Workshop on the CCN Family of Genes  2015 

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    2024.6 

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    Event date： 2024.6.29 - 2024.7.2

    Presentation type：Oral presentation (general)  

    Venue：那覇、沖縄  

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  • 核移行したCCN2は転写共役因子として作用し、軟骨細胞分化を制御する。

    西田 崇, 長尾有里香, 滝川正春, 久保田聡

    第42回日本骨代謝学会 

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    Event date： 2024.6.29

    Presentation type：Oral presentation (general)  

    Venue：那覇、沖縄  

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  • C-Type lectin receptor CD302 increases osteoblast adhesion and survival. International conference

    Hoang, L, Aoyama, E, Hiasa, M, Omote, H, Kuboki, T, Kubota, S, Takigawa, M

    102nd IADR General session  2024 

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    Event date： 2024.3.13 - 2024.3.16

    Presentation type：Oral presentation (general)  

    Venue：New Orleans, LA  

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  • CCN2がGDF5およびその受容体との結合を介して軟骨細胞分化に及ぼす影響の検討。

    東原直裕, 青山絵理子, 古松毅之, 久保田聡, 尾﨑敏文, 滝川正春

    第36回日本軟骨代謝学会  2024.2.16 

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    Event date： 2024.2.17

    Presentation type：Poster presentation  

    Venue：大阪  

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  • 股関節における変形性股関節症関連遺伝子の網羅的解析

    奥田龍一郎, 廣瀬一樹, 中田英二, 鉄永智紀, 山田和希, 小浦 卓, 井上智博, 滝川正春, 尾崎敏文, 久保田聡, 服部高子

    第36回日本軟骨代謝学会  2024.2 

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    Event date： 2024.2.16 - 2024.2.17

    Presentation type：Poster presentation  

    Venue：大阪  

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  • 軟骨細胞分化においてPPARγが機能する可能性。

    畚野里紗, 河田かずみ, 滝川正春, 上岡 寛, 久保田聡

    第36回日本軟骨代謝学会  2024 

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    Event date： 2024.2.16 - 2024.2.17

    Presentation type：Oral presentation (general)  

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  • S-アデノシルメチオニンによる軟骨細胞保護作用のメカニズム：ポリアミン合成と軟骨細胞関連遺伝子発現の相互作用

    Hoang, L, Aoyama, E, Hiasa, M, Omote, H, Kubota, S, Kuboki, T, Takigawa, M

    第36回日本軟骨代謝学会  2024 

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    Event date： 2024.2.16 - 2024.2.17

    Presentation type：Poster presentation  

    Venue：大阪  

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  • 軟骨細胞における核内CCN2の生理的役割

    西田 崇, 長尾有里香, 滝川正春, 久保田聡

    第36回日本軟骨代謝学会  1900 

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    Event date： 2024.2.16 - 2024.2.17

    Presentation type：Oral presentation (general)  

    Venue：大阪  

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  • 軟骨組織の加齢とともに発現が上昇するCCN3は、その発現上昇と軟骨変性度が年齢、荷重の有無に関わらず相関する。

    桑原実穂, 廣瀬一樹, 近藤 星, Fu Shanqi, 大野充昭, 古松毅之, 中田英二, 滝川正春, 久保田聡, 服部 高子

    第96回日本生化学会  2023 

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    Event date： 2023.11.2

    Presentation type：Poster presentation  

    Venue：福岡  

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  • Positive regulation of S-adenosylmethionine on chondrocytic differentiation via stimulation of polyamine production and gene expression of chondrocytic differentiation factors.

    Hoang, L, Aoyama, E, Kubota, S, Kuboki, T, Takigawa, M

    第96回日本生化学会  2023 

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    Event date： 2023.10.31 - 2023.11.2

    Presentation type：Poster presentation  

    Venue：福岡  

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  • GDF5およびその受容体との結合を介したCCN2の軟骨細胞分化制御機構

    東原直裕, 青山絵理子, 久保田聡, 尾﨑敏文, 滝川正春

    第38回日本整形外科学会基礎学会 

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    Event date： 2023.10.19 - 2023.10.20

    Presentation type：Poster presentation  

    Venue：筑波  

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  • 線維化を制御するPU.1発現に対する核移行したCCN2の作用。

    西田 崇, 滝川正春, 久保田聡

    第64回 歯科基礎医学会  2022.9 

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    Event date： 2023.9.17 - 2023.9.19

    Presentation type：Oral presentation (general)  

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  • Positive regulation of S-adenosylmethionine on chondrocytic differentiation via stimulation of polyamine production and gene expression of chondrogenic differentiation factors.

    Hoang, L, Aoyama, E, Kubota, S, Kuboki, T, Takigawa, M

    第65回歯科基礎医学会 

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    Event date： 2023.9.16 - 2023.9.18

    Presentation type：Oral presentation (general)  

    Venue：東京  

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  • CCN3は軟骨細胞老化マーカーであり、年齢、荷重の有無に関わらず変形性関節症と相関する。

    服部高子, 滝川正春, 久保田聡

    第65回歯科基礎医学会  2023 

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    Event date： 2023.9.16 - 2023.9.17

    Presentation type：Oral presentation (general)  

    Venue：東京  

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  • 軟骨細胞におけるCCN2由来circRNAの発現とその機能の可能性。

    加藤壮真, 河田かずみ, 西田 崇, 滝川正春, 久保田聡

    第65回歯科基礎医学会  2023 

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    Event date： 2023.9.16 - 2023.9.17

    Presentation type：Oral presentation (general)  

    Venue：東京  

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  • Intraflagellar transport protein 88によるHippo経路と古典的WNT経路を介した象牙芽前駆細胞増殖制御の可能性。

    河田かずみ, 青山 絵理子, 滝川正春, 久保田聡

    第65回歯科基礎医学会 

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    Event date： 2023.9.16 - 2023.9.17

    Presentation type：Oral presentation (general)  

    Venue：東京  

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  • Positive regulation of S-adenosylmethionine on chondrocytic differentiation via stimulation of polyamine production and gene expression of chondrogenic differentiation factors.

    Hoang, L, Aoyama, E, Hiasa, M, Omote, H, Kubota, S, Kuboki, T, Takigawa, M

    第14回日本CCNファミリー研究会  2023.9.2 

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    Event date： 2023.9.2

    Presentation type：Oral presentation (general)  

    Venue：岡山  

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  • CCN2とGDF5およびその受容体との結合の解析と軟骨細胞における意義。

    東原直裕, 青山絵理子, 古松毅之, 久保田聡, 尾﨑敏文, 滝川正春

    第14回日本CCNファミリー研究会  2023.9.2 

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    Event date： 2023.9.2

    Presentation type：Oral presentation (general)  

    Venue：岡山  

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  • Positive regulation of S-adhenosylmethione on chondrocytic differentiation via stimulation of polyamine production and gene expression of chondrogenitic differentiation factors.

    Hoang, L, Aoyama, E, Hiasa, M, Omote, H, Kubota, S, Kuboki, T, Takigawa, M

    第41回日本骨代謝学会  2023.7.27 

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    Event date： 2023.7.27 - 2023.7.29

    Presentation type：Poster presentation  

    Venue：東京  

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  • 軟骨細胞での生物学的作用における Hippo pathway を介した CCNs と PDGFRL の関与

    河田かずみ, 青山絵理子, 滝川正春, 久保田聡

    第41回日本骨代謝学会  2023.7 

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    Event date： 2023.7.27 - 2023.7.29

    Presentation type：Oral presentation (general)  

    Venue：東京  

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  • CCN2 は GDF5 およびその受容体との結合を介して軟骨細胞分化を制御する。

    東原直裕, 青山絵理子, 古松毅之, 久保田聡, 尾﨑敏文, 滝川正春

    第41回日本骨代謝学会 

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    Event date： 2023.7.27 - 2023.7.29

    Presentation type：Oral presentation (general)  

    Venue：東京  

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  • C 型レクチン受容体 CD302 を介した骨芽細胞の接着および遊走制御機構の解明。

    青山絵理子, 久保田聡, 滝川正春

    第41回日本骨代謝学会 

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    Event date： 2023.7.27 - 2023.7.29

    Presentation type：Oral presentation (general)  

    Venue：東京  

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  • 軟骨細胞における CCN2 由来 circRNAの発現および機能の探索。

    加藤壮真, 河田かずみ, 西田 崇, 水川朋美, 滝川正春, 久保田聡

    第41回日本骨代謝学会 

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    Event date： 2023.7.27 - 2023.7.29

    Presentation type：Oral presentation (general)  

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  • 線維化におけるCCN2の転写共役様因子としての作用

    西田 崇, 辰川ひなた, 滝川正春, 久保田聡

    第55回日本結合組織学会  2023.6 

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    Event date： 2023.6.24 - 2023.6.25

    Presentation type：Oral presentation (general)  

    Venue：岡山  

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  • 41. ホアン ディン ロック、青山絵理子、日浅未来、表弘志、久保田聡、 窪木拓男、滝川正春: S- アデノシルメチオニンは、ポリアミン合成と分化関連遺伝子発現を促進することにより、軟骨細胞の分化を調節する。

    ホアン ディン ロック, 青山絵理子, 日浅未来, 表弘志, 久保田聡, 窪木拓男, 滝川正春

    第55回日本結合組織学会  2023.6 

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    Event date： 2023.6.24 - 2023.6.25

    Presentation type：Oral presentation (general)  

    Venue：岡山  

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  • BMP2 及び RANKL への結合を介した口腔がん細胞の骨転移に対するCCN6の2つの作用。

    芳地浩彰, 久保田聡, 滝川正春, 西田 崇

    第55回日本結合組織学会  2023.6 

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    Event date： 2023.6.24 - 2023.6.25

    Presentation type：Oral presentation (general)  

    Venue：岡山  

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  • CCN2 は BMPRIb を介して軟骨細胞における GDF5 の生理活性を抑制する。

    東原直裕, 青山絵理子, 古松毅之, 久保田聡, 尾崎敏文, 滝川正春

    第55回日本結合組織学会  2023.6 

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    Event date： 2023.6.24

    Presentation type：Oral presentation (general)  

    Venue：岡山  

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  • S-アデノシルメチオニンは軟骨細胞のポリアミン合成および成長因子遺伝子発現を介して分化を促進する。

    ホアンディン ロック, 青山絵理子, 日浅未来, 表 弘志, 久保田聡, 窪木拓男, 滝川正春

    第35回日本軟骨代謝学会  2023.3 

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    Event date： 2023.3.3 - 2023.3.4

    Presentation type：Poster presentation  

    Venue：横浜  

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  • Effective regulation of S-adenosylmethionie on chondrocyte differentiation via interstimulation of polyamine production and gene expression of growth factors

    Hoang, L, Aoyama, E, Hiasa, M, Omote, H, Kubota, S, Kuboki, T, Takigawa

    2022.11.30 

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    Event date： 2022.11.30 - 2022.12.2

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  • C

    青山絵理子, 久保田聡, 滝川正春

    2022.11.30 

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    Event date： 2022.11.30 - 2022.12.2

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  • 軟骨細胞におけるメトホルミンによるlong non-coding RNA, UCA1およびCCN2の発現制御

    回日本分子生物学会, 日本生物物理学会, 共催

    近藤 星;服部高子;桑原実穂;Fu Shanqi;西田 崇;薬師寺翔太;吉岡洋祐;森谷徳文;飯田征二;滝川正春;久保田聡;  2022.11.30 

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    Event date： 2022.11.30 - 2022.12.2

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  • 線維化を制御するPU.1とCCN2発現に対するCCN2のイントラクリン作用

    西田 崇, 滝川正春, 久保田聡

    第95回日本生化学会 。、2022, 11, 9-11, 名古屋  2022.11.9 

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    Event date： 2022.11.9 - 2022.11.11

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  • 軟骨組織の加齢変性におけるCCN3の機能。

    桑原実穂, 近藤 星, Fu Shanqi, 大野充昭, 古松毅之, 中田英二, 滝川正春, 服部高子, 久保田聡

    第95回日本生化学会 。、2022, 11, 9-11, 名古屋  2022.11.9 

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    Event date： 2022.11.9 - 2022.11.11

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  • C型レクチン受容体CD302による骨芽細胞の接着制御機構の解明。

    青山絵理子, 久保田聡, 滝川正春

    第95回日本生化学会 。、2022, 11, 9-11, 名古屋  2022.11 

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    Event date： 2022.11.9 - 2022.11.11

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  • DO NOT OVERWORK: CCN3 FOR LIFE IN CARTILAGE. Invited International conference

    Kubota S, Kawaki, H, Perbal, B, Takigawa, M, Kawata, K, Hattori T, Nishida, T

    2022.10.20 

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    Event date： 2022.10.20 - 2022.10.24

    Presentation type：Symposium, workshop panel (nominated)  

    Venue：Nice  

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  • S-アデノシルメチオニンはポリアミン産生だけでなく増殖因子の遺伝子発現を促進することによって軟骨細胞分化を促進する。

    ホアンディン ロック, 青山絵理子, 久保田聡, 窪木拓男, 滝川正春

    第64回 歯科基礎医学会  2022.9 

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    Event date： 2022.9.17 - 2022.9.19

    Language：English   Presentation type：Oral presentation (general)  

    Venue：徳島  

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  • CCN6はSmad1/5/8のリン酸化を阻害してBMP2促進性の口腔がん細胞の上皮間葉転換を抑制する。

    芳地浩彰, 西田 崇, 滝川正春, 久保田聡

    第64回 歯科基礎医学会  2022.9 

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    Event date： 2022.9.17 - 2022.9.19

    Presentation type：Oral presentation (general)  

    Venue：徳島  

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  • 線維化を制御するPU.1発現に対する核移行したCCN2の作用。

    西田 崇, 滝川正春, 久保田聡

    第64回 歯科基礎医学会  2022.9 

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    Event date： 2022.9.17 - 2022.9.19

    Presentation type：Oral presentation (general)  

    Venue：徳島  

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  • 骨芽細胞におけるCD302の発現と機能

    青山絵理子, 久保田聡, 滝川正春

    第44回日本分子生物学会年会  2021.12 

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    Event date： 2021.12.1 - 2021.12.3

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  • フッ化ナトリウムによるCCNファミリー遺伝子制御を介した歯肉線維化抑制作用の検討

    水川朋美、西田 崇、明石 翔、大杉綾花、大森一弘、中山真彰、高柴正悟、上岡 寛、滝川正春、久保田聡

    第42回岡山歯学会  2021.11.28 

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    Event date： 2021.11.28

  • メトホルミンによるUCA1を介した軟骨保護作用の解析

    近藤 星、服部高子、桑原実穂、Fu Shanqi、西田 崇、薬師寺翔太、吉岡洋祐、森谷徳文、 飯田征二、滝川正春、久保田聡

    第42回岡山歯学会  2021.11.28 

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    Event date： 2021.11.28

  • 口腔がん細胞のEMTと破骨細胞形成におけるCellular Communication Network factor 6 (CCN6)の抑制作用

    芳地浩彰、久保田聡、滝川正春、西田 崇

    第42回岡山歯学会  2021.11.28 

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    Event date： 2021.11.28

  • 軟骨細胞におけるRFX1を介したCCN3の発現制御機構の解明

    水川朋美、西田 崇、明石 翔、河田かずみ、菊池 菫、川木晴美、滝川正春、上岡 寛、久保田聡

    第94回日本生化学会大会 

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    Event date： 2021.11.3 - 2021.11.5

  • 近藤 星、服部高子、桑原実穂、Fu Shanqi、西田 崇、吉岡洋祐、森谷徳文、飯田征二、滝川正春、久保田聡

    メトホルミンのUCA1誘導および軟骨細胞分化促進作用

    第94回日本生化学会大会  2021.11.3 

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    Event date： 2021.11.3

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  • 変形性肩関節症とCCN3発現上昇の相関について

    廣瀬一樹、中田英二、服部高子、鉄永智紀、山田和希、佐藤嘉洋、桑原実穂、滝川正春、久保田聡、尾崎敏文

    第36回日本整形外科学会基礎学術集会 

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    Event date： 2021.10.14 - 2021.10.15

  • CCN6の破骨細胞形成における阻害作用 第39回日本骨代謝学会

    西田 崇, 芳地浩彰, 青山絵理子, 滝川正春, 久保田聡

    第39回日本骨代謝学会  2021.10.8 

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    Event date： 2021.10.8

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  • Hoang Dinh, L., Aoyama, E., Kubota, S., Kuboki, T., Takigawa, M

    2021.10.8 

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    Event date： 2021.10.8

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  • 変形性肩関節症モデルとしてのCCN3過剰発現マウス

    廣瀬一樹, 中田英二, 服部高子, 鉄永智紀, 山田和希, 佐藤嘉洋, 桑原実穂, 滝川正春, 久保田聡, 尾崎敏文

    第39回日本骨代謝学会  2021.10.8 

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    Event date： 2021.10.8

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  • 桑原美穂、近藤 星、Fu Shanqi.、大野充昭、古松毅之、中田英二、滝川正春、久保田 聡、服部高子

    CCN, は関節軟骨の加齢性変性を促進する

    第39回日本骨代謝学会  2021.10.8 

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    Event date： 2021.10.8

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  • 軟骨細解糖阻害剤NaFの線維化抑制効果とCCNファミリー遺伝子の関与

    回日本生化学会, 中国, 四国支部例会

    2021.9.10 

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    Event date： 2021.9.10 - 2021.9.11

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  • CCN2、CCN3とPDGFRLの軟骨細胞における生物学的作用へのHippo pathwayの関与

    河田かずみ, 青山絵理子, 滝川正春, 久保田聡

    第62回日本生化学会 中国・四国支部例会  2021.9.10 

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    Event date： 2021.9.10 - 2021.9.11

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  • non-coding RNAを介したメトホルミンの抗線維化作用の解析

    近藤 星, 服部高子, 桑原実穂, Fu Shanqi, 西田 崇, 吉岡洋祐, 森谷徳文, 飯田征二, 滝川正春, 久保田聡

    第75回日本口腔科学会  2021.5.12 

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    Event date： 2021.5.12 - 2021.5.14

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  • 軟骨細胞老化促進因子としてのCCN3

    桑原実穂, 武内聡子, 近藤 星, Fu Shanqi, 大野充昭, 古松毅之, 中田英二, 滝川正春, 久保田聡, 服部高子

    第33回日本軟骨代謝学会  2021.3.26 

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    Event date： 2021.3.26 - 2021.3.27

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  • 軟骨細胞における解糖系によるCCN3遺伝子発現制御メカニズム

    水川朋美, 西田 崇, 明石 翔, 上岡 寛, 滝川正春, 久保田聡

    第33回日本軟骨代謝学会  2021.3.26 

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    Event date： 2021.3.26 - 2021.3.27

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  • Regulation of CCN3 gene expression by glycolytic activity in chondrocytes.

    Mizukawa T, Nishida T, Akashi S, Kamioka H, Takigawa M, Kubota S

    The 9th International Orthodontic Congress 

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    Event date： 2020.10.4 - 2020.10.7

    Language：English   Presentation type：Oral presentation (general)  

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  • 軟骨細胞は加齢にともなってCCN3を高発現し、その過剰発現は軟骨加齢を促進する。

    桑原実穂, 武内聡子, 近藤 星, Fu, S, 大野充昭, 古松毅之, 中田英二, 滝川正春, 久保田聡, 服部高子

    第42回日本分子生物学学会  2019.12.5 

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    Event date： 2019.12.3 - 2019.12.6

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  • Role of interaction between CCN2 and Rab14 in vesicle trafficking in chondrocytes novel intracellular function of CCN2 International conference

    Hoshijima, M, Hattori, T, Aoyama, E, Nishida, T, Kubota, S, Kamioka, H, Takigawa M

    Eight International Workishop on the CCN Family of Genes  2015 

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    Event date： 2015.11.3 - 2015.11.8

    Presentation type：Symposium, workshop panel (nominated)  

    Venue：Nice  

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  • Induction of CCN2 by low-intensity pulsed ultrasound (LIPUS) in cultured chondrocytes and its biological significance. International conference

    Nishida, T, Kubota, S, Aoyama, E, Yamanaka, N, Lyons, K. M, Takigawa, M

    Eight International Workshop on the CCN Family of Genes, 

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    Event date： 2015.11.3 - 2015.11.8

    Presentation type：Symposium, workshop panel (nominated)  

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  • Regenerative effects of CCN2 independent modules and CCN3 on articular chondrocytes/cartilage. International conference

    Takigawa, M, Abd El Kader, T, Janune, D, Aoyama, E, Nishida, T, Hattori, T, Hara, E. S, One, M, Tabata, Y, Kuboki, T, Kubota, S

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    Event date： 2015.11.3

    Venue：Saint-Malo  

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  • Intraflagellar transport protein 88による象牙芽前駆細胞増殖制御機構へのCCNsの関与の可能性。

    河田かずみ, 青山絵理子, 滝川正春, 久保田聡

    第15回日本CCNファミリー研究会  2024.8.31  日本CCNファミリー研究会(代表世話人：滝川正春）

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  • Sアデノシルメチオニンによるポリアミン合成経路を介した軟骨細胞分化制御機構の解明

    青山絵理子, Hoang Dinh Loc, 日浅未来, 表 弘志, 久保田聡, 窪木拓男, 滝川正春

    第15回日本CCNファミリー研究会  2024.8.31  日本CCNファミリー研究会(代表世話人：滝川正春）

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    Venue：岡山  

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  • Low-Intensity Pulsed Ultrasound (LIPUS) enhances the osteogenic differentiation of mesenchymal stem cells in cooperation with Bone Morphogenetic Protein-2 (BMP-2).

    Paing, H.M, Nishida, T, Takigawa, M, Takuo Kuboki, T, Kubota, S

    第15回日本CCNファミリー研究会  2024.8.31  日本CCNファミリー研究会(代表世話人：滝川正春）

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    Venue：岡山  

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  • 核内CCN2は転写共役因子として関節軟骨の維持に作用する。

    西田 崇, 長尾由里香, 滝川正春, 久保田聡

    第15回日本CCNファミリー研究会  2024.8.31  日本CCNファミリー研究会(代表世話人：滝川正春）

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    Venue：岡山  

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  • 軟骨細胞におけるCCN2の核移行の意義。

    西田 崇, 滝川正春, 久保田聡

    第14回日本CCNファミリー研究会  2023.9.2 

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  • CCN6はBMP2による口腔がん細胞の上皮・間葉転換をコントロールする。

    芳地浩彰, 久保田聡, 滝川正春, 西田 崇

    第14回日本CCNファミリー研究会  2023.9.2 

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    Venue：岡山  

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  • 軟骨細胞増殖・分化におけるHippo pathwayを介したCCNsとPDGFRLの関与。

    河田かずみ, 青山絵理子, 滝川正春, 久保田聡

    第14回日本CCNファミリー研究会  2023.9.2 

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    Venue：岡山  

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  • 軟骨細胞におけるCCN2由来circRNAの発現とその機能の検証。

    加藤壮真, 河田かずみ, 西田 崇, 水川朋美, 滝川正春, 飯田征二, 久保田聡

    第14回日本CCNファミリー研究会  2023.9.2 

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    Venue：岡山  

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  • S-アデノシルメチオニンによるポリアミン産生および成長因子発現を介した軟骨細胞分化の制御。

    Hoang, L, Aoyama, E, Hiasa, M, Omote, H, Kubota, S, Kuboki, T, Takigawa, M

    第95回日本生化学会 。、2022, 11, 9-11, 名古屋  2022.11.9 

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  • 変形性股関節症とCCN3発現の相関

    廣瀬一樹, 中田英二, 鉄永智紀, 山田和希, 佐藤嘉洋, 小浦卓, 服部高子, 桑原美穂, 滝川正春, 久保田聡, 尾﨑敏文

    第37回日本整形外科基礎学術集会  2022.10 

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  • 口腔がん細胞の上皮間葉転換に与えるCCN6の抑制作用。

    芳地浩彰, 西田 崇, 滝川正春, 久保田聡

    第13回日本CCNファミリー研究会  2022.9.3 

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  • 筋線維芽細胞分化における細胞内CCN2の作用

    西田 崇, 辰川ひなた, 滝川正春, 久保田聡

    第13回日本CCNファミリー研究会  2022.9.3 

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  • S-adenosylmethionine can promote polyamine production and growth factor genes expression thereby regulating chondrocytic differentiation

    Hoang Dinh, L, Aoyama, E, Hiasa, M, Omote, H, Kubota, S, Kuboki, T, Takigawa, M

    2022.9.3 

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  • GDF5とCCN2との結合が軟骨細胞に及ぼす影響の検討

    東原直裕, 青山絵理子, 古松毅之, 久保田聡, 尾﨑敏文, 滝川正春

    第13回日本CCNファミリー研究会  2022.9.3 

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  • CCN

    2022.9.3 

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  • 軟骨細胞におけるCCN2由来環状RNAの発現とその機能の探索

    加藤壮真, 河田かずみ, 西田 崇, 水川朋美, 飯田征二, 久保田聡

    第13回日本CCNファミリー研究会  2022.9.3 

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  • メトホルミンの軟骨細胞におけるlong non-coding RNA, UCA1およびCCN2の発現制御と代謝における意義。

    近藤 星, 服部高子, 桑原実穂, Fu Shanqi, 西田 崇, 薬師寺翔太, 吉岡洋祐, 森谷徳文, 飯田征二, 滝川正春, 久保田聡

    第13回日本CCNファミリー研究会  2022.9.3 

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  • 象牙芽前駆細胞におけるIFT88の機能 -CCNsの関与の可能性-。

    河田かずみ, 成田啓之, 青山絵理子, 北村知昭, 西原達次, 滝川正春, 竹田 扇, 久保田聡

    第13回日本CCNファミリー研究会  2022.9.3 

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  • Intragellar transport protein 88による象牙芽前駆細胞増殖制御機構

    河田かずみ, 青山絵理子, 久保田聡

    第64回 歯科基礎医学会  2022.9 

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  • CCN2

    回 歯科基礎医学会

    2022.9 

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  • 軟骨細胞におけるCCN2由来環状RNAの発現。

    加藤壮真, 河田かずみ, 西田 崇, 久保田聡

    第64回 歯科基礎医学会  2022.9 

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  • 線維化を制御するPU.1発現に対する核移行したCCN2の作用

    西田 崇, 滝川正春, 久保田聡

    第64回 歯科基礎医学会  2022.9 

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  • CCN6のBMP2とRANKLとの結合を介したEMT及び破骨細胞形成に対する抑制作用

    芳地浩彰, 西田 崇, 滝川正春, 久保田聡

    第40回日本骨代謝学会  2022.7.22 

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  • 変形性関節症とCCN3発現の相関

    廣瀬一樹, 服部高子, 桑原実穂, 滝川正春, 中田英二, 鉄永智紀, 山田和希, 佐藤嘉洋, 小浦 卓, 尾崎敏文, 久保田聡

    第40回日本骨代謝学会  2022.7 

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  • 変形性股関節症とCCN3発現の相関

    廣瀬一樹, 服部高子, 滝川正春, 中田英二, 鉄永智紀, 山田和希, 佐藤嘉洋, 小浦卓, 尾﨑敏文, 久保田聡

    第42回日本骨形態計測学会  2022.6 

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  • 軟骨代謝研究の過去40年と将来展望 Invited

    滝川正春

    第34回日本軟骨代謝学会  2022.2.18 

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  • 軟骨細胞における転写因子RFX1を介したCCN3の発現制御機構とその役割

    水川朋美, 西田 崇, 明石 翔, 河田かずみ, 菊池 菫, 川木晴美, 滝川正春, 上岡 寛, 久保田聡

    第34回日本軟骨代謝学会  2022.2 

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  • 変形性股関節症とCCN3発現の相関

    廣瀬一樹, 中田英二, 服部高子, 鉄永智紀, 山田和希, 佐藤嘉洋, 桑原実穂, 滝川正春, 久保田聡, 尾崎敏文

    第34回日本軟骨代謝学会  2022.2 

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  • 軟骨細胞におけるGDF5とCCN2との結合の意義

    東原直裕, 青山絵理子, 古松毅之, 久保田聡, 尾崎敏文, 滝川正春

    第34回日本軟骨代謝学会  2022.2 

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  • メトホルミンによる非コードRNA誘導と軟骨細胞分化促進作用

    近藤 星, 服部高子, 桑原実穂, Fu Shanqi, 西田 崇, 薬師寺翔太, 吉岡洋祐, 森谷徳文, 飯田征二, 滝川正春, 久保田聡

    第34回日本軟骨代謝学会  2022.2 

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  • メトホルミンの軟骨細胞におけるUCA1誘導をともなった分化促進作用

    近藤 星, 服部高子, 桑原実穂, Fu Shanqi, 西田 崇, 吉岡洋祐, 森谷徳文, 飯田征二, 滝川正春, 久保田聡

    第44回日本分子生物学会年会  2021.12 

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  • 軟骨細胞におけるCCN2、CCN3とPDGFRLの生物学的作用におけるHippo pathwayの関与

    河田かずみ, 青山絵理子, 滝川正春, 久保田聡

    第44回日本分子生物学会年会  2021.12 

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  • 青山絵理子、久保田聡、滝川正春

    C型レクチン様受容体, 骨芽細胞における発現と機能, 回日本生化学会大会

    第94回日本生化学会大会  2021.11.3 

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  • 軟骨細胞におけるRFX1を介したCCN3の発現制御機構の解明

    水川朋美, 西田 崇, 明石 翔, 河田かずみ, 菊池 菫, 川木晴美, 滝川正春, 上岡 寛, 久保田聡

    第94回日本生化学会大会  2021.11.3 

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  • Cellular Communication Network factor 6 (CCN6)のEMT 及び破骨細胞形成に対する抑制作用

    芳地浩彰, 西田 崇, 滝川正春, 久保田聡

    第12回日本CCNファミリー研究会  2021.9.4 

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  • CCN3とPDGFRLの軟骨細胞への作用におけるHippo pathwayの関与

    河田かずみ, 青山絵理子, 滝川正春, 久保田聡

    第12回日本CCNファミリー研究会  2021.9.4 

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  • 軟骨細胞でのRFX1によるCCNファミリータンパク質3遺伝子制御メカニズム

    水川朋美, 西田 崇, 明石 翔, 河田かずみ, 菊池 菫, 川木晴美, 滝川正春, 上岡 寛, 久保田聡

    第12回日本CCNファミリー研究会  2021.9.4 

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  • Chondrocyte differentiation is positively regulated by S-adenosyl- methionine via polyamine biosynthesis

    回日本CCNファミリー研究会

    2021.9.4 

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  • メトホルミンの軟骨細胞分化促進作用におけるUCA1とCCN2の役割

    近藤 星, 服部高子, 桑原実穂, Fu Shanqi, 西田 崇, 吉岡洋祐, 森谷徳文, 飯田征二, 滝川正春, 久保田聡

    第12回日本CCNファミリー研究会  2021.9.4 

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  • ヒトiPS細胞由来神経前駆細胞の神経分化におけるCCN経路の発見

    葛原 隆, 庄司正樹, 関 真秀, 上田雅子, 西岡 恵, 港 洋希, 青山絵理子, 原田研一, 久保美和, 福山愛保, 鈴木 穣, 滝川正春

    第12回日本CCNファミリー研究会  2021.9.4 

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  • 成体神経筋接合部でのCCNファミリーの役割

    大河原美静, 服部高子, 久保田聡, 伊藤美佳子, 増田章男, 滝川正春, Karen M. Lyons, 大野欽司, 成体神経筋接合部でのCCNファミリーの役割

    第12回日本CCNファミリー研究会  2021.9.4 

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  • 軟骨細胞におけるエネルギー代謝不全時でのCCN3増産システムの解明

    水川朋美, 西田 崇, 明石 翔, 上岡 寛, 滝川正春, 久保田聡

    第38回日本骨代謝学会学術集会  2020.10.10 

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  • LIPUSによる脂肪細胞分化の抑制と骨芽細胞分化への影響

    西田 崇, 滝川正春, 久保田聡

    第38回日本骨代謝学会学術集会  2020.10.10 

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  • S-アデノシルメチオニンによるポリアミン合成促進を介した軟骨細胞の分化促進作用

    棚井あいり, 青山絵理子, 久保田聡, 滝川正春

    第52回日本結合組織学会  2020.9.19 

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  • S-アデノシルメチオニンはポリアミン合成経路を介して軟骨細胞の増殖および基質合成を促進する。

    青山絵理子, 久保田聡, 滝川正春

    第62回歯科基礎医学会  2020.9.12 

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  • CCN2の核移行による線維化の制御

    西田 崇, 滝川正春, 久保田聡

    第62回歯科基礎医学会  2020.9.12 

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  • 軟骨細胞での解糖活性による;遺伝子の発現調節

    水川朋美, 西田 崇, 明石 翔, 掘 綾花, 高柴正悟, 上岡 寛, 滝川正春, 久保田聡

    第61回日本生化学会;中国;四国支部例会  2020.5.23 

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  • Mechanism of enhancement by S-adenosylmethionine;SAM) on chondrocyte proliferation;differentiation;possible involvement of polyamine synthesis

    Tanai A, Aoyama E, Kubota S, Takigawa M

    2020.5.23 

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  • 軟骨細胞の分化過程におけるCCN2の発現変動の意義

    村瀬友里香, 青山絵理子, 鈴木康弘, 佐々木朗, 久保田聡, 佐藤靖史, 滝川正春

    第42回日本分子生物学学会  2019.12.6 

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  • 癌抑制遺伝子PDGFRLはCCN2、CCN3のデコイ受容体として軟骨細胞増殖と分化を制御する

    河田 かずみ, 久保田 聡, 滝川正春

    第37回日本骨代謝学会学術集会  2019.10.14 

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  • Angiotensin IIによる軟骨変性作用とそのCCN2による制御機構

    西田 崇, 滝川正春, 久保田聡

    第37回日本骨代謝学会学術集会  2019.10.13 

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  • 低出力パルス超音波（LIPUS）の半月板修復効果とその作用機序 -CCN2/CTGFの関与

    青山絵理子, 西田 崇, 久保田聡, 滝川正春

    第61回歯科基礎医学会学術大会  2019.10.13 

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  • 脂肪細胞分化に対する低出力パルス超音波(LIPUS)の抑制メカニズムの解明

    橋谷智子, 西田 崇, 長尾有里香, 滝川正春, 久保田聡

    第61回歯科基礎医学会学術大会  2019.10.12 

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  • 破骨細胞分化過程における低出力超音波パルスの細胞死誘導作用とそのメカニズムの解析

    青山絵理子, 久保田聡, 滝川正春

    第61回歯科基礎医学会学術大会  2019.10.12 

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  • 低出力超音波パルス刺激による破骨細胞前駆細胞のアポトーシス誘導とそのメカニズム

    青山絵理子, 久保田聡, 山中信康, 滝川正春

    第92回日本生化学会大会  2019.9.19 

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  • 低出力性パルス超音波(LIPUS)による脂肪細胞分化の多面的抑制機構

    西田 崇, 長尾有里香, 橋谷智子, 山中信康, 滝川正春, 久保田聡

    第92回日本生化学会大会  2019.9.18 

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  • 破骨細胞に対する低周波超音波パルスの分化抑制作用とその機序の解明

    青山絵理子, 久保田聡, 山中信康, 滝川正春

    第11回日本CCNファミリー研究会  2019.8.31 

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  • 低出力性パルス超音波(LIPUS)による脂肪細胞分化の抑制機構の解明

    西田 崇, 長尾有里香, 橋谷智子, 山中信康, 滝川正春, 久保田聡

    第11回日本CCNファミリー研究会  2019.8.31 

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  • Tsukushiと脳疾患発症の連関

    太田訓正, 青山絵理子, Shah Adil Ishtiyaq Ahmad、Mohammad, Badrul Anam, 伊藤尚文, 久保田聡, 滝川正春

    第11回日本CCNファミリー研究会  2019.8.31 

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  • 好転異性癌細胞で高発現するMMP3が有するCtgf/Ccn2発現調節機能と細胞外小胞の関連

    奥舎有加, 江口傑徳, タハ・エマン、チャン・チェン・マン, 十川千春, 青山絵理子, 滝川正春, 岡元邦彰

    第11回日本CCNファミリー研究会  2019.8.31 

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  • 癌抑制遺伝子PDGFRLはCCN2、CCN3による軟骨細胞増殖と分化の制御を抑制する

    河田かずみ, 久保田聡, 滝川正春

    第11回日本CCNファミリー研究会  2019.8.31 

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  • 軟骨細胞におけるAngiotensin IIの産生調節とその作用

    西田 崇, 明石 翔, 滝川正春, 久保田聡

    第32回日本軟骨代謝学会  2019.3.2 

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  • 軟骨細胞におけるCCNファミリー遺伝子のエネルギー代謝による制御

    明石 翔, 西田 崇, El-Seoudi A, 滝川正春, 飯田征二, 久保田聡

    第32回日本軟骨代謝学会  2019.3.1 

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  • CCN2 と Rab14 の相互作用が骨・軟骨細胞の小胞輸送に及ぼす役割 〜軟骨分化促進因子 CCN2 の新たな細胞内機能〜

    星島光博, 服部高子, 青山絵理子, 西田 崇, 久保田聡, 上岡 寛, 滝川 正春

    第60回歯科基礎医学会学術大会  2018.9.7 

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  • 江口傑徳、小野喜章、奥舎有加、十川千春、内部健太、中野啓介、奥井達雄、滝川正春、岡元邦彰：癌の治療抵抗性と転移におけるHSP90およびMM３の役割

    江口傑徳, 小野喜章, 奥舎有加, 十川千春, 内部健太, 中野啓介, 奥井達雄, 滝川正春, 岡元邦彰

    第60回歯科基礎医学会  2018.9.6 

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  • ヒト軟骨細胞分化におけるUCA1長鎖非コードRNAの役割

    第31回日本軟骨代謝学会  2018 

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  • 低出力超音波パルスによる破骨細胞前駆細胞の成熟抑制メカニズムの解明

    第41回日本分子生物学会年会  2018 

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  • Effect of Fibroblast growth factor 1 (FGF-1) on connective tissue growth factor (CCN2/CTGF) gene expression in chondrocytic cells and its possible role in steoarthritis

    第39回岡山歯学会  2018 

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  • Effect of Fibroblast Growth Factor (FGF-1) on CCN2 Gene Expression in Chondrocytic Cells

    第41回日本分子生物学会年会  2018 

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  • CCN2-VASH1-SOD2 axisによる軟骨細胞終末分化における細胞死の制御

    第41回日本分子生物学会年会  2018 

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  • 軟骨細胞におけるCCN3遺伝子の糖代謝を介した制御

    第91回日本生化学会  2018 

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  • LIPUSが半月板修復に与える影響

    第33回日本整形外科学会基礎学術集会  2018 

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  • 軟骨細胞におけるCCN3遺伝子の糖代謝を介した制御

    第10回日本CCNファミリー研究会  2018 

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  • 低出力パルス超音波（LIPUS）が半月板に与える影響

    第10回日本CCNファミリー研究会  2018 

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  • 低出力性パルス超音波(LIPUS)による脂肪細胞分化抑制機構の解明

    第60回歯科基礎医学会学術大会  2018 

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  • 軟骨細胞によるCCN2とMMP9産生に対するアンジオテンシンIIの作用

    第10回日本CCNファミリー研究会  2018 

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  • 低出力超音波パルスによる破骨細胞分化の抑制とそのメカニズムの解明

    第60回歯科基礎医学会学術大会  2018 

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  • 培養軟骨細胞においてアンジオテンシンⅡはCCN2とMMP9の産生を制御する

    第60回歯科基礎医学会学術大会  2018 

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  • 癌の治療抵抗性と転移における HSP90 および MMP3 の役割

    第60回歯科基礎医学会学術大会  2018 

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  • 軟骨細胞におけるCCN3遺伝子の糖代謝を介した制御

    第36回日本骨代謝学会  2018 

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  • 局所性Renin-Angiotensin System を介したAngiotensin IIが軟骨基質産生に与える影響

    第36回日本骨代謝学会  2018 

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  • 低出力超音波パルスによって誘導される破骨細胞前駆細胞の細胞死とTAZの活性化

    第36回日本骨代謝学会  2018 

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  • 培養軟骨細胞におけるCCN2及びMMP9の産生に対するアンジオテンシンIIの作用

    第31回日本軟骨代謝学会  2018 

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  • 軟骨細胞におけるCCN3遺伝子の糖代謝を介した制御

    第31回日本軟骨代謝学会  2018 

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  • FGF-1 affects the expression of MMP-13 and CCN2 in chondrocytes: possible role in osteoarthritis

    第31回日本軟骨代謝学会  2018 

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  • LIPUSが半月板に与える効果

    第50回日本結合組織学会  2018 

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  • 象牙芽細胞に対するグルココルチコイドの作用におけるIFT88の役割

    第59回日本生化学会 中国・四国支部例会  2018 

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  • 軟骨細胞、骨芽細胞分化にUCA1長鎖ノンコーディングRNAが与える影響

    第36回日本骨代謝学会  2018 

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  • 低出力パルス超音波（LIPUS）が半月板に与える影響

    第36回日本骨代謝学会  2018 

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  • 半月板に対する低出力パルス超音波（LIPUS）の効果

    第31回日本軟骨代謝学会  2018 

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  • CCN2-VASH1-SOD2 axisを介した内軟骨性骨化調節機構

    第31回日本軟骨代謝学会  2018 

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  • Mechanism of the catabolic effects of Fibroblast Growth Factor (FGF-1) on chondrocytes and its possible role in Osteoarthritis

    第30回日本軟骨代謝学会  2017 

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  • 低出力パルス超音波（LIPUS）によりCCN2の発現・産生は増加する

    2017年度生命科学系学会合同年次大会 第40回日本分子生物学会 第90回日本生化学会大会  2017 

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  • 低出力超音波パルス（LIPUS）刺激による破骨細胞形成の抑制

    2017年度生命科学系学会合同年次大会 第40回日本分子生物学会 第90回日本生化学会大会  2017 

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  • 細胞外情報を統合するCCNファミリー遺伝子の糖代謝を介した制御

    2017年度生命科学系学会合同年次大会 第40回日本分子生物学会 第90回日本生化学会大会  2017 

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  • 内軟骨性骨化におけるvasohibin-1 (VASH1)の発現とその意義

    2017年度生命科学系学会合同年次大会 第40回日本分子生物学会 第90回日本生化学会大会  2017 

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  • CCN2とRab14の相互作用が骨・軟骨細胞の小胞輸送に及ぼす役割

    2017年度生命科学系学会合同年次大会 第40回日本分子生物学会 第90回日本生化学会大会  2017 

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  • DEX刺激によるIFT88を介した細胞増殖抑制とCcn4, 5発現抑制

    第38回岡山歯学会  2017 

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  • Catabolic effects of FGF-1 on chondrocytes with reduced CCN2 production and its possible role in osteoarthritis

    第9回日本CCNファミリー研究会  2017 

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  • 軟骨細胞におけるセロトニンによるCCN2の産生制御機構の解明

    第9回日本CCNファミリー研究会  2017 

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  • CCN2結合因子GDF5の軟骨細胞における作用の解明

    第9回日本CCNファミリー研究会  2017 

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  • MMP3はヘテロクロマチンタンパク質HP1と相互作用してHSP遺伝子群を制御する

    第9回日本CCNファミリー研究会  2017 

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  • 老齢期の破骨細胞形成における骨細胞由来のCCN2の役割

    第59回歯科基礎医学会  2017 

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  • CCN2によるVASH1を介した内軟骨性骨化調節機構の解明

    第9回日本CCNファミリー研究会  2017 

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  • GDF5との結合を介したCCN2の軟骨分化促進作用

    第59回歯科基礎医学会  2017 

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  • 細胞内におけるマトリックスメタロプロテアーゼ (MMP)の役割

    第59回歯科基礎医学会  2017 

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  • 軟骨細胞におけるCCN3遺伝子の糖代謝を介した制御

    第38回岡山歯学会  2017 

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  • LIPUSにより半月板でのCCN2の発現・産生は増加する

    第36回日本運動器移植・再生医学研究会  2017 

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  • 細胞外情報を統合するCCNファミリー遺伝子の糖代謝を介した制御

    第58回日本生化学会中国・四国支部例会  2017 

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  • 老齢マウスにおいて骨細胞由来CCN2は骨髄細胞由来CCN2よりも破骨細胞形成と骨リモデリングに重要である

    第35回日本骨代謝学会  2017 

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  • 半月板におけるCCN2, CCN3に与える低出力パルス超音波(LIPUS)の効果

    第49回日本結合組織学会学術大会  2017 

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  • 関節•成長板軟骨細胞におけるセロトニン (5-HT)によるCCN2産生の差別的制御メカニズム

    第35回日本骨代謝学会  2017 

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  • 軟骨細胞分化に関わる長鎖非コードRNAの骨形成における役割

    第35回日本骨代謝学会  2017 

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  • Vasohibin-1 (VASH1)による内軟骨性骨化とCCN2の関与

    第35回日本骨代謝学会  2017 

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  • 低出力パルス超音波（LIPUS）が半月板中のCCN2, CCN3に与える効果

    第35回日本骨代謝学会  2017 

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  • 培養軟骨細胞のCCN2産生における低出力性パルス超音波(LIPUS)処置の作用メカニズムの解明

    第9回日本CCNファミリー研究会  2017 

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  • Catabolic effects of FGF-1 on chondrocytes with reduced CCN2 production that promotes cartilage regeneration: Possible role in osteoarthritis

    第35回日本骨代謝学会  2017 

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  • 細胞外情報を統合するCCNファミリー遺伝子の糖代謝を介した制御

    第9回日本CCNファミリー研究会  2017 

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  • 軟骨細胞分化に関わる長鎖ノンコーディングRNAの解析

    第30回日本軟骨代謝学会  2017 

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  • 骨格形成における低密度リポたんぱく質受容体関連たんぱく質1（LRP１）の役割

    第30回日本軟骨代謝学会  2017 

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  • 軟骨細胞のCCN2産生に対するセロトニン(5-HT)の制御機構の解明

    第30回日本軟骨代謝学会  2017 

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  • 膝半月板におけるCCN2, CCN3に与える低出力パルス超音波(LIPUS)の効果

    第30回日本軟骨代謝学会  2017 

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  • 骨のリモデリング期のCCN2欠損は骨細胞由来の破骨細胞形成を抑制する

    第8回日本CCNファミリー研究会  2016 

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  • Effects of fibroblast growth factor 1 (FGF1) on chondrocytes and its possible role in osteoarthritis

    第89回日本生化学会  2016 

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  • CCN2結合因子CD302の破骨細胞機能制御作用

    第8回日本CCNファミリー研究会  2016 

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  • 軟骨細胞におけるCCN2産生に対するセロトニン(5-HT)の作用

    第37回岡山歯学会  2016 

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  • CCN2結合因子CD302による破骨細胞成熟促進作用とその機序の解析

    第89回日本生化学会  2016 

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  • 破骨細胞成熟過程におけるCD302の機能とCCN2との関わり

    第39回日本分子生物学会  2016 

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  • セロトニン(5-HT)による軟骨細胞におけるCCN2産生の作用機構の解明

    第34回日本骨代謝学会学術集会 第3回アジア太平洋骨代謝学会議  2016 

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  • 格形成における低密度リポタンパク受容体関連タンパク1（LRP１）の役割

    第34回日本骨代謝学会学術集会 第3回アジア太平洋骨代謝学会議  2016 

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  • 軟骨細胞形質に関わる長鎖非コードRNAの探索

    第34回日本骨代謝学会学術集会 第3回アジア太平洋骨代謝学会議  2016 

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  • 破骨細胞におけるCCN2結合性アクチン骨格制御因子CD302の作用機序の解明

    第58回歯科基礎医学会学術大会  2016 

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  • タモキシフェン誘導性CCN2欠損マウス由来の骨細胞様細胞の破骨細胞形成能

    第58回歯科基礎医学会学術大会  2016 

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  • 膝半月板細胞におけるCCN2、CCN3発現量に与える低出力超音波(LIPUS)の効果

    第8回日本CCNファミリー研究会  2016 

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  • CCN2による軟骨細胞増殖・分化促進に対する癌抑制遺伝子PDGFR-like (PDGFRL)の効果

    第8回日本CCNファミリー研究会  2016 

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  • 軟骨細胞におけるセロトニン（5−HT）のCCN2産生促進機構の解明

    第8回日本CCNファミリー研究会  2016 

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  • Mechanism of the catabolic effects of Fibroblast Growth Factor (FGF-1) on chondrocytes and its role in CCN2 regulation

    第8回日本CCNファミリー研究会  2016 

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  • CCN2結合因子DCL-1/CD302による破骨細胞の成熟促進作用の機構解明

    第34回日本骨代謝学会学術集会 第3回アジア太平洋骨代謝学会議  2016 

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  • 軟骨細胞分化における癌抑制遺伝子PDGFR-like (PDGFRL)の役割

    第29回日本軟骨代謝学会  2016 

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  • 軟骨細胞形成を支える長鎖非コードRNA

    第29回日本軟骨代謝学会  2016 

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  • 血小板に含まれるCCNファミリータンパク質の解析と軟骨再生への応用

    第29回日本軟骨代謝学会  2016 

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  • CCN2産生を誘導するセロトニンの軟骨細胞内でのシグナル伝達機構の解析

    第29回日本軟骨代謝学会  2016 

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  • Investigation on long non-coding RNAs that are associated with chondrocytic phenotype

    RNA2016  2016 

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  • Role of CCN2/CTGF-related CD302 in osteoclast maturation

    94th IADR General Session  2016 

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  • 骨細胞様細胞におけるCCN2の欠損は破骨細胞形成を抑制する

    第34回日本骨代謝学会学術集会 第3回アジア太平洋骨代謝学会議  2016 

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  • E6-AP/UBE3A Protein, a Ubiquitin Ligase toward SOX9 Protein is essential to endochondral ossificati

    Gordon Research Conferences Cartilage Biology & Pathology  2015 

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  • CCN2とRab14の相互作用が軟骨細胞の小胞輸送に及ぼす役割 〜軟骨分化促進因子CCN2の新たな細胞内機能〜

    第57回歯科基礎医学会  2015 

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  • CCN2の新たな細胞内機能：CCN2 とRab14の相互作用が軟骨細胞の小胞輸送に及ぼす役割

    第7回日本CCNファミリー研究会  2015 

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  • Introducing CCN2 independent modules as a regenerative therapy for osteoarthritis and futher selecting the most suitable among them

    第7回日本CCNファミリー研究会  2015 

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  • CCN2による軟骨細胞アミノ酸代謝制御機構の解明

    第7回日本CCNファミリー研究会  2015 

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  • interaction of CCN2 with varied growth factors and cytokines involved in chondrocyte differentiation during endochondral ossification

    第7回日本CCNファミリー研究会  2015 

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  • Ccn4欠損マウスを用いた関節軟骨創傷治癒におけるCCN4の役割の解明

    第7回日本CCNファミリー研究会  2015 

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  • 破骨細胞形成を制御する骨細胞に与えるCCN2の作用

    第33回日本骨代謝学会  2015 

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  • 新たな破骨細胞制御因子DCL-1/CD302の作用機構の解明とCCN2との関連

    第33回日本骨代謝学会  2015 

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  • 関節軟骨におけるCCN3の新機能

    第33回日本骨代謝学会  2015 

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  • CCN2による軟骨細胞のアミノ酸代謝制御

    第33回日本骨代謝学会  2015 

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  • 巨核球および血小板に存在するCCNファミリータンパク質の存在様態とその由来

    第33回日本骨代謝学会  2015 

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  • 軟骨細胞アミノ酸代謝とCCN2

    第6回骨バイオサイエンス研究会  2015 

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  • 破骨細胞の成熟を制御する新規膜タンパク質CD302/DCL-1の機能とCCN2との結合

    第6回骨バイオサイエンス研究会  2015 

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  • CCNファミリー研究の歴史と最前線

    第33回日本骨代謝学会  2015 

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  • The combination of fluocinolone acetonide and TGF-b3 promotes strong chondrogenesis of hBMSCs for articular surface regeneration

    第6回骨バイオサイエンス研究会  2015 

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  • Among glucocorticoids fluocinolone acetonide is unique in potentiating TGF-b3-nediated chondrogensis of BMSCs and promoting articular cartilage repair

    第33回日本骨代謝学会  2015 

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  • 軟骨特異的CCN3過剰発現は内軟骨性骨化の遅延と関節変性を誘発する

    第33回日本骨代謝学会  2015 

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  • 骨軟骨再生因子CCN2の軟骨細胞アミノ酸代謝への影響

    第28回日本軟骨代謝学会  2015 

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  • CCN2とRab14の相互作用が軟骨細胞の小胞輸送に及ぼす役割

    第28回日本軟骨代謝学会  2015 

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  • 成熟破骨細胞の形成におけるCD302/DCL-1の新機能とCCN2との関連

    第1回日本骨免疫学会  2015 

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  • 破骨細胞分化における新規アクチン骨格制御因子としてのDCL-1/CD302の役割とCCN2との関連

    第57回歯科基礎医学会  2015 

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  • 軟骨細胞分化に与えるセロトニンの作用

    第28回日本軟骨代謝学会  2015 

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  • 骨細胞の作用を介した破骨細胞形成におけるCCN2の役割

    第38回分子生物学会年会・第88回生化学会大会合同大会BMB2016  2015 

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  • 成熟破骨細胞のアクチンリング形成におけるCD302の機能とCCN2による制御

    第38回分子生物学会年会・第88回生化学会大会合同大会BMB2015  2015 

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  • 関節軟骨におけるCCN3の新機能

    第7回日本CCNファミリー研究会  2015 

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  • CCN2によるTRAIL誘導性アポトーシス促進作用

    第7回日本CCNファミリー研究会  2015 

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  • CCN2は骨細胞に作用し、破骨細胞を正に制御する

    第7回日本CCNファミリー研究会  2015 

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  • CCN2は骨細胞を介して破骨細胞形成を制御する

    第57回歯科基礎医学会  2015 

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  • The Role of CCN2/CTGF/Hcs24 in Skeletal Growth, Maintenance and Regeneration.

    Takigawa M

    Invited Special Lecture at Institute of Biotechnology, University of Helsinki,  2014.5.22 

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    Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • 軟骨細胞での解糖活性によるCC;遺伝子の発現調節

    水川朋美, 西田 崇, 明石 翔, 掘 綾花, 高柴正悟, 上岡 寛, 滝川正春, 久保田聡

    第61回日本生化学会 中国・四国支部例会  2010.5.23 

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  • Suppression of BMP-2-induced osteogenic differentiation of hBMSCs by TNF-

    The International Association for Dental Research  2010 

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  • Role of the low-densitylipoprotein receptor-related protein 1 (LRP1) in CCN2 protein transportation in chondrocytes

    BMB2010 (第83回日本生化学会大会、第33回日本分子生物学会年会)  2010 

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  • 軟骨組織特異的CCN2/CTGF過剰発現による膝関節軟骨の加齢変性抑制効果

    BMB2010 (第83回日本生化学会大会、第33回日本分子生物学会年会)  2010 

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  • CCN2/CTGFはマトリリン-3と結合して軟骨マトリックス成分のネットワーク形成を促進する

    BMB2010 (第83回日本生化学会大会、第33回日本分子生物学会年会)  2010 

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  • The role of CCN2/CTGF binding to receptor activator of NF-κB (RANK) in the RANK-RANK ligand system

    BMB2010 (第83回日本生化学会大会、第33回日本分子生物学会年会)  2010 

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  • FGF2刺激による軟骨細胞増殖促進及びMMP13酵素活性上昇に与えるCCN2/CTGFの影響

    BMB2010 (第83回日本生化学会大会、第33回日本分子生物学会年会)  2010 

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  • CCN2/CTGF interacts with Matrilin-3 and enhances assembly of a cartilage matrix protein and filamentous network

    The 6th International Workshop on the CCN Family of Genes  2010 

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  • CCN2/CTGFのホモダイマー形成、およびCCN3/NOVとのヘテロダイマーの形成と、それらが軟骨細胞の基質合成に及ぼす役割

    BMB2010 (第83回日本生化学会大会、第33回日本分子生物学会年会)  2010 

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  • Screening of CCN2-binding peptides and its scientific utility

    The 6th International Workshop on the CCN Family of Genes  2010 

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  • Exportin-1によるCCN2/CTGFの核-細胞質間分子輸送とその生理的意義

    第52回歯科基礎医学会  2010 

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  • 軟骨細胞におけるFGF2機能の新規モジュレーターとしてのCCN2/CTGFの作用

    第52回歯科基礎医学会  2010 

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  • Cartilage-specific overexpression of CCN2/CTGF protects articular cartilage from age-related osteoarthritis-like changes

    The 6th International Workshop on the CCN Family of Genes  2010 

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  • ヒト前十字靱帯細胞におけるCTGF/CCN2の発現と周期的伸長負荷の効果

    第25回日本整形外科学会基礎学術集会  2010 

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  • Role of the Low-density lipoprotein receptor related protein 1 (LRP1) in CCN2/ Conncective tissue growth factor (CTGF) protein transportation in chondrocytes

    The 6th International Workshop on the CCN Family of Genes  2010 

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  • Chondrocyte-haemopoietic cell interaction that inducea CCN2 and its physiological significance. Multiple regulation of human CCN1 via the 3’UTR untranslated region and its biological significance

    The 6th International Workshop on the CCN Family of Genes  2010 

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  • CCN2/CTGF binds to fibroblast growth factor receptor 2 and modulates its signaling

    The 6th International Workshop on the CCN Family of Genes  2010 

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  • Expression and functional role of CCN3/Nov during articular cartilage development

    The 6th International Workshop on the CCN Family of Genes  2010 

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  • CCN1遺伝子転写後調節に関与するmiRNAの機能解析

    第52回歯科基礎医学会  2010 

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  • 軟骨組織特異的CCN2/CTGF過剰発現によりマウスの膝関節軟骨は加齢後もより正常に近い形質を維持する

    第52回歯科基礎医学会  2010 

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  • マイクロRNA181-aによる軟骨細胞形質の制御とCCN1の関与

    第28回日本骨代謝学会学術集会  2010 

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  • 低密度リポタンパク受容体関連タンパク-1（LRP1）による軟骨細胞でのタンパク質輸送

    第28回日本骨代謝学会学術集会  2010 

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  • CCN2/CTGFの核内移行とExportin-1による核—細胞質間分子輸送

    第28回日本骨代謝学会学術集会  2010 

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  • CCN2/CTGFとRANKの分子間相互作用も解析と骨代謝における意義

    第28回日本骨代謝学会学術集会  2010 

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  • Expression and functional role of NOV/CCN3 during articular cartilage development

    第28回日本骨代謝学会学術集会  2010 

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  • CCN2/CTGFのホモダイマー形成、およびCCN3/NOVとのヘテロダイマーの形成とそれらの軟骨細胞における生理作用

    第28回日本骨代謝学会学術集会  2010 

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  • CCN2/CTGFはマトリリン−３と結合して軟骨マトリックス成分のネットワーク形成を促進する

    第 42回日本結合組織学会学術大会・第57回マトリックス研究会大会合同学術集会  2010 

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  • 前十字靱帯細胞におけるCTGF/CCN2の発現と周期的伸張刺激負荷の効果

    第 42回日本結合組織学会学術大会・第57回マトリックス研究会大会合同学術集会  2010 

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  • CCN2/CTGFはFGF2と結合することで軟骨細胞に対するFGF2作用を修飾する

    第28回日本骨代謝学会学術集会  2010 

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  • CCNファミリータンパク質：新規シグナルコンダクター

    先端歯学スクール2010（教育講演）  2010 

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  • Sox9は血管侵入、骨髄形成および内軟骨性骨形成の最終段階を抑制する—Col10a1-BACトランスジェニックマウスを用いた解析—

    第23回日本軟骨代謝学会  2010 

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  • 軟骨特異的CCN2/CTGF過剰発現による膝間接軟骨の加齢に伴う変性抑制効果

    第23回 日本軟骨代謝学会  2010 

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  • 前十字靭帯細胞におけるCTGF/CCN2の発現

    第23回日本軟骨代謝学会  2010 

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  • 線維芽細胞増殖因子(FGF)2刺激による軟骨細胞増殖促進作用に与える結合組織成長因子(CCN2/CTGF)の影響

    第23回日本軟骨代謝学会  2010 

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  • CCN2/CTGFとCCN3/NOVの結合と軟骨細胞におけるその生理的意義

    第1回骨バイオサイエンス研究会  2010 

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  • 成熟、分化に伴う軟骨細胞形成制御におけるマイクロRNAの役割

    第23回日本軟骨代謝学会  2010 

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  • Role of miR-181a in endochondral ossification: Possible involvement of CCN1

    IADR General Session  2010 

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  • Role of the low-density lipoprotein receptor-related protein-1 in regulation of chondrocyte differentiation.

    第2回岡山医療教育国際シンポジウム,  2009 

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  • CCN2/CTGFのExportin-1による核—細胞質間分子輸送

    第32回日本分子生物学会年会  2009 

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  • 低密度リポタンパク受容体関連タンパク-1（LRP1）の軟骨細胞分化における作用機能

    第32回日本分子生物学会年会  2009 

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  • 二次骨化中心形成過程に発生するオートファジー関連タンパクの局在

    第51回歯科基礎医学会  2009 

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  • CCN2/CTGFとFGFレセプターとの分子間相互作用

    第82回日本生化学会大会  2009 

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  • CCN family 2/connective tissue growth factor (CCN2/CTGF) promotes osteoclastogenesis via interaction with dendritic cell-specific transmembrane protein (DC-STAMP).

    31th Annual Meeting of the ASBMR  2009 

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  • 軟骨細胞におけるCCN2遺伝子の転写後調節機構におけるNucleophosmin/B23の機能的意義

    第82回日本生化学会大会  2009 

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  • 軟骨特異的CCN2/CTGF過剰発現マウスは膝関節軟骨の加齢性変化に抵抗性を示す。

    第82回日本生化学会大会  2009 

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  • 低密度リポタンパク受容体関連タンパク-1（LRP1）の軟骨細胞分化における多面的作用機構

    第82回日本生化学会大会  2009 

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  • 破骨細胞分化に与えるCCNファミリー2/結合組織成長因子(CCN2/CTGF)の促進作用

    第82回日本生化学会大会  2009 

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  • CCN2/CTGFとCCN2/CTGF,およびCCN3/NOVとの結合とそれらの相互作用の解析。

    第30回岡山歯学会総会、学術集会  2009 

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  • Sox9は軟骨において血管侵入を抑制する事によって内軟骨性骨形成の最終段階である骨髄形成を抑制する-Col10a1-BACトランスジェニックマウスを用いた解析-。

    第82回日本生化学会大会  2009 

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  • 軟骨特異的CCN2/CTGF過剰発現マウスは膝関節軟骨の加齢に伴う変形性膝関節症様軟骨変化が抑制され、より正常に近い形質を維持する。

    第32回日本分子生物学会年会  2009 

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  • CCN2/CTGFとFGFレセプターとの結合およびその意義の解析

    第3回日本CCNファミリー研究会  2009 

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  • マイクロRNAによる成長板軟骨細胞特異的ば遺伝子制御

    第3回日本CCNファミリー研究会  2009 

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  • CCN2/CTGFはExportin-1と結合し、細胞核内外を行き来する。

    第3回日本CCNファミリー研究会  2009 

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  • 軟骨特異的CCN2/CTGF過剰発現マウスの膝関節軟骨は加齢後もより正常に近い形質を維持する。

    第3回日本CCNファミリー研究会  2009 

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  • 低密度リポタンパク受容体関連タンパク-1（LRP1）の軟骨細胞分化における多面的作用機構

    第3回日本CCNファミリー研究会  2009 

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  • 軟骨特異的CCN2/CTGF過剰発現は膝関節軟骨を加齢に伴う変性から保護する。

    第51回歯科基礎医学会  2009 

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  • CCNファミリー遺伝子の転写後制御とその生物学的意義

    第3回日本CCNファミリー研究会  2009 

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  • 長管骨組織発生·成長におけるEphA4の遺伝子発現と機能の解析

    第51回歯科基礎医学会  2009 

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  • Nucleophosmin/B23によるChichen CCN2遺伝子の軟骨細胞特異的転写後調節

    第51回歯科基礎医学会  2009 

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  • Chondrocyte-haemopoietic cell interaction that inducea CCN2 and its physiological significance.

    第2回岡山医療教育国際シンポジウム,  2009 

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  • Analysis of transgenic mice overexpressing Ccn2/ctgf in chondrocytes.

    第2回岡山医療教育国際シンポジウム,  2009 

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  • CCN family 2/connective tissue growth factor modulates BMP signaling as a signal conductor, which action regulates the proliferation and differentiation of chondrocytes.

    第2回岡山医療教育国際シンポジウム,  2009 

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  • 骨軟骨再生因子であるCCN2/CTGFとFGFレセプターとの関連

    第19回中国、四国骨代謝研究会  2009 

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  • The regulation of Ccn2/Ctgf gene via micro RNA18a, which suppresses chondrocytes differentiation.

    第2回岡山医療教育国際シンポジウム,  2009 

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  • 低密度リポタンパク受容体関連タンパク-1（LRP1）の軟骨細胞分化における機能とその作用機構

    第27回日本骨代謝学会学術集会  2009 

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  • CCN2/CTGFとFGF受容体との相互作用およびその生物学的意義

    第27回日本骨代謝学会学術集会  2009 

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  • 成長板軟骨細胞後期分化に関与するマイクロRNAの探索

    第27回日本骨代謝学会学術集会  2009 

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  • CCNファミリー2/結合組織成長因子(CCN2/CTGF)はDC-STAMPの遺伝子発現レベルの上昇を介して破骨細胞形成を促進する。

    第27回日本骨代謝学会学術集会  2009 

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  • 軟骨特異的CCN2/CTGF過剰発現は関節軟骨を加齢に伴う変形性関節炎様変化から防御する。

    第27回日本骨代謝学会学術集会  2009 

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  • CCNファミリー2/結合組織成長因子はBMPシグナルを修飾し，軟骨細胞増殖・分化を制御する。

    第22回日本軟骨代謝学会  2009 

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  • Expression and mechanisms of connective tissue growth factor (CCN2/CTGF) induction in osteolytic jaw invasion of human oral squamous cell carcinoma.

    ORS 55th Annual Meeting,  2009 

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  • 受容型チロシンキナーゼEphA4の軟骨細胞および骨芽細胞における機能

    第22回日本軟骨代謝学会  2009 

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  • CCN2/CTGFの軟骨特異的過剰発現は加齢に伴う膝関節軟骨の変性に対して抑制的に働く。

    第22回日本軟骨代謝学会  2009 

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  • 軟骨細胞においてMMP3は核移行しCCN2/CTGFの転写活性化因子として働く。

    第22回日本軟骨代謝学会  2009 

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  • 軟骨・血球系細胞間相互作用によるCCN2の誘導とその生理的意義

    第22回日本軟骨代謝学会  2009 

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  • Micro RNA 18A regulates chondrocytic phenotype: Involvement of CCN2/CTGF as a major target gene.

    IBMS & ANZBMS 2009  2009 

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  • CCN2/CTGF has anti-aging effects to protect articular cartilage from age-related degenerative changes.

    IBMS & ANZBMS 2009  2009 

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  • Distribution, gene expression, and functional role of EphA4 during ossification.

    第2回岡山医療教育国際シンポジウム,  2009 

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  • Interaction of CCN2/CTGFwith BMP-2 regulate the differentiation of human chondrocytic andosteoblastic cell line.

    The 1st International Symposium of Medical and Dental Education in Okayama  2008 

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  • マウス膜性骨化における全CCNファミリーメンバーの役割の包括的解析

    第2回日本CCNファミリー研究会  2008 

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  • CCN2/CTGFの加齢に伴う膝関節軟骨変性抑制効果

    第2回日本CCNファミリー研究会  2008 

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  • Ccn2/ctgf遺伝子のSox9による転写活性化機構

    第2回日本CCNファミリー研究会  2008 

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  • 血小板に含まれるCCN2の由来：造血・間葉系相互作用によるCCN2の蓄積

    第2回日本CCNファミリー研究会  2008 

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  • 軟骨細胞成熟における低密度リポ蛋白受容体関連タンパク-1(LRP1)の関与

    第21回日本軟骨代謝学会  2008 

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  • CCN2/CTGFの軟骨特異的過剰発現マウスモデルの作製と解析

    第21回日本軟骨代謝学会  2008 

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  • CCN2/CTGF軟骨特異的過剰発現マウスの作製とその硬組織の解析

    第49回日本生化学会中国、四国支部例会  2008 

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  • ニコチンがヒト歯周組織由来培養細胞におけるCCN2/CTGF産生に与える影響

    第51回春季日本歯周病学会学術集会  2008 

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  • ノックアウトマウスを用いた顎顔面形成における軟骨由来成長因子CCN2/CTGFの機能解析

    第21回日本軟骨代謝学会  2008 

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  • CCN2/CTGFとBMP-2との分子間相互作用はヒト軟骨細胞様細胞株 HCS-2/8の細胞分化を制御する

    第21回日本軟骨代謝学会  2008 

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  • CCN2/CTGFとBMP-2との結合による軟骨細胞増殖・分化促進作用の制御

    第2回日本CCNファミリー研究会  2008 

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  • マイクロRNA18aによるCcn2/Ctgf遺伝子発現制御機構と、その軟骨細胞分化への関与

    第2回日本CCNファミリー研究会  2008 

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  • 長管骨組織発生、成長におけるEphA4および関連分子の発現と分布の解析

    第18回中国、四国骨代謝研究会  2008 

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  • LRP1による軟骨細胞分化の制御：Wntシグナル経路との関連

    第18回中国、四国骨代謝研究会  2008 

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  • Expression and biological significance of CCN2-associated microRNAs in chondrocytic HCS-2/8 cells.

    The 1st International Symposium of Medical and Dental Education in Okayama  2008 

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  • Distribution and gene expression of EphA4 during long bone development.

    The 1st International Symposium of Medical and Dental Education in Okayama  2008 

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  • Generation and analysis of transgenic mice overexpressing ccn2/ctgf in chondrocytes.

    The 1st International Symposium of Medical and Dental Education in Okayama  2008 

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  • CCN2/CTGF軟骨特異的過剰発現が内軟骨性骨形成に及ばす影響

    第2回日本CCNファミリー研究会  2008 

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  • 結合組織増殖因子(CCN2/CTGF)と歯周組織との関係

    第21回日本歯科医学会総会  2008 

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  • 二次骨化中心形成過程の軟骨分化段階に発生するオートファジー関連タンパクの局在

    第26回日本骨代謝学会学術集会  2008 

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  • 軟骨特異的CCN2/CTGFの過剰発現は骨延長を誘導する

    BMB2008 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会  2008 

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  • Design, synthesis and characterization of CCN2/CTGF anchor peptides.

    BMB2008 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会  2008 

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  • Nicotine Induction of CCN2: from Smoking to Periodontal Fibrosis.

    第56回国際歯科研究学会日本部会学術大会  2008 

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  • CCN2/CTGFと結合するタンパク質の同定

    第29回岡山歯学会  2008 

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  • 受容体型チロシンキナーゼEphA4の軟骨細胞および骨芽細胞における機能

    BMB2008 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会  2008 

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  • 低密度リポタンパク受容体関連タンパク-1(LRP1)の軟骨細胞分化における機能と作用機構

    BMB2008 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会  2008 

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  • CCN2/CTGFとBMP-2の相互作用が軟骨細胞の増殖と分化を制御する

    BMB2008 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会  2008 

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  • マイクロRNA18aによるCcn2/Ctgf遺伝子の制御機構の解明とその軟骨分化における意義

    BMB2008 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会  2008 

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  • ニコチンがヒト歯周組織由来細胞に与える線維化への影響について

    日本歯周病学会 秋季学術大会  2008 

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  • 軟骨細胞分化における低密度リポタンパク受容体関連タンパク-1 (LRP1) の関与

    第26回日本骨代謝学会学術集会  2008 

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  • 軟骨細胞および骨芽細胞におけるEphA4の発現とその意義

    第26回日本骨代謝学会学術集会  2008 

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  • CCN2/CTGFの関節軟骨アンチエイジング作用：軟骨組織特異的CCN2/CTGF過剰発現マウスを用いた解析

    第26回日本骨代謝学会学術集会  2008 

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  • 乳癌および軟骨肉腫細胞におけるMicro RNA 18aのCCN2遺伝子発現抑制様態の比較解析

    第67回日本癌学会総会  2008 

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  • マイクロRNA18aによるCcn2/Ctgf遺伝子を介した軟骨細胞分化の制御機構の解明

    第26回日本骨代謝学会学術集会  2008 

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  • CCN2欠損マウスを用いた、CCN2とCCN3によるPTHrP-Ihhループを介した軟骨細胞分化制御機構の解析

    第26回日本骨代謝学会学術集会  2008 

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  • CCN2/CTGFによるBMP-2の軟骨細胞増殖、分化促進作用の制御

    第26回日本骨代謝学会学術集会  2008 

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  • 骨軟骨再生因子CCN2/CTGFのモジュール別結合ペプチド配列の探索とその応用

    第26回日本骨代謝学会学術集会  2008 

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  • CCN2/CTGFの軟骨特異的過剰発現が内軟骨性骨形成に及ばす影響

    第26回日本骨代謝学会学術集会  2008 

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  • Phage Display法によるCCN2/CTGFのモジュール別結合ペプチド配列の探索とその有用性

    第50回歯科基礎医学会学術大会  2008 

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  • CCN2ノックアウトマウスを用いた骨芽細胞分化におけるCCNタンパク質の機能解析

    第67回日本矯正学会大会  2008 

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  • Overexpression of CCN2/CTGF in cartilage shows prolonged bone length resulting from stimulation of chondrogenesis, chondrocyte growth, apoptosis, and bone mineralization during endochondral ossification

    30th Annual Meetingof the American Society for Bone and Mineral Research  2008 

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  • 軟骨細胞分化におけるCCN2/CTGF受容体、低密度リポタンパク受容体関連タンパク-1(LRP1)の多面的関与

    第2回日本CCNファミリー研究会  2008 

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  • Nucleophhosmin/B23: A multifunctional regulator that determines the fate of ccn2 mRNA.

    The 5th International Workishop on the CCN Family of Genes  2008 

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  • CCN2/CTGF is transactivated through its enhancer element by Sox9 in fibroblasts: possible roles in fibrosis

    The 5th International Workishop on the CCN Family of Genes  2008 

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  • Roles of CCN2 in skeletal growth and regeneration - Requirment for both endochondral and intramembranous bone formation-

    The 5th International Workishop on the CCN Family of Genes  2008 

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  • The roles of CCN family 2/connective tissue growth factor (CCN2/CTGF) in skeletal development: Generation and analysis of transgenic mice overexpressing CCN2/CTGF in cartilage-

    13 World Congress on Advances in Oncology and 11th International Syｍposium on Molecular Medicine  2008 

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  • Novel transcriptional regulation of CCN2/CTGF by nuclear translocated MMP3.

    The 5th International Workishop on the CCN Family of Genes  2008 

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  • Regulation of chondrocytic phenotype by micro RNA 18a: Involvement of Ccn/Ctgf as a major target gene.

    The 5th International Workishop on the CCN Family of Genes  2008 

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  • 破骨細胞形成におけるCCN2/CTGFの役割

    第2回日本CCNファミリー研究会  2008 

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  • 軟骨細胞および骨芽細胞における受容体型チロシンキナーゼEphA4の機能：CCN2/CTGFとの関連

    第2回日本CCNファミリー研究会  2008 

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  • CCN2/CTGFのモジュール別結合ペプチド配列の探索とその応用

    第2回日本CCNファミリー研究会  2008 

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  • Induction of CCN2/CTGF by fluid flow stress via Rho signaling in osteoblastic cells.

    第2回日本CCNファミリー研究会  2008 

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  • ヒト歯周組織由来培養細胞における喫煙と線維化との関係へのニコチン誘導性CCN2/CTGFの関与

    第2回日本CCNファミリー研究会  2008 

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  • 癌顎骨切除標本におけるCCN2の臨床病理学的検討。

    第1回日本CCNファミリー研究会  2007 

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  • 軟骨細胞においてマトリックス金増苦プロテアーゼ-3（MMP3）は核移行し結合組織成長因子（CCN2/CTGF）の転写因子として働く

    第30回日本分子生物学会年会・第80回日本生化学大会 合同大会 ワークショップ  2007 

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  • Expression and biological significance of CCN2-associated noncoding RNAs in chondrocytic HCS-2/8 cells.

    第30回日本分子生物学会年会・第80回日本生化学会大会 合同大会  2007 

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  • 結合組織成長因子（CCN2/CTGF）とアグリカンとの結合についての解析。

    第30回日本分子生物学会年会・第80回日本生化学会大会 合同大会，  2007 

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  • 軟骨特異的にCCN2/CTGFを過剰発現したトランスジェニックマウスの作製と解析。

    第30回日本分子生物学会年会・第80回日本生化学会大会  2007 

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  • Functional analysis of the low density lipoprotein receptor-related protein (LRP1) in chondrocytes.

    第30回日本分子生物学会年会・第80回日本生化学会大会 合同大会  2007 

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  • 軟骨細胞におけるCCNファミリー2/結合組織成長因子(CCN2/CTGF)のオートクリン発現メカニズムの解明。

    第30回日本分子生物学会年会・第80回日本生化学会大会 合同大会  2007 

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  • Effect of TGF-β1 on CCN2/CTGF in human gingival fibroblasts and periodontal ligament cells.

    第127回日本歯科保存学会 秋季学術大会  2007 

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  • 培養軟骨細胞株及び半月板細胞におけるCCNファミリー2/結合組織成長因子(CCN2/CTGF)発現に与えるメカニカルストレスの影響。

    第1回日本CCNファミリー研究会  2007 

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  • Effect of TGF-β1 on CCN2/CTGF in human gingival fibroblasts and periodontal ligament cells.

    第1回日本CCNファミリー研究会  2007 

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  • ラット咬筋の持続反復電気刺激はCCN2の遺伝子発現を亢進する。

    第1回日本CCNファミリー研究会  2007 

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  • 圧負荷肥大心ではCCN2はBrain Natriuretic Peptideと拮抗して心臓線維化をもたらす。

    第1回日本CCNファミリー研究会  2007 

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  • CCNファミリー2/結合組織成長因子(CCN2/CTGF)と骨形成因子(BMP)-2の相互作用が軟骨細胞及び骨芽細胞分化に与える影響。

    第1回日本CCNファミリー研究会  2007 

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  • 軟骨特異的にCCN2/CTGFを過剰発現したトランスジェニックマウスの作製と軟骨内骨化におけるCCN2/CTGFの役割解析

    第１回 日本CCNファミリー研究会  2007 

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  • Functional analysis of a CCN2/CTGF receptor, the low density lipoprotein receptor-related protein (LRP1), in chondrocytes

    第1回日本CCNファミリー研究会  2007 

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  • CCN2ノックアウトマウスを用いた骨芽細胞分化におけるCCNファミリータンパク質の機能解析。

    第1回日本CCNファミリー研究会  2007 

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  • 結合組織成長因子(CCN2/CTGF)結合タンパク質の同定および軟骨細胞におけるその結合の生理的意義

    第20回日本軟骨代謝学会  2007 

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  • 軟骨細胞におけるCCN2/CTGFの四つのモジュールの異なった役割.

    第1回日本CCNファミリー研究会  2007 

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  • 癌の浸潤・腫瘍性血管新生における全CCNファミリーメンバーの果たす役割の包括的解析。

    第1回日本CCNファミリー研究会  2007 

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  • CCNファミリー：新規シグナルコンダクター

    第１回日本ＣＣＮファミリー研究会オーバービュー講演  2007 

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  • 軟骨特異的CCN2/CTGF過剰発現トランスジェニックマウスの作製とCCN2/CTGFの内軟骨性骨化に及ぼす影響について

    第49回歯科基礎医学会学術集会  2007 

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  • 長管骨組織におけるEphA4の遺伝子発現と分布の解析。

    第49回歯科基礎医学会学術集会  2007 

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  • CCNファミリー2/結合組織成長因子(CCN2/CTGF)が骨芽細胞において骨形成因子(BMP)-2刺激による骨芽細胞分化を修飾する。

    第28回岡山歯学会学術大会  2007 

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  • Effect of nicotine on CCN2/CTGF in human periodontal tissue.

    11th Biennial Congress of the International Academy of Periodontology.  2007 

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  • 軟骨成長・分化因子CCN2/CTGFとMatrilin3との相互作用。

    第49回歯科基礎医学会学術集会  2007 

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  • ラット大腿骨骨折治癒過程におけるCTGF発現と破軟骨細胞の配置。

    第49回歯科基礎医学会学術集会  2007 

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  • CCN2ノックアウトマウスを用いたCCN2およびCCN3の軟骨分化における機能解析。

    第49回歯科基礎医学会学術集会  2007 

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  • CCN2遺伝子関連ノンコーディングRNAの軟骨細胞様HCS-2/8 細胞における発現。

    第28回岡山歯学会学術大会  2007 

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  • Physilogical and pathological roles of CCN2.

    Lecture at Department of Dermatology Michigan University Medical School  2007 

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  • CTGF/CCN2 in bone metastasis and tumor angiogenesis.

    Gordon Research Conference on SIBLING (invitation)  2007 

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  • 長管骨組織におけるEphA4の分布と遺伝子発現の解析

    第28回岡山歯学会学術大会  2007 

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  • 結合組織成長因子(CCN2/CTGF)とアグリカンとの結合の生理的意義の解析

    第25回日本骨代謝学会学術集会  2007 

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  • 成長板軟骨細胞におけるCCN4/WISP1 mRNAおよびそのスプライシングバリアントの発現とその機能

    第25回日本骨代謝学会学術集会  2007 

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  • CCN2/CTGF過剰発現トランスジェニックマウスの作製によるCCN2/CTGFの内軟骨性骨化における役割解明

    第25回日本骨代謝学会学術集会  2007 

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  • CCN2ノックアウトマウスを用いた骨芽細胞分化におけるCCNファミリータンパク質の機能解析

    第25回日本骨代謝学会学術集会  2007 

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  • Tip60によるSox9, Sox5のクロマチンを介した軟骨分化の制御 (Transcriptional regulation of chondrogenesis by coactivator Tip60 via chromatin association with Sox9 and Sox5)

    第25回日本骨代謝学会学術集会  2007 

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  • 軟骨細胞におけるCCNファミリー2/結合組織成長因子(CCN2/CTGF)によるVEGF遺伝子発現制御機構の解明

    第25回日本骨代謝学会学術集会  2007 

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  • ２型コラーゲンプロモーターで誘導したCCN2/CTGF過剰発現トランスジェニックマウスの作製による軟骨分化におけるCCN2/CTGFの役割解析

    第17回中国・四国骨代謝研究会  2007 

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  • 軟骨細胞における低密度リポタンパク受容体関連タンパク1(LRP1)の機能の解析

    第17回中国・四国骨代謝研究会  2007 

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  • Role of mechanical-stress inducible protein HCS24/CTGF/CCN2 in cartilage growth and regeneration.

    5th International Symposium on mechanobiology of cartilage and chondrocyte. (invitation)  2007 

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  • Role of CCN2 in skeletal growth and regeneration.

    Meeting Scientifici Dipartimento di Oncologia Muscoloscheletrica, Instituti Orthopedici Rizzoli  2007 

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  • ウサギ半月板細胞におけるCCNファミリー2/結合組織成長因子(CCN2/CTGF)発現に与えるメカニカルストレスの影響

    第25回日本骨代謝学会学術集会  2007 

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  • 軟骨細胞において結合組織成長因子/CCNファミリー2 (CTGF/CCN2)はHIF-1aの発現を介してVEGF発現を制御する

    第20回日本軟骨代謝学会  2007 

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  • 軟骨細胞にみられる低密度リポタンパク受容体関連タンパク1(LRP1)の局在と機能の解析発現

    第20回日本軟骨代謝学会  2007 

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  • 成長板軟骨細胞と軟骨肉腫細胞株におけるCCN4/WISP1 mRNAおよびそのスプライシングバリアントの発現とその機能

    第20回日本軟骨代謝学会  2007 

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  • CCN2ノックアウトマウスを用いたCCN3の軟骨分化における機能解析

    第20回日本軟骨代謝学会  2007 

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  • 軟骨細胞における低密度リポタンパク受容体関連タンパク1(LRP1)の発現とその機能

    第19回日本軟骨代謝学会  2006 

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  • Alveolar bone regeneration using human bone marrow stromal cells and CCN2 －To attain reliable and sorhisticated dental implant therapy-

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • Identification of CCN2/CTGF binding proteins from human chondrocytes.

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • CCN2はフィブロネクチン及びマトリリン3と相互作用し、軟骨細胞の接着及び細胞外マトリックスの重合を制御している

    第27回岡山歯学会  2006 

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  • Concluding Remarks

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • Roles of CCN proteins in skeletal growth and regeneration,

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • 骨髄由来間質細胞の接着・増殖・遊走に及ぼす結合組織成長因子CCN2/CTGFの効果 －多孔質ハイドロキシアパタイトを用いた細胞移植治療に向けて－

    2006 

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  • 結合組織成長因子CCN2/CTGFによる骨髄由来間質細胞の細胞接着，遊走の亢進とシグナル伝達経路の活性化

    第24回日本骨代謝学会学術集会  2006 

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  • WNT-induced secreted protein 1 (WISP1/CCN4) mRNA splicing variants in normal and transformed chondrocytes.

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • Expression and possible function of a CCN2 receptor, low density lipoprotein receptor-related protein 1 (LRP1), in chondrocytes.

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • Introductory Talk

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • Purification and functional characterization of a protein that regulate ccn2 gene expression during chicken chondrocyte differentiation.

    The 28th Annual Meeting of the American Society for Bone and Mineral Research  2006 

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  • Promotion of adhesion and migration of human bone marrow stromal cells by CCN2 －Mechanism and Utility in bone regeneration-

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • Effect of CCN2 deletion on the expression of the other CCN family members during chondrocytic terminal differentiation.

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • CT domain of CCN2/CTGF directly interacts with fibronectin and enhances cell adhesion of chondrocytes through integrin alpha5beta1.

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • Possibility of articular cartilage reconstruction with CCN2/CTGF.

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • Searching for CCN2/CTGF binding proteins to modulate physiological roles of the CCN2/CTGF.

    20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress  2006 

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  • Roles of CCN2/CTGF in the control of skeletal growth, remodeling and regeneration.

    84th Annual Meeting of International Association for Dental Research  2006 

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  • Expression and possible function of the low density lipoprotein receptor-related protein 1 (LRP1) in chondrocytes.

    20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress  2006 

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  • Two Wnt-induced secreted protein 1 (WISP1/CCN4) mRNA splicing variants in normal and transformed chondrocytes.

    20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress  2006 

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  • Induction mechanism of ccn4/wisp1 gene expression in human chondrocytic and osteoblastic cells.

    20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress.  2006 

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  • CCN2ノックアウトマウスを用いた内軟骨性骨化過程におけるCCNファミリーメンバーの役割解析.

    第24回日本骨代謝学会学術集会  2006 

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  • CCNファミリータンパク質の内軟骨性骨化制御機構と骨・軟骨再生作用

    第24回日本骨代謝学会学術集会  2006 

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  • CCN2/CTGF as a multifunctional factor for hBMSC toward bone formation.

    IADR 81st General Session and Exhibition  2006 

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  • 結合組織成長因子(CTGF/CCN2)欠損マウス由来軟骨細胞における細胞接着活性の低下とIntegrin signalingの障害

    第24回日本骨代謝学会学術集会  2006 

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  • 軟骨成長板で産生が確認されたCCN4/WISP1の遺伝子発現調節機構

    第19回日本軟骨代謝学会  2006 

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  • CCN2/CTGF刺激は軟骨細胞でリウマチ関連抗原HSP47/RA-A47の発現量を減少させる－リウマチ病態および軟骨組織の修復との関連性についての考察－

    第19回日本軟骨代謝学会  2006 

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  • 成長板軟骨細胞と軟骨肉腫由来の軟骨細胞株におけるCCN4/WISP1 mRNAおよびそのスプライシングバリアントの発現

    第19回日本軟骨代謝学会  2006 

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  • LC-MS/MSシステムを利用した核内MMP-3共役因子の網羅的解析 疾患プロテオミクス

    学内COE 公開シンポジウム  2006 

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  • Transcriptional regulation of chondrogenesis by coactivator Tip60 via chromatin association with Sox9 and Sox5.

    20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress  2006 

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  • Expression of CTGF mRNA and induction of apoptosis in osteocytes by mechanical stimulation in mice.

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • CCN2 (Connective tissue growth factor) supports the binding of fibronectin to alpha5beta1 integrin and maintains integrin signaling.

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • The role of CCN2 in the development of cardiac fibrosis and its clinical utility for the diagnosis of heart failure

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • The 3’-untranslated region-mediated regulation of the CCN family genes.

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • Role and mechanism of connective tissue growth factor (CCN2/CTGF) induction in osteolytic metastasis of breast cancer.

    Fourth International Workishop on the CCN Family of Genes  2006 

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  • 軟骨細胞における低密度リポタンパク質受容体関連タンパク１(LRP1)の発現。細胞表面への露出を引き起こす：関節リウマチにおける自己抗原としての認識機構

    第18回日本軟骨代謝学会  2005 

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  • 転写活性化因子Tip60のSox9,Sox5複合体への会合を介した軟骨分化の制御．

    第２８回日本分子生物学会年会  2005 

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  • 軟骨組織及び軟骨細胞における低密度リポタンパク受容体関連タンパク１(LRP-1)の遺伝子発現とタンパク質局在

    第２８回日本分子生物学会年会ワークショップ  2005 

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  • MMP-3/Stromelysin-1 acts as a transcription modulator targeting ccn2 in chondrocytes.

    第２８回日本分子生物学会年会ワークショップ  2005 

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  • 転写因子Sox9, P53の活性制御機構ﾑSUMO化との関連は？

    第２８回日本分子生物学会年会  2005 

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  • CTGF刺激によるヒト歯髄細胞におけるオステオネクチンの発現の解析

    第1回日本再生歯科医学会  2005 

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  • Determination of a core segment that is involved in the repressive regulation by human ccn1 3'-UTR.

    第78回日本生化学会大会  2005 

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  • Hypoxic regulation of hypertrophic chondrocyte specific gene product 24/connective tissue growth factor/CCN2 mRNA by 3'-untranslated region interacting with a cellular protein.

    第78回日本生化学会大会  2005 

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  • Differential expression of CCN4/Wisp1 mRNA splicing variants in normal and malignant-transformed chondrocytes.

    第53回国際歯科研究学会学術大会  2005 

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  • Interplay of Connective Tissue Growth Factor and Brain Natriuretic Peptide Secreted by Cardiac Myocytes Regulates Collagen Production in Cardiac Fibroblasts.

    American Heart Association Scientific Meeting  2005 

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  • 軟骨組織の成長分化、再生とCCN遺伝子ファミリー

    第53回国際歯科研究学会学術大会シンポジウム  2005 

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  • ヒト歯髄由来間葉系幹細胞の細胞接着ならびに増殖に対する各種成長因子の影響

    第1回日本再生歯科医学会  2005 

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  • CCN2/CTGF interacts with fibronectin 1 and enhances cell adhesion（CCN2/CTGFはfibronectin1と相互作用して細胞接着能を高める）．

    The 53rd Annual Meeting of Japanese Association for Dental Research（国際歯科研究学会日本部会(JADR)総会・学術大会）  2005 

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  • CCN2 supports the binding of fibronectin to a5b1 integrin and maintains integrin signaling.

    53rd Annual Meeting of Japanese Association for Dental Research  2005 

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  • Production and role of the M-CSF in various chondrocytes.

    第53回国際歯科研究学会学術大会  2005 

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  • 軟骨細胞におけるCCN family メンバーのdexamethasoneによる遺伝子発現調節

    第47回歯科基礎医学会学術大会  2005 

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  • 関節および成長軟骨細胞におけるM-CSFの産生と役割

    第47回歯科基礎医学会学術大会  2005 

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  • Determination of a core segment that is involved in the repressive regulation by human ccn1 3'-UTR.

    第78回日本生化学会大会ワークショップ  2005 

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  • Connective tissue growth factor (CTGF/CCN2) reinforces the molecular phenotype of auricular chondrocytes in vitro.

    The 27th Annual Meeting of the American Society for Bone and Mineral Research  2005 

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  • 新規血管新生阻害剤DN-9693の作用機序：VEGFによる血管新生因子CTGF/CCN2の発現レベル上昇に対する阻害効果

    第64回日本癌学会学術総会ワークショップ  2005 

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  • デキサメタゾン刺激はCCN2/CTGFの誘導を介して軟骨細胞のリウマチ関連抗原HSP47/RA-A47の発現量を減少させる－リウマチ病態および軟骨組織の修復との関連性について－

    第47回歯科基礎医学会学術大会  2005 

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  • Modulation of CCN family member gene expression in chondrocytes by dexamethasone

    第78回日本生化学会大会  2005 

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  • Wnt-induced secreted protein 1 (Wisp1/CCN4) mRNA splicing variants in a human chondrosarcoma-derived chondrocytic cell line (HCS-2/8).

    第78回日本生化学会大会  2005 

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  • Modulation of CCN family member gene expression in chondrocytes by dexamethasone

    第78回日本生化学会大会ワークショップ  2005 

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  • Hypoxic regulation of hypertrophic chondrocyte specific gene product 24/connective tissue growth factor/CCN2 mRNA by 3'-untranslated region interacting with a cellular protein.

    第78回日本生化学会大会ワークショップ  2005 

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  • 軟骨細胞における低密度リポタンパク受容体関連タンパク１(LRP1)の遺伝子発現とタンパク質局在

    第23回日本骨代謝学会学術集会  2005 

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  • 血小板に含まれる結合組織成長因子 (CTGF/CCN2) とその組織再生における役割

    第37回日本結合組織学会  2005 

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  • 低酸素組織、軟骨における肥大軟骨特異的蛋白24/結合組織成長因子/CCNファミリー2mRNAの安定化機構〜核および細胞質タンパク結合を介した3'-非翻訳領域(UTR)の関与〜

    第23回日本骨代謝学会学術集会  2005 

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  • CCN2/CTGFはコラーゲン特異的分子シャペロンHSP47/リウマチ関連抗原RA-A47の発現量を減少させるーリウマチ病態および軟骨組織の修復との関連ー

    第23回日本骨代謝学会学術集会  2005 

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  • Post-transcriptional regulation of CCN2/CTGF gene expression during differentiation of chicken chondrocytes: Involvement of a putative trans-factor which interacts with a cis-element in the 3ﾕ-UTR of mRNA

    30th FEBS Congress - 9th IUBMB Conference  2005 

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  • 内軟骨性骨化・軟骨再生とCCNファミリータンパク質

    第23回日本骨代謝学会ミニシンポジウム  2005 

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  • 二次骨化中心形成過程に発現する結合組織成長因子CTGF/CCN2のパールカン陽性細胞への特異的集積

    第23回日本骨代謝学会学術集会  2005 

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  • 骨・軟骨細胞におけるCCN familyの遺伝子発現とその制御機構の比較解析

    第23回日本骨代謝学会学術集会  2005 

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  • 軟骨由来多機能成長因子CCN2/CTGF/Hcs24は耳介軟骨細胞の形質発現を増強する

    第23回日本骨代謝学会学術集会  2005 

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  • 各種軟骨細胞におけるM-CSFの産生とその生理的役割

    第23回日本骨代謝学会学術集会  2005 

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  • PIAS proteins interact directly with Sox9 and modifiy Sox9 activity through SUMOylation.

    Gordon Conference: Biology and Pathology of Cartilage  2005 

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  • 変形性関節症においても、２型腫瘍壊死因子可溶性受容体は関節破壊や炎症を調節する

    第18回日本軟骨代謝学会  2005 

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  • コラーゲン特異的分子シャペロンHSP47/RA-A47の発現量低下が軟骨細胞の破壊とHSP47/RA-A47の細胞表面への露出を引き起こす：関節リウマチにおける自己抗原としての認識機構。

    第18回日本軟骨代謝学会  2005 

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  • 関節リウマチ関連抗原HSP47/RA-A47の細胞内発現抑制は、それ自身の細胞表面への局在変化と軟骨細胞のアポトーシスを誘導するー関節リウマチ発症との関連―

    第24回岡山免疫懇話会  2005 

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  • 胎児発生に必須な遺伝子cyr61に存在する発現調節機能の解析。

    第25回岡山歯学会総会  2005 

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  • 変形性関節症モデルにおけるM-CSFの産生と修復における意義

    第18回日本軟骨代謝学会  2005 

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  • 耳介軟骨細胞に対する結合組織成長因子(CTGF/CCN2)の効果

    第18回日本軟骨代謝学会  2005 

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  • 二次骨化中心形成過程におけるCTGF/CCN2およびMMP-9の発現と局在

    第18回日本軟骨代謝学会  2005 

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  • 軟骨細胞における関節リウマチ関連抗原RA-A47の発現抑制による軟骨破壊因子の誘導とRA-A47自身の細胞表面への露出

    第48回日本リウマチ学会総会  2004 

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  • 関節軟骨細胞の修復と維持にM-CSFとCTGFの協調的誘導が関与する

    第17回日本軟骨代謝学会  2004 

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  • 軟骨細胞の分化過程におけるニワトリ結合組織成長因子（CTGF/Hcs24）遺伝子の転写後発現調節機構の解析

    第17回日本軟骨代謝学会  2004 

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  • 軟骨組織形成に重要なヒトcry61遺伝子の発現調節の解析

    第17回日本軟骨代謝学会  2004 

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  • Taurine transporter in human chondrosarcoma HCS-2/8 cells.

    Annual Meeting of American Orthopaedic Research Society.  2004 

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  • 結合組織成長因子CTGF/CCN2によるラット関節軟骨の再生

    第3回日本再生医療学会  2004 

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  • 関節炎軟骨からのカルパイン分泌に対するNSAIDsの阻害作用

    第17回日本軟骨代謝学会  2004 

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  • 血小板に見いだされた結合組織成長因子/肥大軟骨細胞特異的遺伝子産物24（CTGF/Hcs24/CCN2)

    第17回日本軟骨代謝学会  2004 

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  • 15dPGJ2によるヒト軟骨肉腫細胞のアポトーシス誘導機序におけるｐ２１の関与

    第17回日本軟骨代謝学会  2004 

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  • 骨，軟骨修復を促進する血小板中の結合組織成長因子(CTGF/CCN2)

    第22回日本骨代謝学会学術集会  2004 

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  • ヒト血小板中connective tissue growth factor (CTGF/CCN2) の定量解析

    第77回日本生化学会大会  2004 

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  • 軟骨組織形成に重要なヒトcyr61遺伝子の発現調節の解析

    第77回日本生化学会大会ワークショップ  2004 

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  • 結合組織成長因子 (CTGF/CCN2) を構成するモジュールの機能解析

    第77回日本生化学会大会ワークショップ  2004 

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  • Regeneration of defects in articular cartilage in rat knee joints by connective tissue growth factor/ hypertrophic chondrocyte-specific gene product 24/ CCN family protein 2 (CTGF/Hcs24/CCN2).

    The 26th Annual Meeting of the American Society for Bone and Mineral Research  2004 

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  • 軟骨細胞の分化過程におけるCCN2/CTGF遺伝子転写後発現調節機構の解析

    第46回歯科基礎医学会学術大会  2004 

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  • ニワトリ軟骨細胞の分化過程におけるCTGF/Hcs24遺伝子の転写後発現調節機構の解析

    第22回日本骨代謝学会学術集会  2004 

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  • 関節軟骨細胞におけるM-CSFとCTGFの協調的誘導とその効果

    第22回日本骨代謝学会学術集会  2004 

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  • 軟骨細胞におけるM-CSFとCTGFの協調的誘導とその効果

    第46回歯科基礎医学会学術大会  2004 

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  • 低酸素におけるCTGF mRNAの安定化機構〜核内タンパク質結合を介した3'-非翻訳領域(UTR)の関与

    第63回日本癌学会学術総会ワークショップ  2004 

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  • コラーゲン特異的分子シャペロンRA-A47/HSP47：関節リウマチにおける自己抗原としての認識機構

    第22回日本骨代謝学会学術集会  2004 

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  • 二次骨化中心形成過程における結合組織成長因子CTGF/CCN2の発現−血管新生因子としての関与−

    第22回日本骨代謝学会学術集会  2004 

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  • Hypoxic regulation of the stability of connective tissue growth factor by a cytoplasmic protein which binds to the 3'-untranslated region in human chondrosarcoma cells.

    第27回日本分子生物学会年会  2004 

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  • Analysis of the human cyr61/ccn1 gene regulation which is medated by the 3'-UTR

    第27回日本分子生物学会年会  2004 

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  • Connective Tissue Growth Factor(CTGF/CCN2)プロモーター上の３つのシスエレメント＜軟骨細胞優位型エンハンサー(TRENDIC)、スマッド結合配列(SBE)、TGF-beta応答領域(TbRE)＞の機能比較−軟骨細胞様細胞株HCS-2/8と乳癌細胞株MDA231における違い−

    第27回日本分子生物学会年会  2004 

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  • 軟骨特異的転写因子Sox9のSUMO化による活性調節（Regulation of transcription activity of chondrocytes-specific factor Sox9 by SUMOylation）,ワークショップ, SUMO修飾による分子複合体の機能、構造変換

    第27回日本分子生物学会年会  2004 

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  • 軟骨細胞での低密度リポ蛋白レセプター関連蛋白 (LRP1) の発現

    第77回日本生化学会大会  2004 

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  • 結合組織成長因子 (CTGF/CCN2) を構成するモジュールの機能解析

    第77回日本生化学会大会  2004 

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  • 軟骨組織形成に重要なヒトcyr61遺伝子の発現調節の解析

    第77回日本生化学会大会  2004 

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  • Differential regulation of CTGF/CCN2 transcription in MDA231 breast cancer cell line and HCS-2/8 chondrocytic cell line.

    Third International Workshop on the CCN Family of Genes  2004 

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  • The roles of CCN2 in skeletal repair and regeneration.

    Third International Workshop on the CCN Family of Genes  2004 

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  • CCN2 gene regulation in chondrocytic differentiation.

    Third International Workishop on the CCN Family of Genes  2004 

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  • CEF-10/Cyr61遺伝子の翻訳領域の5'末端部分の遺伝子発現cisエレメントとしての役割の解析

    第16回日本軟骨代謝学会  2003 

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  • The CCN family of genes: Novel matricellular proteins.

    第76回日本生化学会大会シンポジウム  2003 

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  • Repressive mechanisms of CTGF/Hcs24 gene expression in a human squamous cell carcinoma-derived cell line.

    第76回日本生化学会大会  2003 

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  • Induction of connective tissue growth factor by hypoxia in human chondrosarcoma cell line, Hcs2/8, througe p38 signaling cascade: Coregulation with matrix metalloproteinases.

    第76回日本生化学会大会  2003 

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  • 非翻訳領域を介したctgf/ccn2とcyr61/ccn1の遺伝子発現制御

    第26回日本分子生物学会年会シンポジウム  2003 

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  • ヒト間葉系幹細胞の全遺伝子発現プロファイルとエピジェネティック解析―その再生医療への応用

    第26回日本分子生物学会シンポジウム（オーガナイザー）  2003 

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  • Molecular regulation of CTGF/Hcs24/CCN2 that regulates chondrocyte growth and differentiation.

    第76回日本生化学会大会シンポジウム  2003 

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  • CCN/Notch signal interaction.

    第76回日本生化学会大会シンポジウム  2003 

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  • 軟骨細胞の分化過程におけるニワトリ結合組織成長因子（CTGF/Hcs24）遺伝子の転写後発現調節機構の解析

    第26回日本分子生物学会年会  2003 

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  • CCN3(NOV)の細胞増殖・分化における役割

    第26回日本分子生物学会年会シンポジウム  2003 

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  • CCN遺伝子ファミリー研究の最前線

    第26回日本分子生物学会年会シンポジウム  2003 

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  • Tyrosine kinase-type receptors erbB4 and m-csfr/c-fms gene expression in chondrocytes.

    IADR 81st General Session and Exhibition  2003 

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  • Transcriptional induction of the gene encoding alpha3 chain of thpe IX collagen (Col9A3) by Sox9 contributes to the susceptibility of knee osteoarthritis.

    25rd Annual Meeting of the ASBMR  2003 

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  • Gene expression profile of human chondrosarcoma cell line HCS 2/8 by high-throughout EST sequencing analysis.

    25rd Annual Meeting of the ASBMR  2003 

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  • Induction of connective tissue growth factor/hypertrophic chondrocyte-specific 24/CCN2 gene by dexamethasone in human chondrocytic cells: Mechanism and biological outcome.

    25rd Annual Meeting of the ASBMR  2003 

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  • CTGF/Hcs24/CCN2, Hypertrophic chondrocyte-specific gene product, interacts with perlecan in regulating the proliferation and defferntination of chondrocytes.

    25rd Annual Meeting of the ASBMR  2003 

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  • Induction of connective tissue growth factor/hypertrophic chondrocyte-specific 24/CCN2 gene by dexamethasone in human chondrocytic cells: Mechanism and biological outcome.

    ASBMR 25rd Annual Meeting  2003 

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  • Cloning of cDNAs encoding TREDNDIC-binding proteins in HCS-2/8 chondrocytic cell line.

    第76回日本生化学会大会  2003 

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  • Regeneration of injured rat articular cartilage by connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24(CTGF/Hcs24/CCN2).

    第76回日本生化学会大会  2003 

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  • The CCN Family of Genes: Novel Matricellular Proteins-Overview-.

    第76回日本生化学会大会  2003 

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  • ヒト軟骨肉腫培養細胞株における結合組織成長因子（CTGF）の低酸素による誘導はp38MAPK経路を介している

    第62回日本癌学会総会  2003 

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  • Regeneration of defects in the articular cartilage in rat knee joints by connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24(ctgf/hcs24).

    1st Joint Meeting of the International Bone and Mineral Society and the Japanese Society of Bone and Mineral Research  2003 

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  • 肥大軟骨由来の成長因子CTGF/Hcs24によるラット間接軟骨損傷の修復

    第21回日本骨代謝学会ワークショップ  2003 

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  • Transcriptional induction of connective tissue growth factor/ hypertrophic chondrocyte-specific 24 gene by dexamethasone in human chondrocytic cells.

    1st Joint Meeting of the International Bone and Mineral Society and the Japanese Society of Bone and Mineral Research  2003 

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  • The effect of the 5' end of the open reading frame of cer-10/cyr61 mRNA as a cis element of gene expression.

    1st Joint Meeting of the International Bone and Mineral Society and the Japanese Society of Bone and Mineral Research  2003 

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  • Coordinated gene induction and repression of two ccn family members, ctgf and cyr61, in chondrocytic cells.

    1st Joint Meeting of the International Bone and Mineral Society and the Japanese Society of Bone and Mineral Research  2003 

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  • モジュール特異的抗体による結合組織成長因子CTGF/Hcs24の構造と機能の解析

    第45回歯科基礎医学会  2003 

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  • 軟骨細胞におけるm-csfr/c-fms の発現と意義

    第45回歯科基礎医学会  2003 

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  • Role of connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 in skeletal growth,

    University of Erlangen-Nuremberg 講演会  2003 

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  • Role of connective tissue growth factor/hypertrophic chondrocyte specific gene product 24 (CTGF/Hcs24) in skeletal growth.

    Kuopio University Seminar  2003 

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  • ErbB2のノックアウトマウスにおける肥大軟骨のアポトーシス

    第45回歯科基礎医学会  2003 

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  • CTGF/Hcs24を軟骨組織で強制発現したtransgenic mouseの解析

    第15回日本軟骨代謝学会  2003 

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  • 結合組織成長因子(CTGF/hcs24)遺伝子3'-非翻訳領域の遺伝子発現作用の脊椎動物種間における構造的・機能的比較

    第15回日本軟骨代謝学会  2003 

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  • 肥大軟骨細胞由来の成長因子CTGF/Hcs24によるラット関節軟骨損傷の修復

    第16回日本軟骨代謝学会  2003 

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  • 軟骨細胞に特異的な新規転写調節スイッチ同定の試み

    第16回日本軟骨代謝学会  2003 

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  • Connective tissue growth factor(CTGF)の軟骨細胞特異的な転写調節機構の探索

    第44回日本生化学会中国・四国支部例会  2003 

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  • The role of mechnical force in the production of inflammatory mediators by articular cartilage.

    International Symposium at the 47th Annual Meeting of Japanese College of Reumatology  2003 

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  • 軟骨細胞の肥大化におけるAPIとCTGF/Hcs24/ecogeninの相互作用

    第15回日本軟骨代謝学会  2003 

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  • 軟骨由来成長因子CTGF/Hcs24/ecogeninの構成モジュール特異的抗体の解析とその応用

    第15回日本軟骨代謝学会  2003 

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  • 軟骨細胞におけるマクロファージコロニー刺激因子受容体遺伝子（m-csfr/c-fms）の発現と意義

    第21回日本骨代謝学会  2003 

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  • Role of CTGF/Hcs24/CCN2/ecogenin in skeletal growth control.

    5th Pan Pacific Connective Tissue Society Symposium  2003 

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  • High hydrostatic pressure induces actibation of ERK signaling pathway in human chondrosarcoma HCS-2/8 cells.

    Annual Meeting of American Orthopaedic Research Society.  2003 

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  • ラット下顎頭軟骨、大腿骨関節軟骨、大腿骨骨端成長板軟骨における結合組織成長因子(CTGF)の発現

    第16回日本軟骨代謝学会  2003 

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  • DNAマクロアレイによるヒト間葉系幹細胞の遺伝子発現プロファイル解析

    第16回日本軟骨代謝学会  2003 

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  • Driving the Driver: Molecular regulation of CTGF/Hcs24 that regulates chondrocyte growth and differentiation.

    第16回日本軟骨代謝学会  2003 

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  • ラット軟骨細胞に対するメカニカルストレス後の遺伝子発現とIL-4の影響

    第16回日本軟骨代謝学会  2003 

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  • 結合組織成長因子CTGF/Hcs24の軟骨分化促進作用と細胞内シグナル伝達経路

    第16回日本軟骨代謝学会  2003 

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  • CCN familyに属するCyr61及びCTGF遺伝子の軟骨細胞株における協調的な遺伝子発現誘導と抑制

    第16回日本軟骨代謝学会  2003 

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  • AP1とCTGF/Hcs24/ecogeninとの相互作用の軟骨細胞肥大化における役割

    第20回日本骨代謝学会  2002 

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  • The roles of CTGF/Hcs24, a hypertrophic chondrocyte-specific gene producut 24, in skeletal development.

    1st Wittgenstein Conference:Genetics and Molecular Biology of Skeletal Development  2002 

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  • 硬組織発生過程でのerbB4の発現

    第44回歯科基礎医学会  2002 

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  • Two novel cis-acting elements of human CTGF/CCN2 gene expression.

    2nd International Workshop on The CCN Family of Gene  2002 

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  • 軟骨由来成長因子CTGF/Hcs24の細胞種特異的遺伝子発現抑制機構の解析

    第75回日本生化学会大会  2002 

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  • 肥大軟骨細胞由来CTGF/Hcs24はパールカンと相互作用し、軟骨細胞分化を促進する

    第75回日本生化学会大会  2002 

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  • 結合組織成長因子CTGF/Hcs24は細胞内で細胞骨格蛋白質と結合する

    第75回日本生化学会大会  2002 

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  • 肥大軟骨細胞特異的遺伝子産物CTGF/Hcs24のモジュール特異的抗体の解析とその軟骨細胞分化促進効果

    第44回歯科基礎医学会  2002 

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  • チロシンキナーゼ型レセプターErbB4遺伝子の軟骨細胞における発現

    第44回歯科基礎医学会  2002 

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  • Promoter activity determinant of human connective tissue growth factor (CTGF/Hcs24) gene in a human chondrocytic cell line, HCS-2/8.

    ASBMR 24rd Annual Meeting  2002 

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  • CTGF/Hcs24 induces chondrocytes differentiation through p38 mitogen-activated protein kinase (p38MAPK), and proliferation through p44/p42 MAPK/extracellular-signal regulated kinase (ERK).

    ASBMR 24rd Annual Meeting  2002 

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  • CTGF/Hcs24, a Hypertrophic chondrocyte-specific gene product, stimulates proliferation and differntiation but not hypertrophy of cultured articular.

    ASBMR 24rd Annual Meeting (Prenary Poster)  2002 

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  • 象牙質再生療法の開発-ヒト培養歯髄におけるCTGF刺激によるType I collagen, ALPの発現-

    第11回硬組織生物学会年会  2002 

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  • ヒト口腔扁平上皮癌細胞における結合組織成長因子(CTGF)の腫瘍細胞増殖抑制効果

    第44回歯科基礎医学会  2002 

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  • 結合組織CTGF/Hcs24遺伝子の軟骨由来細胞におけるグルココルチコイドによる発現誘導

    第44回歯科基礎医学会  2002 

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  • The role of CTGF/Hcs24 (connective tissue growth factor/hypertrophic chondrocyte specific gene product 24) in skeletal growth.

    MD Anderson Cancer Center Seminar, Texas University  2002 

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  • Effects of IL-1 beta and LPS on CTGF expression in mouse-derived odontoblast-like cells, MDPC-23.

    ASBMR 24rd Annual Meeting  2002 

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  • 軟骨由来の結合組織成長因子（CTGF/Hcs24）の脊椎動物間における3'-非翻訳領域の機能比較

    第20回日本骨代謝学会  2002 

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  • DNAマイクロアレイによるリウマチ性疾患病因遺伝子の解明

    第20回日本骨代謝学会  2002 

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  • 軟骨成長、血管新生に重 要な成長因子CTGF/Hcs24遺伝子の転写後調節エレメント、CAESARの作用機構

    第20回日本骨代謝学会  2002 

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  • Connective tissue growth factor (CTGF)の軟骨特異的な遺伝子発現を制御する新規シスエレメントTRENDIC

    第20回日本骨代謝学会  2002 

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  • 軟骨由来成長因子CTGF/Hcs24/ecogeninの構成モジュール特異的抗体の解析と軟骨細胞分化促進効果

    第20回日本骨代謝学会  2002 

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  • 軟骨細胞におけるチロシンキナーゼ型レセプターErbB4遺伝子の発現

    第43回日本生化学会中四国支部例会  2002 

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  • 抜歯後歯槽骨再生時における結合組織成長因子の発現

    第20回日本骨代謝学会  2002 

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  • 肥大軟骨細胞由来の成長因子CTGF/Hcs24のパラクリン作用はヘパラン硫酸の局在に依存する

    第20回日本骨代謝学会  2002 

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  • 結合組織成長因子CTGF/Hcs24/ecogeninの軟骨分化促進作用と細胞内シグナル伝達経路

    第20回日本骨代謝学会  2002 

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  • DNAマイクロアレイ(DNAチップ)によるリウマチ性疾患関連遺伝子の解明

    第75回日本生化学会大会  2002 

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  • マイクロアレイ法によるヒト間葉系幹細胞株の遺伝子発現プロファイルの解析

    第25回日本分子生物学会（ワークショップ）  2002 

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  • 結合組織成長因子CTGF/Hcs24のdexamethasoneによる誘導とそのメカニズム

    第25回日本分子生物学会年会  2002 

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  • Analysis of gene expression in osteoblastic cells stimulated by connective tissue growth factor, hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24).

    2nd International Workshop on The CCN Family of Gene  2002 

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  • Connective tissue growth factor induced by hypoxia may initiate angiogenesis in collaboration with matrix metalloproteinases.

    2nd International Workshop on The CCN Family of Gene  2002 

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  • ラット下顎枝骨折治癒過程の膜性骨化と内軟骨性骨化における結合組織成長因子(CTGF)の経時的発現

    第61回日本矯正歯科学会年次大会  2002 

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  • Protein kinase C mediates regulation of chondrocyte differentiation and proliferation of CTGF/Hcs24 via MAPK signaling.

    2nd International Workshop on The CCN Family of Gene  2002 

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  • Expression of connective tissue growth factor /hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24) during fracture healing.

    2nd International Workshop on The CCN Family of Gene  2002 

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  • Functional analysis of connective tissue growth factor (CTGF/CCN2) in calcifying tissues using transgenic mice and its functional correlation with bone-forming transcription factor CBFA1.

    2nd International Workshop on The CCN Family of Gene  2002 

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  • Ctgfプロモーター上に存在する新規シスエレメントTRENDICを介する制御とSmadシグナルとの関わり

    第25回日本分子生物学会年会  2002 

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  • DNAマイクロアレイによるリウマチ性疾患病因因子の解明

    第25回日本分子生物学会年会  2002 

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  • Immunolocalization and gene expression of CTGF in rat mandibular condylar cartilage.

    第50回国際歯科研究学会日本部会(JADR)総会・学術大会  2002 

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  • Analysis of gene expression profiles in human mesenchymal stem cells by using DNA microarray.

    The 12th Takeda Science Foundation Symposium on Bioscience  2002 

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  • The roles of CTGF/Hcs24, a hypertrophic chondrocyte-specific gene product 24, in cartilage, bone and vascular formation.

    2nd International Workshop on The CCN Family of Gene  2002 

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  • DNAマイクロアレイによる間葉系肝細胞の発現プロファイリング

    第44回歯科基礎医学会  2002 

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  • ３つのELISAシステムによるCTGF/Hcs24分子動態の解析

    第75回日本生化学会大会  2002 

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  • Expression of CTGF in endochondral and intramembranous ossification during mandibular fracture healing.

    IADR/AADR//CADR 80th General Session  2002 

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  • 骨軟骨組織修復における結合組織成長因子CTGF/Ecogeninの役割。

    第4回生体組織工学シンポジウム  2002 

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  • The AP-1-CTGF/Hcs24 interaction which may drive chondrocyte hypertrophy in growth cartilage.

    15th Annual Meeting of the Japanese Society of Cartilage and Metabolism  2002 

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  • 軟骨細胞においてヘパラン硫酸は肥 大軟骨細胞由来の成長因子CTGF/Hcs24の作用を制御する

    第15回日本軟骨代謝学会  2002 

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  • CTGF upregulation observed in the rat tooth extraction sockets.

    IADR/ AADR//CADR 80th General Session  2002 

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  • 軟骨細胞におけるチロシンキナーゼ型レセプター、ErbB4遺伝子の発現

    12回中国・四国骨代謝研究会  2002 

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  • 象牙質再生療法の開発-ヒト培養歯髄におけるCTGF刺激によるalkaline phosphataseの発現-

    第116回日本歯科保存学会 春期学会  2002 

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  • Connective tissue growth factor increased by hypoxia may initiate angiogenesis in collaboration with matrix metalloproteinases.

    12th International Vascular Biology Meeting  2002 

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  • 肺線維症における connectibe tissue growth factor (CTGF)の発現

    第46回日本リウマチ学会総会  2002 

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  • 顎関節ならびに膝関節の関節軟骨におけるCbfa1/Runx2遺伝子の発現

    第15回日本顎関節学会総会  2002 

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  • Effects of proinflammatory factors on CTGF expression in odontoblast-like cells.

    IADR/ AADR//CADR 80th General Session  2002 

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  • Immunohistochemical localization of connective tissue growth factor during reparative dentinogenesis.

    30th Annual Meeting of the AADR  2001 

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  • 軟骨由来の成長因子CTGF/Hcs24の軟骨細胞増殖分化促進作用におけるシグナル伝達機構の解析

    第14回日本軟骨代謝学会  2001 

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  • Suppressed Cbfa1 expression in prehypertrophic TMJ articular chondrocytes in vivo.

    30th Annual Meeting of the AADR  2001 

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  • Characterization of a Mouse ctgf3'-UTR Segment that Mediate Repressive Regulation of Gene Expression.

    第55回日本口腔外科学会総会  2001 

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  • 結合組織成長因子（CTGF/Hcs24）を応用した関節軟骨再生療法の可能性の検討-in vitro およびin vivoにおける検討-

    第３回生体組織工学シンポジウム  2001 

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  • チロシンキナーゼ型受容体ErbB4の軟骨組織における発現

    第14回日本軟骨代謝学会  2001 

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  • 肥大軟骨細胞由来成長因子CTGF/Hcs24の関節軟骨に対する作用

    第14回日本軟骨代謝学会  2001 

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  • Matricrine and MMPs. International Conference on New Strategres for the Treatment of Liver Cirrhosis

    2001 

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  • 軟骨由来の新規血管新生因子CTGF/Hcs24：その生理的・病理的意義。

    大阪府立成人病センター特別講演  2001 

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  • Chondrocyte apoptosis inmechanical-stress-induced OA cartilage of the rabbit TMJ.

    30th Annual Meeting of the AADR  2001 

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  • ニワトリ軟骨由来のCTGF/Hcs24cDNAのクローニングと解析

    第14回日本軟骨代謝学会  2001 

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  • マイクロアレイ解析によるリウマチ性疾患の病因遺伝子解明

    第9回日本分子生物学会年会  2001 

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  • 合組織成長因子(CTGF)の構造・機能解析のためのELISAシステムの開発

    第22回岡山歯学会学術集会  2001 

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  • 低酸素による結合組織成長因子(CTGF)及びマトメリクスメタロプロテアーゼ(MMP)活性の協調的発現誘導

    第9回日本血管細胞生物学会  2001 

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  • 軟骨細胞においてヘパラン硫酸は軟骨細胞由来成長因子CTGF/Hcs24の作用を制御する

    第74回日本生化学会大会  2001 

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  • 軟骨由来成長因子CTGF/Hcs24の遺伝子発現抑制機構

    第9回日本分子生物学会年会  2001 

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  • 結合組織成長因子CTGFの軟骨細胞特異的転写調節因子の探索

    第9回日本分子生物学会年会  2001 

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  • 結合組織成長因子(CTGF/hcs24)遺伝子3'-UTRの脊椎動物種間における抑制性制御作用の構造的・機能的比較

    第9回日本分子生物学会年会  2001 

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  • HTLV-・ TaxによるHSV-TKプロモーターの活性化：細胞種依存性とSp1の関与

    第9回日本分子生物学会年会  2001 

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  • 「ポストゲノム時代のリウマチ研究と運動器科学」マイクロアレイ解析によるリウマチ性疾患の病因遺伝子解明。

    日本分子生物学会年会ワークショップ  2001 

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  • 軟骨由来成長因子CTGFトランスジェニックマウスの硬組織形成と遺伝子発現の解析

    第43回歯科基礎医学会  2001 

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  • 軟骨由来成長因子CTGF/Hcs24遺伝子の転写後制御エレメントCAESARの構造と機能

    第43回歯科基礎医学会  2001 

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  • ヒト軟骨様細胞株HCS-2/8におけるCTGF/Hcs24遺伝子のプロモーター活性決定因子

    第43回歯科基礎医学会  2001 

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  • Promoter activity determinant of human connective tissue growth factor (CTGF/Hcs24) gene in a human chondrocytic cell line, HCS-2/8.

    ASBMR 23rd Annual Meeting  2001 

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  • 低酸素によるヒト乳癌細胞における結合組織成長因子CTGF及びマトメリクスメタロプロテアーゼの発現誘導

    第60回日本癌学会総会  2001 

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  • 癌抑制活性を有するヒト羊水および尿由来糖タンパク質Urinary trypsin inhibitor(UTI)の細胞膜結合部位の同定

    第60回日本癌学会総会  2001 

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  • マウス下顎頭軟骨におけるCbga1遺伝子の発現

    第43回歯科基礎医学会  2001 

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  • 軟骨様細胞株HCS-2/8における多機能成長因子CTGF/Hcs24の転写から分泌まで

    第74回日本生化学会大会  2001 

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  • 多機能成長因子CTGF/Hcs24遺伝子の転写後制御エレメント、CAESARの作用機序

    第74回日本生化学会大会  2001 

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  • Expression of connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24) during facture healing.

    SBMR 23rd Annual Meeting  2001 

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  • Mechanical stimulation induces CTGF expression in rat osteocytes.

    79th General Session of the IADR  2001 

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  • 結合組織成長因子CTGF/Hcs24の軟骨細胞様細胞株Hcs-2/8での発現と動態制御

    第33回日本結合組織学会  2001 

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  • In vitro及びIn vivoにおける肥大軟骨細胞由来の成長因子CTGF/Hcs24の関節軟骨細胞に対する作用

    第19回日本骨代謝学会  2001 

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  • CTGF/Hcs24軟骨強制発現トランスジェニックマウスの解析

    第19回日本骨代謝学会  2001 

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  • 肥大軟骨細胞由来の成長因子CTGF/Hcs24の内軟骨性骨化促進作用。

    第２２回日本炎症・再生医学会  2001 

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  • Effect of CTGF/Hcs24 on proliferation/differentiotion of articular chondrocytes in culture.

    79th General Session of the IADR  2001 

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  • 低酸素によるヒト乳癌細胞における結合組織成長因子CTGF及びマトメリクスメタロプロテアーゼ(MMP)活性の協調的発現誘導

    第43回歯科基礎医学会  2001 

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  • 軟骨由来成長因子CTGF/Hcs24のヒト軟骨細胞株Hcs-2/8におけるプロセシングと分泌の様態

    第19回日本骨代謝学会  2001 

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  • ヒト軟骨肉腫由来軟骨様細胞株Hcs-2/8における結合組織成長因子CTGF/Hcs24遺伝子のプロモーター活性決定因子

    第19回日本骨代謝学会  2001 

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  • 軟骨由来の成長因子(Connective tissue growth factor, CTGF/Hcs24)の軟骨細胞増殖，分化促進作用における情報伝達機構の解析

    第19回日本骨代謝学会  2001 

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  • Adenovirus-mediated CTGF gene delivery to cultured osteoblasts in vitro.

    30th Annual Meeting of the AADR  2001 

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  • ヒト軟骨細胞様培養細胞株HCS-2/8における結合組織成長因子ctgf/ecogeninのプロモーター活性決定因子

    第14回日本軟骨代謝学会  2001 

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  • Physiological Role of CTGF/Hcs24/Ecogenin, a Hypertyophic Chondrocyte- Specific Gene Prodact: Promotion of Endochondral Ossification by Acting on Chondrocytes, Vascular Endothelial Cells and Osteoblasts．

    第13回日本軟骨代謝学会  2000 

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  • 軟骨由来成長因子CTGF/Hcs24遺伝子の転写後調節エレメントCAESAR：変異体分析によって得られた新たな知見

    第23回日本分子生物学会年会  2000 

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  • 結合組織成長因子CTGF/Hcs24の軟骨分化促進作用におけるシグナル伝達経路の解析

    第59回日本矯正歯科学会  2000 

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  • Physiological roles of CTGF/Hcs24, a hypertrophic chondrocyte-specific gene product:promotion of endochondral ossification and angiogenesis.

    1st International Workshop on the CCN Familiy of Genes  2000 

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  • 慢性関節リウマチ関連抗原RA-A47の発現量減少による軟骨細胞障害作用

    第73回日本生化学会大会  2000 

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  • Characterization of a mouse ctgf 3'-UTR segment that mediate repressive regulation of gene expression.

    第23回日本分子生物学会年会  2000 

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  • ヒト軟骨細胞様培養細胞株HCS-2/8における結合組織成長因子ctgf/ecogenin遺伝子発現制御機構

    第23回日本分子生物学会年会  2000 

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  • 慢性関節リウマチ関連抗原RA-A47の発現量減少による軟骨細胞破壊とアポトーシスの誘導

    第23回日本分子生物学会年会  2000 

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  • 慢性関節リウマチ関連抗原RA-A47の発現レベルの低下にともなう細胞膜への局在変化とRA-A47の自己抗原としての認識機構

    第18回日本骨代謝学会  2000 

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  • 軟骨由来成長因子CTGF/HCS24による軟骨分化マーカーII型コラーゲンおよびX型コラーゲンの発現促進に対するMAPキナーゼ経路阻害剤の効果

    第18回日本骨代謝学会  2000 

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  • 軟骨由来の成長因子CTGF/Hcs24遺伝子に同定された新たな転写後制御エレメント、CAESAR

    第18回日本骨代謝学会  2000 

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  • A novel RNA element that confers post-transcriptionalrepression of human connective tissue growth factor/hypertrophoicchondrocyte specific 24 (ctgf/hcs24) gene.

    22nd Annual Meeting of the American Society for Bone and Mineral Research  2000 

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  • Molecular cloning and characterization of RA-A47, a rheumatoid arthritis-related antigen from a human chondrocytic cell line, HCS-2/8.

    22nd Annual Meeting of the American Society for Bone and Mineral Research  2000 

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  • 肥大軟骨由来の成長因子CTGF/Hcs24による細胞外基質構成タンパク質および細胞外基質分解酵素発現の制御

    第18回日本骨代謝学会  2000 

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  • 変形性関節症の骨棘形成における神経栄養因子とその受容体の発現

    第18回日本骨代謝学会  2000 

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  • 軟骨由来成長因子CTGF/Hcs24の関節軟骨における作用

    第73回日本生化学会大会  2000 

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  • 軟骨由来の成長因子CTGF/Hcs24遺伝子の転写後制御エレメント，CAESARの構造機能連関

    第73回日本生化学会大会  2000 

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  • 軟骨由来成長 因子CTGFと転写制御因子Cbfa1の発生過程での遺伝子発現のパターン解析

    歯科基礎医学会雑誌  2000 

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  • 軟骨由来成長因子Hcs24/CTGFの軟骨分化における役割とCbfalによるその発現制御

    第13回日本軟骨代謝学会  2000 

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  • ヒト軟骨肉腫由来軟骨細胞様細胞株HCS-2/8にお けるチロシンキナーゼファミリー遺伝子のクローニング

    第13回日本軟骨代謝学会  2000 

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  • 結合組織成長因子（CTGF/Hcs24）の骨軟骨組織再生作用-in vitroにおける検討-。

    第３回生体組織工学シンポジウム  2000 

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  • ヒト軟骨細胞様培養細胞株HCS-2/8におけるCTGF/Ecogenin遺伝子発現制御機構

    第13回日本軟骨代謝学会  2000 

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  • 導入したHSP70遺伝子の軟骨保護作用

    第13回日本軟骨代謝学会  2000 

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  • 慢性関節リウマチ関連抗原RA-A47の自己抗原としての認識機構：発現レベルの低下による細胞表面への局在

    第13回日本軟骨代謝学会  2000 

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  • 結合組織成長因子/肥大軟骨細胞特異的遺伝子産物（CTGF/Hcs24）発現による細胞周期変調効果

    第32回日本結合組織学会  2000 

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  • Gene delivery into chondrocytes by EBV-based episomal vector/cationic polymer complexes.

    Orthopaedic Research Society 46th Annual Meeting  2000 

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  • Ex vivo gene delivery by an adenovirus vector in treatment for cartilage defects.

    Orthopaedic Research Society 46th Annual Meeting  2000 

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  • Transduced HSP70 gene expression protects chondrocytes from stress.

    Orthopaedic Research Society 46th Annual Meeting  2000 

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  • 軟骨由来細胞株HCS-2/8細 胞におけるCTGFの動態

    第13回日本軟骨代謝学会  2000 

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  • Expression of neurotrophins and their receptors (TRK) during fracture healing.

    8th World Congress of the Societe Internationale de Recherche Orthopedique et de Traumatologie  1999 

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  • 慢性関節リウマチ(RA)の滑膜血管新生とCTGF

    第43回日本リウマチ学会総会・学術集会  1999 

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  • Expression of connective tissue growth factor (CTGF) in cartilaginous tumors.

    8th World Congress of the Societe Internationale de Recherche Orthopedique et de Traumatologie  1999 

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  • 軟骨欠損に対するアデノウイルスベクターを用いたex vivo遺伝子導入法

    第12回日本軟骨代謝学会  1999 

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  • 変形性関節症(OA)および慢性関節リウマチ(RA)関節軟骨における結合組織成長因子(CTGF)の局在。

    第12回日本軟骨代謝学会  1999 

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  • 内軟骨性骨化における軟骨由来成長因子Hcs24/CTGFの特異的受容体の変動

    第12回日本軟骨代謝学会  1999 

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  • Expression of connective tissue growth factor (CTGF) in cartilaginous tumors.

    21st World Congress of the Soclete Internatlonale de Chirurgle Orthopedique et de Traumatologie  1999 

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  • 軟骨性腫瘍における結合組織成長因子(CTGF)の発現

    日本整形外科学会  1999 

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  • 慢性関節リウマチ関連抗原RA-A47の全長構造と機能解析

    第12回日本軟骨代謝学会  1999 

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  • 軟骨細胞に対するDNA-Cationic Polymer複合体を用いた遺伝子導入法の検討

    第12回日本軟骨代謝学会  1999 

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  • 軟骨由来の成長因子Hcs24/CTGF(Ecogenin)の遺伝子発現調節メカニズム

    第17回日本骨代謝学会  1999 

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  • A cis-acting repressive element in the 3'-untranslated region of the CTGF gene.

    American Society for Bone and Mineral Research; 21st Annual Meeting  1999 

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  • 骨、軟骨の発生過程における軟骨由来成長因子CTGF/Hcs24の発現とCbfa1によるその制御

    第72回日本生化学会  1999 

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  • 骨芽細胞の増殖と分化に与える軟骨由来成長因子CTGF/Hcs24の作用

    第72回日本生化学会  1999 

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  • TNFαによるRA-A47の軟骨細胞内局在の変化と抗原提示

    第72回日本生化学会大会  1999 

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  • 軟骨由来の成長因子CTGF/Hcs24の細胞内での動態と機能

    第72回日本生化学会大会  1999 

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  • 慢性関節リウマチ関連抗原RA-A47は自己の発現レベルの低下にともない細胞膜へと局在が変化する

    第22回日本分子生物学会年会  1999 

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  • Cbfa1ノックアウトマウスにおける軟骨成長因子CTGF/Hcs24の発現とその制御様式

    第22回日本分子生物学会年会  1999 

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  • 骨折治癒過程における軟骨由来成長因子Hcs24/CTGFの発現-IN VIVO STUDY-

    第14回日本整形外科学会基礎学術集会  1999 

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  • 軟骨由来成長因子CTGF/Hcs24のマウス発生過程での遺伝子発現のパターン解析

    第41会歯科基礎医学会学術大会  1999 

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  • 軟骨成長因子CTGF/Hcs24の神経系における発現とその機能

    第41会歯科基礎医学会学術大会  1999 

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  • Regulation of trasduced gene expression in chondrocytes using HSP70 promoter.

    4th World Congress of the OsteoArthritis Research Society International  1999 

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  • Ex vivo gene delivery to cartilage defects.

    4th World Congress of the OsteoArthritis Research Society International  1999 

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  • 軟骨由来の成長因子CTGF/Hcs24の骨形成における役割。

    第52回日本細胞生物学会大会  1999 

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  • 骨芽細胞様細胞株MC3T3- E1のメカニカルストレスに対する応答性―神経栄養因子の役割―

    第17回日本骨代謝学会  1999 

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  • 慢性関節リウマチにおけるRA-A47の細胞内局在変化と抗原提示

    第41会歯科基礎医学会学術大会  1999 

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  • Physiological roles of connective tissue growth factor (CTGF/Hcs24): promotion of endochondral ossification, angiogenesis and tissue remodeling.

    The fourth International Symposium on Tissue Engineering for Therapeutic Use  1999 

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  • Transduced HSP70 gene protects chondrocytes from heat stress.

    4th World Congress of the OsteoArthritis Research Society International  1999 

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  • Gene delivery into chondrocytes by EBV-based episomal vector-polyamidoamin dendrimer complexes.

    4th World Congress of the OsteoArthritis Research Society International,  1999 

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  • マウス肋骨骨折モデルにおける軟骨由来成長因子Hcs24/CTGFの発現

    第17回日本骨代謝学会  1999 

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  • 軟骨由来成長因子Hcs24/CTGFのマウス胎生期における発現とCbfalによる制御

    第17回日本骨代謝学会  1999 

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  • 軟骨細胞の基質代謝におよぼす周期的メカニカルストレスの影響

    第12回日本顎関節学会総会  1999 

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  • ヒト結合組織成長因子(CTGF)cDNAの3'非翻訳領域(3'-UTR)による遺伝子発現抑制

    第31回日本結合組織学会学術大会  1999 

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  • 軟骨由来成長因子Hcs24/CTGFはヒト歯根膜由来線維芽細胞の増殖と分化を促進する

    第17回日本骨代謝学会  1999 

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  • マウス歯根膜細胞株(MPL)におけるニューロトロフィンとTRKレセプターの発現とその機能

    第17回日本骨代謝学会  1999 

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  • 軟骨由来成長因子Hcs24/ CTGFはヘパラン硫酸に結合し軟骨細胞の接着を促進する

    第17回日本骨代謝学会  1999 

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  • Effective regulation of;S-adenosylmethionie on chondrocyte differentiation via interstimulation of;polyamine production;gene expression of growth factors

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Awards

  • IADR Distinguished Scientist Award (Research in Oral Biology)

    2015  

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  • 平成25年度日本歯科医学会会長賞

    2014   日本歯科医学会  

    滝川正春

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    Country：Japan

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  • International CCN Society Scientific Award

    2012   International CCN Society  

    Takigawa, Masaharu

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  • 日本軟骨代謝学会賞

    2008   日本軟骨代謝学会  

    滝川正春

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    Country：Japan

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  • Scientific Award for the study of Bone and Joint Diseases (the Japan Rheumatism Foundation)

    1997  

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    Country：Japan

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  • Scientific Award (Japanese Society of Bone Metablism)

    1992  

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    Country：Japan

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Research Projects

  • Investigation on phase separation-mediated regulation of cell differentiation by droplet transpricptomics

    Grant number：24H00652  2024.04 - 2027.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    久保田 聡, 西田 崇, 服部 高子, 高江洲 かずみ, 滝川 正春, 青山 絵理子, 大野 充昭

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    Grant amount：\48100000 （ Direct expense: \37000000 、 Indirect expense：\11100000 ）

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  • Development of dropletomics that clarifies transcriptional regulation under liquid-liquid phase separation

    Grant number：23K17439  2023.06 - 2027.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Pioneering)

    久保田 聡, 西田 崇, 服部 高子, 高江洲 かずみ, 滝川 正春, 青山 絵理子, 大野 充昭

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    Grant amount：\25740000 （ Direct expense: \19800000 、 Indirect expense：\5940000 ）

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  • Pioneering chondroneutrigenomics research and its development into chondroneutrigenetics

    Grant number：20K20611  2020.07 - 2024.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Pioneering)

    滝川 正春, 青山 絵理子, 星島 光博, 久保田 聡, 西田 崇, 江口 傑徳

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    Grant amount：\25870000 （ Direct expense: \19900000 、 Indirect expense：\5970000 ）

    1．昨年度メチオニンの代謝産物であるS-アデノシルメチオニン(SAM)をヒト軟骨細胞様細胞株HCS-2/8の培養系に添加すると、まずCCN2の遺伝子発現が亢進し、次いで2型コラーゲンの遺伝子発現が上昇し、その後、アグリカンの蓄積量（アルシアンブルー染色）も増加すること、また、ポリアミンの前駆体の一つSAM脱炭酸物を合成するSAM 炭酸酵素AMD1の阻害剤、SardomizideをSAMと共に添加するとSAMによるアグリカンの蓄積が抑制されることを見いだした。今年度はこれらの知見を、染色の場合は生化学的手法で測定するなど他の手法を用いて再確認するとともに、1培養細胞株では不十分との考えのもと、ラット軟骨肉腫由来の軟骨細胞様細胞株RCS細胞を用いて確認した。これらの結果はSAMがCCN2の発現を誘導する機能分子であることを示している。また、同培養系にSAMを添加して、スペルミジン、スペルミン等のポリアミンレベルをHPLCで測定すると、両ポリアミン濃度の増加が見られた。従って、SAMは少なくとも一部はポリアミン合成を介して軟骨細胞の分化機能を亢進させることを示唆している。
    2．CCN2が関節軟骨形成因子GDF5と結合することはすでに報告済みであるが、CCN2はGDF5とBMPRIｂとの結合には影響しないこと、NogginはCCN2のGDF5への結合を阻害することを見いだした。また、CCN2は、軟骨細胞においてGDF5によるSmad1/5/8のリン酸化を増強し、アグリカン遺伝子発現促進作用をさらに増強した。
    3．齧歯類の変形性関節症の予防・修復作用を有するCCN2と「陰と陽」の関係があるとされているCCN3の発現が、ヒト変形性肩関節症および変形性股関節症の症状と正に相関することを明らかにした。2と3の知見は本課題後半のコンドロニュートリジェネティクス研究に繋がる重要な基礎的知見となる。

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  • Intracellular function and new extracellular signaling pathways of CCN proteins and their common molecular base

    Grant number：19H03817  2019.04 - 2023.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    滝川 正春, 青山 絵理子, 星島 光博, 久保田 聡, 西田 崇, 江口 傑徳, 大野 充昭, 鈴木 守

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    Grant amount：\17290000 （ Direct expense: \13300000 、 Indirect expense：\3990000 ）

    １．CCNタンパク質の意外な新機能（細胞内機能）：CCN2はN末にシグナルペプチド(SP)を有する分泌性タンパク質であるが、その分子内に塩基性アミノ酸に富んだ核移行シグナル様の配列を持ち、核内タンパク質として機能する可能性が考えられる。そこで、SPを除いたCcn2および全長Ccn2を組み込んだCCN2発現プラスミドをNIH3T3細胞に遺伝子導入し、CCN2の核移行を調べたところ、SPの有無に関わらず、CCN2が線維芽細胞の核内に移行することを見いだした。また、核内に移行したCCN2は、YAPと結合し、CCN2のプロモーター上、あるいは線維症に関連するPU.1のプロモーター上に結合し、CCN2やPU.1の発現を亢進させ、筋線維芽細胞のマーカーであるαSMAの遺伝子発現レベルを亢進させた。これらの結果は、従来の線維症発症おけるCCN2の作用は、オートクリン・パラクリン作用とされてきたが、イントラクリン作用も関与していることを示唆している。
    2．CCNタンパク質の細胞外新情報ネットワーク：CCN1,CCN2,CCN3が前立腺がん細胞株PC-3細胞の培養上清から分離した細胞外ベシクル(EV)にこの量的順序で存在すること、CCN4-6は存在しないことを、LC-MS/MSを使ったプロテオーム解析で明らかにした。また、ヒト軟骨細胞株HCS-2/8の培養上清を用いて、全長CCN2がEVに搭載されて遠隔組織に運ばれ、MMPにより切断され、EVからCCN2フラグメントが遊離して作用する新情報ネットワークの存在を示唆した。
    3．構造ー機能解析に関しては、CCN2とCDMP1/GDF-5が結合することを見いだした。立体構造解析については、CCN2の結晶化には未だ至っていない。
    これらの代表例を含めCCN関連で、学術論文3報を出版し、10報をin press, 編著本1冊をin pressとした。

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  • Neutrigenomics studies on endochondral ossification and articular cartilage mainteinance/regeneration

    Grant number：17K19757  2017.06 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Exploratory)

    TAKIGAWA Masaharu

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    Grant amount：\6500000 （ Direct expense: \5000000 、 Indirect expense：\1500000 ）

    In this study we found the followings. (1) Glucose and its metabolite methyglyoxal regulated gene expression of endochondral ossification genetic factor CCN2 and articular cartilage maintenance factor CCN3 in chondrocytic HCS-2/8 cells. (2) A tryptophan metabolite serotonin regulated gene expression of CCN2 in chondrocytes and another metabolite melatonin was involved in cartilage growth and development. (3) CCN2 mediated not only low-intensity pulsed ultrasound (LIPUS)-stimulated expression of the differentiated phenotype of chondrocytes, but also LIPUS-inhibited adipocyte differentiation of undifferentiated mesenchymal stem cells, showing that gene expression of CCN2 could be an important target and marker of cartilage nutrigenomics.

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  • Establishment of molecular basis of CCN family proteins for therapeutic use and its related translational research

    Grant number：15H05014  2015.04 - 2018.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    TAKIGAWA Masaharu, SHIMO Tsuyoshi, ONO Mitsuaki, HOSHIJIMA Mitsuhiro, NAGAOKA Noriyuki, FURUMATSU Takayuki

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    Grant amount：\17030000 （ Direct expense: \13100000 、 Indirect expense：\3930000 ）

    As a function-specific receptor for CCN proteins, we identified a growth-specific receptor for CCN2. Among 4 individual modules of CCN2, IGFBP and TSP1 modules showed angiogenesis activity. IGFBP-TSP1 dual module-connected recombinant protein showed strong angiogenesis activity. The TSP1 module also showed fibrogenic activity. Low Intensity Pulsed Ultra Sound (LIPUS) increased expression of ECM components such as aggrecan and collagen type II in chondrocytes through induction of CCN2 production. This function of LIPUS was mediated through a Ca ion channel TRPV4. In addition, we found that CCN3 protected progression of osteoarthiritis in an animal model and that CCN4 promoted chondrogenic differentiation of bone marrow-derived mesenchymal stem cells.

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  • ＣＣＮ２個別モジュールの機能解明と変形性関節症治療薬開発に向けた橋渡し研究

    Grant number：14F04420  2014.04 - 2017.03

    日本学術振興会  科学研究費助成事業  特別研究員奨励費

    滝川 正春, ABD EL, KADER TAREK

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    Authorship：Principal investigator 

    Grant amount：\2300000 （ Direct expense: \2300000 ）

    １）鶏卵をシャーレに取り出しインキュベータ内で、鶏胚を発育させその漿尿膜(CAM)にサンプルをアプライして血管新生活性を測定するex ovo CAM assayの結果の判定が評価者の目視による判定では安定しないので、シャーレでインキュベートした鶏卵のCAMの写真を計時的に撮影し、その画像をコンピューター解析して、新生血管を定量的に測定するアッセイ系を開発した。
    ２）この新規に開発したアッセイ系を用いて、IGFBPモジュールは投与後24時間と早い時期に血管新生を強く誘導すること、一方、TSP1モジュールはこれよりも遅く48～72時間後に同程度の効果を示すことが明らかになった。
    ３）IGFBPモジュールが軟骨培養細胞のプロテオグリカン合成を強く促進し、血管内皮細胞による管腔形成促進作用も強く、ex ovo血管新生作用も短時間でみられることから、これに細胞外基質へのretention作用の強いTSP1モジュールを結合させたIGFBP―TSPモジュール結合体は、super cartilage regeneration作用やsuper angiogenesis作用が期待され、昨年度、この組み換え体タンパク質を調整した。本年度、これを用いたin vivoならびにex vivo実験を行う予定であったが、組み換え体タンパク質を調製する際に使用した溶媒が、生体に対して異害作用を示す（溶媒だけで鶏卵が死亡する）ことが判明して、溶媒を生理食塩水等の異害作用のない溶媒に変更することを種々試みたが、沈殿してしまい、最終年度の５ヶ月という期間内には、super active CCN2 誘導体と予想されるこのCCN2誘導体の生物作用のアッセイまでは至らなかった。生体投与実験の際には培養系に比べ、多量のCCN2を必要とするため、どうしても持ち込む溶媒量も増え異害作用が出てしまうので、この点は今後解決しなければならない重要な課題である。

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  • The presence and its significance of non-canonical action of decoy receptors

    Grant number：26670808  2014.04 - 2016.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    TAKIGAWA MASAHARU, KUBOTA SATOSHI, AOYAMA ERIKO, NISHIDA TAKASHI, HATTORI TAKAKO, TAKAESU KAZUMI

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    Grant amount：\3640000 （ Direct expense: \2800000 、 Indirect expense：\840000 ）

    In this study, we proposed a new concept showing the presence and its significance of non-canonical action of decoy receptor (-like) molecules by demonstrating 2 examples. 1) Osteoprotegerin (OPG) bound to CCN family protein 2 (CCN2), which binds to RANK and positively regulates RALK signaling, thereby inhibiting osteoclastogenesis via RANK signaling. 2) Platelet-derived growth factor receptor-like (PDGFRL) did not bind to PDGF which is the ligand for PDGF. Instead, PDGFRL did bind to CCN2 which plays important roles in chondrogenesis and endochondral ossification and another member of CCN family CCN3. These findings suggest that PDGFRL plays an important role in the cartilage biology, possibly by regulating the molecular behavior of CCN2. 3) We also found that c-type lectin receptor CD302 bound to CCN2, suggesting possible discovery of another example which supports our new concept.

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  • 軟骨細胞分化の運命決定と関節防御ーＣＣＮ３分子機能の新局面

    Grant number：13F03412  2013.04 - 2016.03

    日本学術振興会  科学研究費助成事業  特別研究員奨励費

    滝川 正春, JANUNE DANILO

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    Authorship：Principal investigator 

    Grant amount：\2200000 （ Direct expense: \2200000 ）

    １）CCN3の過剰発現がラット初代関節軟骨細胞の単層培養系で分化形質の発現を促進したので､関節軟骨ペレット培養系でもこの点を確認した。その結果、ペレットがCCN3過剰発現細胞では対照に比べやや大きくなり、組織標本を作製してトルイジンブルー染色を行うと、CCN3過剰発現ペレットでは対照に比べ、濃く染色されその領域も広かった。即ち、CCN3過剰発現でin vitroでの軟骨形成の促進がみられた。
    ２）ヒト組み換えGST-CCN3タンパク質とその対照としてのヒト組み換えGSTタンパク質を徐放剤としてのgelatin hydrogelに吸着させ、ラット膝関節腔に投与し、その1日後にモノヨード酢酸（MIA）を同ラット膝関節に投与して、変形性関節症を誘発したところ、ヒト組み換えGST-CCN3タンパク質前投与群ではMIAによる関節軟骨のプロテオグリカンの分解が抑えられていることがトルイジンブルー染色で確認できた。また、tidemarkのintegrityも、GST-CCN3タンパク質の投与群では、対照のMIA単独処置群に比べ高かった。さらに、関節軟骨表層のマーカー分子であるlubricinは、MIA投与により変形性関節症を誘発すると消失するのに対し、CCN3タンパク質を前投与することにより、この消失が防御でき、lubricinが関節表層を綺麗に覆っていることが免疫染色で観察できた。すなわち、CCN3は関節軟骨の分化形質を促進する作用を有し、MIA誘導性実験的変形性関節症を防御する作用があることが明らかとなった。
    以上の結果は、前年度および前々年度に報告した結果と併せて一つの論文に纏めて、国際誌に投稿し、現在revise中である。

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  • Elucidation of molecular basis of CCN family action as masterminds and its medical application

    Grant number：24390415  2012.04 - 2015.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    TAKIGAWA MASAHARU, KUBOTA Satoshi, HATTORI Takako, NISHIDA Takashi, AOYAMA Eriko

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    Grant amount：\18200000 （ Direct expense: \14000000 、 Indirect expense：\4200000 ）

    We elucidated molecular mechanism of actions of CCN family proteins as masterminds by investigating physical interactions between CCN proteins and various molecules such as growth factors and their receptors, and by determining their final biological outcome in various cultured cells. We also generated transgenic mice overexpressing CCN2 in cartilage and found harmonized promotion of endochondral ossification in the TG mice, which would be a proof of function of a mastermind. Moreover, TSP-1 module among 4 independent modules of CCN2 had more potent action than that of full length CCN2 in cartilage regeneration in experimental osteoarthritis animal models, suggesting possible medical application of a CCN2 fragment for regenerative medicine for skeletal tissues. Furthermore, low intensity pulsed ultrasound induced gene expression of CCN2, aggrecan and collagen type II in chondrocytes, suggesting possible non-invasive application of CCN2 for cartilage regeneration in osteoarthritis.

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  • Comprehensive study on molecular basis of actions of CCN family proteins as novel signal conductors and its translational application

    Grant number：19109008  2007 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (S)

    TAKIGAWA Masaharu, KUBOTA Satoshi, HATTORI Takako, NISHIDA Takashi, AOYAMA Eriko

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    Grant amount：\110500000 （ Direct expense: \85000000 、 Indirect expense：\25500000 ）

    We have established a novel concept that CCN family proteins should be considered a newly classified signaling molecules that comprehensively regulate extracellular signals, and thus should be entitled "Signal Conductors." Moreover, we have accumulated basic data for application of CCN proteins toward harmonized regenerative medicine and for therapeutics of diseases with their abnormal upregulation, leading to their medical applications.

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  • The role of CTGF as a novel tissue-regenerating factor, regenerin, and its application for medical and dental tissue engineering

    Grant number：15109010  2003 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (S)

    TAKIGAWA Masaharu, KUBOTA Satoshi, HATTORI Takako, NISHIDA Takashi, YAMAMOTO Teruko, TABATA Yasuhiko

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    Grant amount：\103870000 （ Direct expense: \79900000 、 Indirect expense：\23970000 ）

    1. Using wild type and/or mutant animals, we found that in addition to endochondral ossification in growth plate, CTGF/CCN2 was involved in secondary ossification center formation, intramembranous ossification, formation of periodontal ligament and articular and auricular cartilages, distraction osteogenesis and repair of tooth extraction socket. In vivo administration of CTGF/CCN2 with gelatin hydrogel into the artificial defect of articular cartilage and bone resulted in repair of these tissues, respectively. Taken together with the finding that platelets contained much CTGF/CCN2, these findings indicate that CTGF/CCN2 functions as a regeneration factor "regenerin".
    2. We developed CTGF/CCN2 domain-specific antibodies and domain-specific ELISA systems. The function and signal transduction pathway of each domain was different depending on types of cells, such as chondrocytes and endothelial cells. CT domain of CTGF/CCN2 promoted adhesion of mesenchymal stem cells on hydroxyapatite plates, suggesting a possible application for bone regeneration with a combination of CTGF/CCN2 and hydroxyapatite.
    3. A cis-element in 3'-untranslation region (3'-UTR) of CTGF/CCN2 mRNA, which was involved in destabilization of its mRNA, and a protein, which bound to the element, were found in chondrocytes. The biding between them changed in reverse relation to the process of chondrocyte differentiation. A hypoxia-inducible protein, which stabilized CTGF/CCN2 mRNA by binding to its 3'-UTR was also detected.
    4. CTGF/CCN2 bound to perlecan, aggrecan and fibronectin, indicating its retention in extracellular matrix. CTGF/CCN2 had collaborative action with M-CSF on cartilage. Low density lipoprotein-related protein I was one of the receptors for CTGF/CCN2 in chondrocytes. Concerning signal transduction pathway of CTGF/CCN2 in chondrocytes, PKC was found as an upstream mediator of ERK and p38MAPK. JNK was involved in cell proliferation. PI3K and PKB were found to be involved in calcification.

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  • Functional analysis of the cartilage-derived multifunctional growth factor ecogenin/CTGF by using mutant animals

    Grant number：13307053  2001 - 2002

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    TAKIGAWA Masaharu, NAKANISHI Tohru, KUBOTA Satoshi, YAMAAI Tomoichirou, KIMURA Tomoatsu, KOMORI Toshifumi

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    Grant amount：\37050000 （ Direct expense: \28500000 、 Indirect expense：\8550000 ）

    1) We established transgenic mice that overproduce ecogenin/CTGF under the control of mouse type IX collagen promoter. The mice showed dwarfism and decreases bone density. The expression of ctgf was completely abolished in cbfal -nul I mice, ctgf-transgenic mice rescued the cartilage differentiation of cbfal-null mice.
    2) We examined the phenotype of ctgf null mice provided in collaboration with K. Layons and found that they had the disorders of not only endochondral ossification but also tooth development.
    3) Ecogenin/CTGF promoted proliferation and proteogycan synthesis of articular chondrocytes but did not promote their hypertrophy. It also repaired articular cartilage defect without calcification. Ecogenin/CTGF induced chondrocyte differentiation though p38 MAPK, and chondrocyte proliferation through ERK. Perlecan was essential for the paracrine action of ecogenin/CTGF on chondrocytes. Moreover, ecogenin/CTGF was found to bind actin and to induce apoptosis when overexpressed, suggesting intracellular function. Therefore, the high level of gene expression of ecogenin/CTGF in hypertrophic chondrocytes may be related to their cell death at the end of endochondral ossification, in addition to the role as a paracrine factor. We also found tahat ecogenin/CTGF is one of hypoxia-induced angiogenesis factors. We also found cis-element which regulates ecogenin/CTGF in chondrocytes.
    4) Expression of ecogenin/CTGF was observed in not only in hypertrophic chpndrcoyes but also in osteoblas and pre-osteoblats during fracture healing. Its gene expression was also observed in osteoblasts during alveolar bone regeneration after tooth extraction. Mechanical stress induced gene expression of ecogenin/CTGF in osteoblasts and osteocytes.
    These findings indicates that ecogenin/CTGF is a multifunctional growth factor which play important roles in endochondral ossification, intramembranous ossification, tooth development, maintainance and repair of articular cartilage and bone remodeling.

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  • 軟骨成長・アンチエイジング因子CCN2の健康維持への応用に向けた分子基盤の解明

    Grant number：25K03047  2025.04 - 2028.03

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    滝川 正春

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    Grant amount：\18850000 （ Direct expense: \14500000 、 Indirect expense：\4350000 ）

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  • 糖代謝障害が招く軟骨肥大性細胞老化を介したO Aの発症機構の解明とC C N２の役割

    Grant number：24K12869  2024.04 - 2027.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    西田 崇, 服部 高子, 青山 絵理子, 高江洲 かずみ, 滝川 正春, 久保田 聡

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

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  • Intracellular proteostatic function of CCN2 in chondrocytes during endochondral ossification

    Grant number：23K09352  2023.04 - 2026.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    村瀬 友里香, 滝川 正春, 久保田 聡, 青山 絵理子

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

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  • S-アデノシルメチオニンによる軟骨基質産生の新制御機構の解明―ポリアミンを中心に

    Grant number：22K09902  2022.04 - 2025.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    青山 絵理子, 滝川 正春, 久保田 聡

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    Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）

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  • 象牙芽細胞の表面に突き出た細胞小器官の機能解析と象牙質再生への応用

    Grant number：22K10075  2022.04 - 2025.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    高江洲 かずみ, 服部 高子, 青山 絵理子, 滝川 正春, 西田 崇, 久保田 聡

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    Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）

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  • 非コードRNAを介した新たな軟骨ホメオスタシスとその変性メカニズムの解明

    Grant number：22K10218  2022.04 - 2025.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    森谷 徳文, 滝川 正春, 久保田 聡, 服部 高子, 西田 崇, 近藤 星

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    Grant amount：\4160000 （ Direct expense: \3200000 、 Indirect expense：\960000 ）

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  • Inverse genetics: A new methodology for the identification of key genes of somatic cell differentiation

    Grant number：21K19603  2021.07 - 2023.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Exploratory)

    久保田 聡, 西田 崇, 服部 高子, 高江洲 かずみ, 青山 絵理子, 滝川 正春, 大野 充昭

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    Grant amount：\6500000 （ Direct expense: \5000000 、 Indirect expense：\1500000 ）

    初年度である本年度は、本研究で提唱する「インバース・ジェネティクス方法論」を、軟骨細胞を用いて検証することを第一の目的と定め研究を進めた。当初の予定ではマウス肋軟骨細胞を用いる予定であったが、長鎖非コードRNA (lncRNA) 遺伝子の数がはるかに多いこと、およびフィーダー細胞としてマウス由来SNL細胞を使うことを考慮しヒト軟骨細胞を用いた検討から開始することとした。理論上は可能だが軟骨細胞からiPS細胞を作成できたという報告はまだない。したがってまず山中４因子 (OSKM) を強制発現するレンチウイルスベクターを作成し、ヒト軟骨細胞に導入、リプログラミングが起こるかどうかをコロニー形成を指標に検討した。その結果OSKM導入発現２週間後には多数のコロニーの形成が見られ、軟骨細胞もiPS細胞化しうることが確認された。この結果を受けて、iPS干渉法によって仮説の妥当性とSOX9遺伝子の軟骨細胞分化の機能確認に進んだ。すなわち軟骨細胞にOSKMに加えてSOX9を発現させることでリプログラミングが阻止されるかを検証した。その結果SOX9発現によって形成されるコロニーは減少したがゼロにはならなかった。これはSOX9が単独で軟骨細胞分化を決定しているのではないためと考えている。そして次にシングルセル解析に進むにあたっては、解析前にフィーダー細胞を除去する必要がある。そのため以上の研究に並行して、蛍光色素mCherryを発現するSNL細胞を新たに樹立し、フローサイトメトリーで除去するシステムを整えてきた。ここまでは順調であったが、この実験システムではリプログラミング効率が十分ではなく、シングルセル解析で有意な結果を得るために必要なOSKM導入細胞数の確保が難しいことが分かってきた。そこで最近開発された一体型山中因子発現ウイルスベクターを試したところ、予備実験で飛躍的に高い導入効率が得られた。来年度はこのシステムを用いて研究を先に進める予定である。

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  • Regulation of skeletogenesis by long noncoding RNAs through CCN2

    Grant number：23K21483  2021.04 - 2025.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    久保田 聡, 服部 高子, 青山 絵理子, 高江洲 かずみ, 滝川 正春, 西田 崇

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    Grant amount：\17160000 （ Direct expense: \13200000 、 Indirect expense：\3960000 ）

    1. ACURの機能解析：ACURはCCN2 mRNAの3'非翻訳領域に相補的なアンチセンスRNAであり、その発現が予想に反してCCN2 mRNAの発現量と相関する。本年度は昨年度から取り組んでいる、GapmeRを用いたACUR特異的サイレンシング実験を繰り返し、ACURサイレンシングによりCCN2 mRNAの発現が有意に低下すること、さらに軟骨細胞分化のマスター転写因子であるSOX9の発現も同様に抑制されることを明らかにした。この効果はCCN2に対してより強くみられるため、ACURはCCN2の遺伝子発現促進を通じて軟骨細胞分化に貢献している可能性が高くなった。
    2. ACURによるCCN2発現制御メカニズムの解析：ACURのCCN2制御機構を明らかにするため、CCN2 3'-UTRを蛍ルシフェラーゼ遺伝子下流に接続したレポーターベクターを軟骨細胞様HCS-2/8細胞に、ACUR強制発現ベクターとともに導入してルシフェラーゼ活性を評価したが、ACUR発現による変化はみられなかった。よってCCN2 3'-UTRを標的とするmiRNAなどのアクセスを遮断してCCN2発現を増強するという可能性は低くなった。そこで次にACURがCCN2遺伝子座周辺の微細環境の形成に貢献していることを想定し、予備実験を開始した。
    3. UCA1の作用メカニズムの解明：昨年度の研究でUCA1の作用が軟骨細胞特異的であることが明らかになったが、本年度はヒト線維芽細胞にUCA1を強制発現させ、RNA-sequencingを行ったデータを公共データベースからダウンロードし再解析した。その結果、線維芽細胞でUCA1はCCN2発現に影響を与えないという結果が得られた。したがってUCA1によるCCN2発現制御は軟骨細胞形質の変化に伴う間接的な現象と考えられる。
    4. CCN2遺伝子座から出力される新たなRNA分子の発見：CCN2 pre-mRNAから生成しうる環状RNA (circRNA)を探索したところ、ヒトとマウスにおいて今までに報告のないcircRNAが複数出力されていることを見出した。

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  • CCN２の転写因子様機能を介した線維症のキープレイヤー筋線維芽細胞分化機構の解明

    Grant number：20K09889  2020.04 - 2023.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    西田 崇, 滝川 正春, 久保田 聡, 服部 高子, 青山 絵理子, 高江洲 かずみ

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    Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）

    線維性疾患のキープレイヤーである筋線維芽細胞はI型コラーゲンやαSMAを産生することが知られているが、その分化メカニズムは未だ明らかにされていない。本研究課題は筋線維芽細胞の分化にCellular communication network factor 2 (CCN2)が関わっているのか、そしてどのように関わっているのかを明らかにすることである。当該年度では、マウス線維芽細胞株NIH3T3細胞にCCN2を過剰発現させた時の筋線維芽細胞への分化に対する影響を解析した。以下にその結果を示す。
    1.シグナルペプチドを欠失したCCN2発現プラスミド(Sp-Ccn2)あるいはシグナルペプチドを付加したCCN2発現プラスミド(Sp+Ccn2)をNIH3T3細胞に遺伝子導入した結果、シグナルペプチドの有無に関わらず、一部のCCN2は核内に認められた。
    2.Sp-Ccn2あるいはSp+Ccn2プラスミドを遺伝子導入したNIH3T3細胞からtotal RNAを抽出し、筋線維芽細胞分化に重要な転写因子であるPU.1 (Spi1)の遺伝子発現レベルを定量RT-PCRで調べた結果、Sp-Ccn2を遺伝子導入した群ではempty vector (EV)を導入した群と変わらなかったが、Sp+Ccn2を遺伝子導入した群はSpi1の遺伝子発現レベルが有意に上昇した。また、Sp+Ccn2を遺伝子導入した群ではEVを導入した群と比較して、αSMAの遺伝子発現レベルが有意に上昇した。
    3.転写共役因子YAPとCCN2が結合することを免疫沈降-Western blot法で確認した。
    4.Sp+Ccn2を遺伝子導入後、抗CCN2抗体でクロマチン免疫沈降し、CCN2及びPU.1のプロモーター領域のプライマーを用いてPCRを行った結果、CCN2及びPU.1共にバンドが検出された。

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  • Regulation of CCN2 by an endogenous UTR blocker and its biological significance

    Grant number：19K22716  2019.06 - 2021.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Exploratory)

    Kubota Satoshi

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    Grant amount：\6370000 （ Direct expense: \4900000 、 Indirect expense：\1470000 ）

    The CCN2 gene is expressed in chondrocytes and plays a critical role in mammalian skeletal development. The aim of this study is to clarify the function of a novel lncRNA entitled ACUR that covers the entire 3'-untranslated region of the CCN2 mRNA. First, we found that ACUR was expressed, not only in several types of cancer cells, but also in human chondrocytic cells and chondrocytes isolated from knee joints. ACUR expression was subsequently confirmed in a murine mesenchymal stem cell-like cells, which was repressed along with adipogenic differentiation. Interestingly, CCN2 mRNA expression was decreased upon adipogenic differentiation as well. ACUR was also detected in murine chondroblastic cells. However, in contrast, ACUR expression was increased during the course of chondrocytic differentiation. These findings indicate that ACUR is conserved between human and murine species and that this lncRNA contributes to chodrocytic differentiation, positively regulating the CCN2 gene.

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  • CD302の新機能：破骨細胞の分化制御とその機構及び骨・軟骨代謝研究への展開

    Grant number：19K10053  2019.04 - 2023.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    青山 絵理子, 滝川 正春, 久保田 聡

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    Grant amount：\4420000 （ Direct expense: \3400000 、 Indirect expense：\1020000 ）

    これまでに軟骨細胞および骨芽細胞におけるCD302の発現と細胞密度による発現の変化について示してきたが、この研究をさらに進めてるCD302の発現の抑制が骨芽細胞にどのような影響をもたらすかについて 解析したところ、細胞数が顕著に減少した。この結果を受けてCD302抑制細胞におけるアポトーシスについて調べるためCaspase3/7の活性化を指標として検証したところ、CD302発現抑制細胞群ではアポトーシス陽性細胞率が上昇していることが分かった。このことからCD302発現抑制による細胞数の減少はアポトーシスの誘導がその原因の一つであると考えられる。そこでCD302と細胞死に関してさらに詳細に調べるため細胞内のシグナル伝達経路に着目し、CD302発現抑制細胞群では無処理細胞群に比べて細胞内でのFAKおよびAktのリン酸化が低下していることを明らかにした。Aktは細胞生存シグナルと呼ばれており、FAKは細胞接着刺激によって活性化することが知られている因子である。この結果はCD302が細胞接着に何らかの形で寄与していることを示唆している。さらに、acetyl-alpha tubulinの細胞蛍光免疫染色によりCD302の発現を抑制した細胞群において一次繊毛形成が如実に減少していることが分かった。CD302がどのような分子を介してこれらの現象を引き起こしているのかについて探求するため、各種のデータベースを用いてCD302と関連が示唆されている分子について調査したところ、FNDC9 (Fibronectin Type III Domain Containing 9)およびARL13Bと結合する可能性があることが分かった。前者は細胞接着に関する因子であり、後者は一次繊毛に局在し、その指標ともされている因子の一つである。今後はこれらの因子とCD302の関わりを明らかにする予定である。

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  • 細胞アンテナによる象牙質再生への道を拓く基礎研究

    Grant number：19K10109  2019.04 - 2023.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    高江洲 かずみ, 服部 高子, 青山 絵理子, 滝川 正春, 西田 崇, 久保田 聡

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    Grant amount：\4420000 （ Direct expense: \3400000 、 Indirect expense：\1020000 ）

    日本人において伸び悩んでいる健康寿命の延長には咀嚼機能維持が鍵となり、歯の再生が望まれる。しかしながら、歯の再建に必須である象牙質再生は自然状態では充分に行われない。
    このため、象牙芽細胞の細胞アンテナ〝一次繊毛"の形成や細胞周期制御に機能するIntraflagellar transport (Ift) 88の機能制御により、理想的な形質・形態の象牙質の再生を目指すべく、まずは正常象牙質の形成過程である1. 象牙芽前駆細胞の接着・増殖、2. 分化、3. 細胞極性の分子制御機構の検討を行っている。
    現在までに、IFT88は一次繊毛形成に働き、一次繊毛関連シグナルの一つである古典的WNTシグナルの抑制を介して象牙芽細胞分化を制御すること、また、古典的WNTシグナルは一次繊毛形成を抑制することを明らかにし、一次繊毛と古典的WNTシグナルの間にはネガティブフィードバックが存在することを示唆した（国際雑誌Boneへの掲載）。
    また、細胞接着能力や細胞増殖速度への影響をも検討しており、現在までに、Ift88をノックダウンしたラット象牙芽前駆細胞であるsh-Ift88 KN-3細胞では、一次繊毛形成に関係なく、抑制されることを確認している。本年度は、この制御機構を探索するために、ArrayScan VTI HCS Reader (Thermo Fisher Scientific Inc)を用いて、細胞増殖抑制に機能するHippoシグナル伝達経路の転写共役因子YAPの核移行をKN-3細胞とラット乳癌細胞株MRMT-1細胞と比較、検討を行った。その結果、Ift88をノックダウンしたMRMT-1細胞においては、現在までの報告通り、YAPが核移行する細胞数は増加したが、sh-Ift88 KN-3細胞ではYAPが核移行する細胞数は増加と減少の二極性を示した。現在は、この詳細なメカニズムを検討中である。

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  • The study of the regulatory mechanisms of cancer bone destruction metabolism and immunity in Hedgehog signaling

    Grant number：18H02999  2018.04 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    SHIMO Tsuyoshi

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    Grant amount：\17160000 （ Direct expense: \13200000 、 Indirect expense：\3960000 ）

    Hedgehog downstream signaling molecules deployed from a comprehensive pathway analysis in the cancer bone destruction microenvironment (Shimo et al. PlosOne 2016) are associated with prognosis in gingival cancer patients with Stage IV jaw bone invasion (Yoshida, Shimo et al. Diagnostics (Basel) 2021).
    In addition, tumor vascular endothelial cells in patients with Stage II introverted tongue cancer showed significantly enhanced expression of Hedgehog signaling and a positive correlation with tumor-associated macrophage (TAM) accumulation (Takabatake, Shimo et al. Int J Mol Sci 2019). We also analyzed the histological and genetical effect of Gli-1 and Gli-2 dual inhibitor on the in vitro study and in vivo cancer bone destruction mouse model.

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  • Analysis of mechanism of regulation of CTGF/CCN2 by RUNX2 in tooth formation

    Grant number：18K09743  2018.04 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    MORITANI NORIFUMI

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    Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）

    Analysis of teeth extract from subjects with cleidocranial dysplasia and normal subjects revealed changes in protein localization of RUNX family transcription factor 2 (RUNX2) and connective tissue growth factor (CTGF/CCN2). Positive correlations were evident between RUNX2 and CTGF/CCN2 gene expression promotion and suppression in Saos-2 cells. Several RUNX2 protein candidate regions were identified that altered CTGF/CCN2 expression in Cos-7 cells. The findings indicate that the structure of RUNX2 protein changes depending on the mutation site of the RUNX2 gene, and that the CTGF/CCN2 expression changes accordingly. These changes result in an altered phenotype of cleidocranial dysplasia involved in tooth eruption.

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  • Novel regulatory mechanism of endochondral ossification via CCN2-VASH1 axis

    Grant number：17H06885  2017.08 - 2019.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Research Activity Start-up

    MURASE Yurika, TAKIGAWA Masaharu, SATO Yasufumi, KUBOTA Satoshi, AOYAMA Eriko, SUZUKI Yasuhiro, HATTORI Takako, YOSHIDA Shoko, SASAKI Akira

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    Grant amount：\2730000 （ Direct expense: \2100000 、 Indirect expense：\630000 ）

    The aim of this study is to investigate a novel regulatory mechanism of endochondral ossification by CCN2 and VASH1. We found that both CCN2 and VASH1 were localized in the hypertrophic chondrocyte layer. CCN2-silencing in chondrocytes reduced the expression of VASH1 and increased apoptotic cells, and its increase was suppressed by a ROS inhibitor, N-acetyl-L-cysteine. These results suggest that up-regulation of CCN2-VASH1 axis may suppress the elevation of ROS level that causes chondrocyte cell death/apoptosis and keep hypertrophic chondrocytes surviving until the terminal stage of chondrogenic differentiation.

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  • New potential of CCN2: Functional evaluation as a Warburg effector

    Grant number：17K19756  2017.06 - 2019.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Exploratory)

    Kubota Satoshi

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    Grant amount：\6370000 （ Direct expense: \4900000 、 Indirect expense：\1470000 ）

    As a result of the investigation with a chondrosarcoma cell line, we found that cellular ATP level was repressed by CCN2 silencing; whereas CCN2 expression was repressed by glycolytic inhibition vice versa. These findings indicate the property of CCN2 as a Warburg booster, which is more than a Warburg effector. Furthermore, through the evaluation of the effects of glycolytic inhibition on the gene expression of all of the CCN family members, we discovered that CCN3 was contrarily induced by glycolytic inhibition. Such CCN3 induction was not observed by the inhibition of aerobic ATP synthesis by mitochondria and thus depends on glycolytic activity in the cells. Collectively, it was clarified in this study that both CCN2 and CCN3 gene expression was under a tight regulation by glycolytic activity, which eventually determines the status of energy metabolism in tumor cells.

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  • Mechanism of onset of osteoarthritis caused by obesity and regulatory effects of CCN2

    Grant number：17K11641  2017.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Nishida Takashi

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    Grant amount：\4680000 （ Direct expense: \3600000 、 Indirect expense：\1080000 ）

    In this study, we showed that angiotensin II (ANG II) suppresses chondrocyte proliferation and differentiation as well as increased CCN2 production in dose-dependent manner. Based on our results using chondrocytes treated with losartan, which is a specific inhibitor of AT1R and those using AT1R-deficient chondrocytes, we clarified that the effects of ANG II are through AT1R. Furthermore, our data indicates that ANG II production is increased by CCN2 deficiency, suggesting that onset of osteoarthritis in Ccn2 deficient mice is involved with increased ANG II.

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  • The investigation of the mechanism of regular arrangement of odontoblasts via extracellular environment sensing sensors

    Grant number：16K11475  2016.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Takaesu Kazumi

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    Grant amount：\4810000 （ Direct expense: \3700000 、 Indirect expense：\1110000 ）

    We studied the mechanism that the inhibition of proliferation by dexamethasone (DEX), which is added to odontoblast differentiation culture medium, is canceled for Intraflagellar transport (Ift) 88 knocked-down pre-odontoblastic KN3 cells (Ift88 is known to function in primary cilia formation and cell cycle control. ). As a result, while involvement of signal pathways via the primary cilia was not recognized, involvement of Ccn4 and Ccn5, which are canonical Wnt signal pathway related genes, was suspected. We then established and analyzed KN3 cells where Ccn4 and Ccn5 were overexpressed. However, it was revealed that Ccn4 and Ccn5 are not involved in the mechanism that cancels the inhibition of odontoblast proliferation by DEX in the Ift88 knocked-down KN3 cells.

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  • Roles of CCN2 and Rab14 in the formation of extracellular matrix

    Grant number：16K11786  2016.04 - 2019.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Hoshijima Mitsuhiro

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    Grant amount：\4810000 （ Direct expense: \3700000 、 Indirect expense：\1110000 ）

    CCN2 and Rab14 strongly expressed in bone, cartilage and lung. To elucidate the roles of CCN2 and Rab14 in osteocyte maturation, we investigated the different expression of osteocyte-related genes between young osteocytes and developmentally mature osteocytes using 3D-cultured MLO-Y4 cells. As the results, in the mature MLO-Y4 cells, rab14, ccn2, col1a1, OCN, c-Fos, Cx43 and Panx3 mRNA expression were significantly increased in comparison with young cells. Furthermore, in the present study, we showed for the first time that intracellular Ca2+ levels were significantly increased in developmentally mature osteocytes in comparison with young osteocytes by flow-induced mechanical stress.
    These findings show that the CCN2 and Rab14 plays an important role in the formation of extracellular matrix, and the intracellular Ca2+ responses in a 3D cellular network in osteocyte.

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  • Mechanism and expression of CD302 as a new regulator of osteoclast maturation

    Grant number：15K11038  2015.04 - 2018.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Aoyama Eriko, HOSHIJIMA Mitsuhiro

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    Grant amount：\4810000 （ Direct expense: \3700000 、 Indirect expense：\1110000 ）

    CD302/DCL-1 is one of the C-type lectin receptors, but the distribution and the function has been mostly not clarified. We found that CD302 was expressed on osteoclasts induced from murine bone marrow cells. The inhibition of CD302 expression caused fragmentation of actin ring in mature osteoclasts and reduced bone resorption in vitro. Also, CD302 was co-localized with CCN2 which is a positive regulator of osteoclast maturation. Moreover, SHP-2 was identified as a potent candidate as a signal transducer of CD302 signaling. These results showed that CD302 could be a new target protein to regulate osteoclast maturation.

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  • Differential analysis and application at the molecular level of the immunosuppressant action base seen from cartilage tissue

    Grant number：15K11248  2015.04 - 2018.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    NAKATA naoki

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    Grant amount：\4810000 （ Direct expense: \3700000 、 Indirect expense：\1110000 ）

    1) We tried to clarify the regulatory mechanism of CCN2 / CTGF gene expression of tacrolimus in vitro using molecular biological methods, but we could not obtain the expected results.
    2) When stimulating HCS-2/8 cells with tacrolimus, analyze exhaustively as well as other variable genes such as dexamethasone, using the microarray method at the time and concentration where CCN2 / CTGF gene expression regulation is the most active Although it was scheduled to do, it could not be achieved due to delay in planning progress.

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  • Analysis of the CTGF/CCN2 expression promotion system which classified cartilage regenerative therapy into the field

    Grant number：15K11247  2015.04 - 2018.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Moritani Norifumi, IIDA Seiji

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    Grant amount：\4810000 （ Direct expense: \3700000 、 Indirect expense：\1110000 ）

    CEBPB, CEBPD-adjusted altered expression of CTGF/CCN2, and their regulatory pathways are suggested to influence IL16 and COL12A1 activities. Interestingly, CEBPB and CEBPD were observed to develop in the nucleus and exhibit expression patterns similar to CTGF/CCN2. Results suggesting CEBPB and CEBPD activity in the CCN2 promoter region were also obtained. Furthermore, results suggesting that CEBPB and CEBPD accelerated proteoglycan synthesis were obtained when they were forcibly expressed. Finally, we also identified a RUNX2 gene frameshift mutation in a cleidocranial dysplasia patient and confirmed RUNX2 expression and CTGF/CCN2 localization using teeth tissue sections.

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  • Study on adhesion system for composite CAD/CAM blocks using molecular control technology

    Grant number：15K11158  2015.04 - 2018.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Nagaoka Noriyuki

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    Grant amount：\4810000 （ Direct expense: \3700000 、 Indirect expense：\1110000 ）

    Since composite CAD / CAM blocks are relatively new materials, laboratory and clinical data are highly needed. Therefore, the structure of composite CAD / CAM blocks was investigated, in particular to assess (1) the effect of sandblasting on their surface topography and (2) the effect of sandblasting and silanization on their bonding receptiveness.
    Sandblasting composite CAD / CAM blocks produced not only an irregular surface but also surface and sub-surface cracks. This was especially so for Shofu Block HC, the surface and sub-surface of which was severely damaged. Hence, composite CAD / CAM blocks should be sandblasted with reduced pressure. Silane treatment after sandblasting improved bond strength.

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  • Effect of CCN2 on the osteocyte function regulating the osteoclast formation, and its possibility as a novel drug of osteoporosis

    Grant number：26462810  2014.04 - 2017.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Nishida Takashi

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    Grant amount：\4940000 （ Direct expense: \3800000 、 Indirect expense：\1140000 ）

    It is well-known that osteocytes play a role in the regulation of bone remodeling. However, the effect of CCN2/CTGF on the bone remodeling in osteocytes is unknown. Therefore, the aim of this study is the investigation of osteoclastogenesis via osteocytes stimulated by CCN2. A mouse osteocytic cell line, MLO-Y4 embedded into collagen gel containing recombinant CCN2 protein, promoted the osteoclast differentiation of RAW264.7 cells inoculated on the collagen gel, and osteocyte-like cells isolated from Ccn2-deficient mice inhibited the differentiation of osteoclasts under the same condition. These findings suggest that osteoclastogenesis is modulated by osteocytes stimulated by CCN2.

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  • Novel function of CCN3: A regulator of endochondral ossification

    Grant number：25462888  2013.04 - 2016.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Hattori Takako, KUBOTA Satoshi, NISHIDA Takashi, TAKIGAWA Masahasu, AOYAMA Eriko

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    Grant amount：\4940000 （ Direct expense: \3800000 、 Indirect expense：\1140000 ）

    To understand a role of CCN3 in bone formation, we generated a transgenic mouse line which is specifically overexpressing CCN3 in cartilage. The mice showed embryonic bone malformations, including shortened long bones, decreased bone mineralization, and delayed appearance of osteoblasts and cells expressing marker genes of late hypertrophy. Blood vessel invasion into the developing cartilage was also inhibited. In contrast, limb mesenchymal cells showed accelerated chondrogenesis. These phenomena correlated with changes in gene expression related to bone and cartilage development. Moreover, we observed degradation of articular chondrocytes and absorption of subchondral bone in adult knee joints. These findings demonstrate a novel role of CCN3 in skeletal development and maintenance of articular cartilage.

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  • Investigation on the biological diarchy by CCN2 and CCN3 for integrated tissue development

    Grant number：25462886  2013.04 - 2016.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Kubota Satoshi, TAKIGAWA Masaharu, HATTORI Takako, NISHIDA Takashi, AOYAMA Eriko

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    Grant amount：\5070000 （ Direct expense: \3900000 、 Indirect expense：\1170000 ）

    Suspecting a biological diarchy by CCN2 and CCN3, CCN3 was overexpressed in fibrogenic cells. Consequently, the gene expression of profibrotic CCN2 and CCN4 were repressed. Also, overexpression of CCN3 disharmonizing the CCN2/CCN3 balance resulted in obvious delay in the final stage of endochondral ossification. New CCN2 molecular counterparts were identified as well.
    Subsequently, in a rat osteoarthritis (OA) rat model, CCN3 that was present in normal articular cartilage was drastically decreased, contrarily to CCN2. Ameliorating effects of CCN3 locally applied to the OA lesion was observed.
    Finally, by analyzing the components of platelets as a model of tissue regenerating tools, inclusion of CCN1, CCN3 and CCN5, as well as CCN2, was clarified therein. A CCN cocktail mimicking platelets showed even greater regeneration potential than CCN2 alone, suggesting its clinical utility.

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  • Analysis of molecular mechanism of muscle heterotopic ossification by forming a network with CCN family proteins

    Grant number：23592732  2011 - 2013

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    NISHIDA Takashi, TAKIGAWA Masaharu, KUBOTA Satoshi, HATTORI Takako, AOYAMA Eriko

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    Grant amount：\5070000 （ Direct expense: \3900000 、 Indirect expense：\1170000 ）

    The protein production of CCN2 (also known as Connective tissue growth factor) was increased in mouse myoblastic cell line C2C12 by treatment with tumor necrosis factor-a, which is produced upon inflammation. CCN2 promoted cell proliferation and the protein production of MyoD in C2C12 cells. Consistent with these findings, in vivo analyses with Ccn2-deficient skeletal muscle showed the decreased PCNA staining and muscle hypoplasia. Furthermore, bone morphogenetic protein (BMP)2-induced Runx2 and Osterix gene expression levels were significantly decreased in C2C12 cells co-treated with CCN2.

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  • Functional analysis of CCN2 as a metabolic supporter and potential clinical applications in chondrocyte regeneration

    Grant number：23592216  2011 - 2013

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    MIYAKE Yoshiaki, AOYAMA Eriko, FURUMATSU Takayuki, KUBOTA Satoshi, OZAKI Toshifumi, TAKIGAWA Masaharu

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    Grant amount：\5330000 （ Direct expense: \4100000 、 Indirect expense：\1230000 ）

    Functional analysis and potential clinical applications of CCN2 as a metabolic supporter in chondrocyte regeneration. The purpose of this study was to analyze the influence of connective tissue growth factor (CCN2) on overall metabolism in chondrocytes, especially energy production and a molecular basis related to the energy production. The result revealed that the absence of CCN2 caused the decrease in the amount of adenosine triphosphate (ATP) in chondrocytes and suppression of glycolysis. Also, CCN2 was shown to be a metabolic supporter in chondrocyte regeneration producing ATP. Furthermore, the effect of articular cartilage regeneration in an osteoarthritis (OA) model suggested future clinical application for osteoarthritis cartilage treatment.

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  • A new protein transport system in cartilage: Multilayered transcytosis

    Grant number：23659872  2011 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    TAKIGAWA Masaharu, KUBOTA Satoshi, HATTORI Takako, NISHIDA Takashi, AOYAMA Eriko

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    Grant amount：\3640000 （ Direct expense: \2800000 、 Indirect expense：\840000 ）

    Protein transportation in cartilage has been believed to be due to diffusion because there is no blood vessel in cartilage. In the present study, we revealed that low-density lipoprotein receptor-related protein-1(LRP-1) transports connective tissue growth factor/CCN family 2 (CTGF/CCN2/CCN2)in cartilage by transcytosis, indicating that this mechanism is a new protein transport system in cartilage. We also uncovered that cartilage-specific defect of LRP-1 resulted in skeletal disorders.

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  • The technological development of bioengineered regenerated tooth, based on the mechanism of development

    Grant number：22249064  2010.04 - 2014.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    KUBOKI Takuo, TAKIGAWA Masaharu, SONOYAMA Wataru, TSUJI Takashi, ASAHARA Hiroshi

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    Grant amount：\46670000 （ Direct expense: \35900000 、 Indirect expense：\10770000 ）

    In the dental field, the regeneration of complete tooth is ultimate goal. First, we examined whether fully functional bioengineered tooth could regenerate utilizing an organ germ method with the permanent tooth bud tissue of the post-natal canine, we succeeded in it, for the first time in the world. Next, in order to understand the mechanism of tooth development, we performed the screening and clarified that several Hox gene specifically expressed in the development of tooth.

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  • The analysis of binding of CTGF/CCN2 to RANK and its effects on RANK/RANKL signaling

    Grant number：22791788  2010 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    AOYAMA Eriko, TAKIGAWA Masaharu, KUBOTA Satoshi, NISHIDA Takashi

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    Grant amount：\4030000 （ Direct expense: \3100000 、 Indirect expense：\930000 ）

    CCN2/CTGF which is a member of CCN2 family proteins binds to various cytokines and modulates the effects. We screened the binding proteins to CCN2/CTGF and found receptor activator of NF-kappaB(RANK). CCN2/CTGF also could bind to OPG which was a decoy receptor and inhibited the effect of RANK. In the RAW264. 7, preosteoclast, CCN2/CTGF augmented the stimulation of RANKL(RANK ligand) and attenuated the inhibitory effect of OPG on RANK/RANKL signaling. These data showed that CCN2/CTGF enhanced differentiation of osteoclast via two different pathways.

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  • Development and medical application of peptide and RNA aptamers that bind to CCN2

    Grant number：21592360  2009 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    KUBOTA Satoshi, TAKIGAWA Masaharu, HATTORI Takako, NISHIDA Takashi, AOYAMA Eriko

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

    CCN2 is known to promote harmonized regeneration of bone and cartilage tissues and to be involved in fibrotic disorders of a variety of organs. Therefore, regulating CCN2 function is of great significance in the field of regenerative medicine and fibrosis therapeutics. In this study, we designed, synthesized and evaluated the effect of aptamers that bind to CCN2, in order to control the molecular action of CCN2. As a result, we could obtain a few aptamers that could promote cartilage regeneration, or might regulate bone remodeling.

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  • Role of a ubiquitin ligase for Sox9 on endochondral ossification and neurological disorder

    Grant number：21592359  2009 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    HATTORI Takako, TAKIGAWA Masaharu, KUBOTA Satoshi, NISHIDA Takashi, AOYAMA Eriko

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

    Sox9 is a master regulatory transcription factor of the SRY gene family regulating chondrogenesis as well as neural development. In this report, we identified a ubiquitin ligase which binds specifically and regulates cellular concentration of Sox9, and examined the role of the ubuquitin ligase on endochondral ossification as well as neurological disorder through controlling cellular concentration of Sox9.

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  • Clarification of molecular mechanism on the osteoclastogenesis promoted by CCN family 2/connective tissue growth factor

    Grant number：20592173  2008 - 2010

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    NISHIDA Takashi, TAKIGAWA Masaharu, KUBOTA Satoshi, HATTORI Takako

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    Grant amount：\4030000 （ Direct expense: \3100000 、 Indirect expense：\930000 ）

    Combination of RANKL, M-CSF and CCN2 significantly enhanced tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell formation compared with RANKL and M-CSF. Therefore, we suspected the involvement of CCN2 in cell-cell fusion during osteoclastogenesis. To clarify the mechanism, we isolated fetal liver cells from Ccn2-null mice at E14.5 days, and investigated TRAP-positive multinucleated cell formation. The results showed that RANKL-induced osteoclastogenesis was impaired in fetal liver cells from Ccn2-null mice, and the impaired osteoclast formation was rescued by the addition of exogenous CCN2. These results suggest that CCN2 involves in cell-cell fusion during osteoclastogenesis.

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  • Regulation of CCN family gene expression via micro RNA regulatory network and its Biological signficance

    Grant number：19592142  2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    KUBOTA Satoshi, TAKIGAWA Masaharu, HATTORI Takako, NISHIDA Takashi

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

    マイクロRNA(miRNA)は小分子noncoding RNA(ncRNA)であり、個々のmiRNAが数千のmRNAの3'非翻訳領域を標的として、遺伝子の発現をネットワーク的に制御する。本研究ではCCNファミリー遺伝子の代表的メンバーであり、間葉系組織の成長ならびに再生を指揮するCCN2遺伝子が特定のmiRNAの制御ネットワーク下にあることを実証した。さらに、このmiRNAによる制御が、軟骨細胞の成熟形質の獲得・維持に重要であることも明らかとなった。またmiRNAの作用機構や軟骨細胞後期分化における役割を今後解明していく上で、有用な知見をも得ることができた。

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  • 付着歯肉の分化に関連した特異的遺伝子・蛋白の同定とその機能解析

    Grant number：19659507  2007 - 2008

    日本学術振興会  科学研究費助成事業  萌芽研究

    窪木 拓男, 高柴 正悟, 園山 亘, 滝川 正春

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    Grant amount：\3200000 （ Direct expense: \3200000 ）

    1.付着歯肉組織と遊離歯肉組織の遺伝子発現解析
    前年度のマウスならびにラット歯肉組織の組織学的検討をもとにして,成体マウスの口腔内から実態顕微鏡下で付着歯肉と遊離歯肉をそれぞれ採取した、この組織からmRNAを抽出し,cDNAマイクロアレイを行い,両者の遺伝子発現を比較・検討した.
    その結果,付着歯肉で発現量の高い遺伝子として,mmp12, integrin(alpha6), laminin(beta3), HIF-1a, VEGF, tenomodulin, collagen(typeV, alpha2), integrin(beta4)などが抽出された.一方,遊離歯肉で発現量の高い遺伝子としてIGFBP2, RABL3(member of RAS oncogene family-like3), RASA3(RAS p21 protein activator3), elastinなどが抽出された.既知の発現パターンと機能から考察するといくつかの遺伝子はたいへん興味深い研究対象と考えられた.
    2,ヒト歯肉上皮細胞の培養
    倫理委員会の許可を得て,抜歯時に得られたヒト歯肉サンプルから歯肉上皮細胞を分離し,同時に得た歯原性上皮細胞とその差異を比較,検討した.
    その結果,歯肉上皮細胞は培養条件下では寿命が短く,cumulative population doubling(cPD)は平均8であった。一方,歯原性上皮細胞は平均16のcPDを示した.また,両者ともに上皮細胞のマーカーであるサイトケラチン14とE-cadherinを遺伝子レベルで発現していたが,amelogeninの発現は歯肉上皮細胞では認めなかった.すなわち,歯肉上皮細胞は歯原性上皮細胞と比較して,明らかに異なるフェノタイプを有していることを明らかにした.

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  • MMPの新機能:マトリクス合成促進因子の転写因子としての役割

    Grant number：19659487  2007 - 2008

    日本学術振興会  科学研究費助成事業  萌芽研究

    滝川 正春, 久保田 聡, 服部 高子, 西田 崇, 青山 絵理子

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    Grant amount：\3300000 （ Direct expense: \3300000 ）

    (1)MMP-3と複合体を形成する転写関連因子の探索と機能解析;MMP-3とnuclear MMP-3associated protein (NuMAP)の発生、内軟骨性骨化過程における遺伝子発現変動の解析:まず、マウスの発生段階でのこれら遺伝子の発現変動をin silicoでESTデータベースを活用し解析した結果、MMP-3の制御標的であるCCN2遺伝子発現は原腸陥入以後成体に至るまでは誘導されること、またMMP-3は出生時以後に発現が誘導されることが明らかになった。これに対してNuMAPであるretinoblastoma binding protein4(RBBP4)、nuclear receptor co-repressor1(NRCR1)、Interleukin enhancer binding factor2(ILF2)は卵細胞から成体に至るまで広い発生段階で遺伝子発現がみられた。続いてマウス成長軟骨初代培養細胞増殖・分化系でRBBP4とILF2遺伝子発現が、共に、後期分化、つまり肥大化に向かうに従って上昇することをリアルタイムRT-PCRで明らかにした。以上より、NuMAPのうちRBBP4およびILF2は、発生毅階で見る限りではcofactorとは考えにくいものの、内軟骨性骨形成においてはMMP-3によるCCN2遺伝子の転写活性化を支える役割を果たすものと考えられる。
    (2)他のMMPsによるCCN2/CTGF遺伝子の転写制御の検討:軟骨細胞様HCS-2/8細胞におけるCCN2遺伝子プロモーター活性を、MMP-2/9特異的阻害剤の存在下で評価した結果、MMP-3特異的阻害剤でみられた用量依存的な転写活性抑制効果はみられなかった。したがってMMP-2およびMMP-9はMMP-3とは異なり、MMPとしての古典的機能と関連した形では、CCN2遺伝子の転写制御にかかわっていないことが示唆された。

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  • Analysis of the role of cartilage-specific gene in endochondral bone formation using BAC (bacterial artificial chromosome)-transgenic mice

    Grant number：19592145  2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    HATTORI Takako, TAKIGAWA Masaharu, KUBOTA Satoshi, NISHIDA Takashi, AOYAMA Eriko

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    Grant amount：\4680000 （ Direct expense: \3600000 、 Indirect expense：\1080000 ）

    全長10型コラーゲン遺伝子を含むbacterial artificial chromosome(BAC)DNAの10型コラーゲンプロモーター領域下流にSox9 cDNAを挿入し、Sox9を肥大化軟骨層に異所性に過剰発現するBACトランスジェニックマウスを作製し,(1) 骨髄の消失、肥大化軟骨層への血管侵入の遅延、肥大化軟骨細胞層の延長に起因する骨の短縮、(2) 延長した肥大化軟骨細胞層でのSox9の強い発現に加え、肥大化軟骨マーカー遺伝子の発現の低下、(3) Sox9は直接的にyθgfプロモーター活性を低下させる事、を明らかにし、これらの事からSox9の肥大軟骨細胞層における消失は、血管の侵入、骨髄の形成を可能にし,正常な内軟骨性骨形成に必須である事をin vivoおよびin vivoで明らかにした。

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  • 結合組織成長因子(CCN2/CTGF)を用いた顎顔面領域の三次元軟骨再生

    Grant number：18592121  2006 - 2007

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    藤澤 拓生, 服部 高子, 滝川 正春, 窪木 拓男, 上原 淳二

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    Grant amount：\3950000 （ Direct expense: \3500000 、 Indirect expense：\450000 ）

    本研究では,ドナーサイトから採取した自己軟骨細胞をCCN2/CTGFとともに培養・増幅し、付形した3次元スキャフォードに播種後に移植する新しい顎顔面再生療法を開発するための基礎研究を行い,以下の知見を得た.
    細胞実験にはすべて4周齢の日本白色ウサギの耳介より採取した初代耳介軟骨細胞を用いた.
    1.CTGFの細胞増殖に対する効果をMTS assayで評価したところ,50ng/mlのCTGF添加により耳介軟骨細胞の細胞増殖は,細胞播種後5日目と7日目にコントロール群と比較すると有意に促進された.
    2.DNA合成に対するCTGFの効果を[^3H]thymidineの取り込みを指標に検討したところ,CTGFは濃度依存性に耳介軟骨細胞のDNA合成を上昇させ,50ng/mlでピークに達した(コントロールの約1.5倍).
    3.プロテオグリカン合成に対するCTGFの効果は[^<35>S]sulfateの細胞内への取り込みを指標に検討した.プロテオグリカン合成もDNA合成と同様に添加したCTGFの濃度依存性に上昇し,50ng/mlでピークに達した(コントロール群の約1.4倍).
    4.軟骨細胞の分化関連マーカー遺伝子の遺伝子発現に対する効果はリアルタイムPCRにて検討した.50ng/mlのCTGFでコンフルエントに達した耳介軟骨細胞を48時間刺激することにより,CTGFの遺伝子発現は1.9倍,エラスチンの遺伝子発現は5倍,2型コラーゲンの遺伝子発現は1.5倍上昇したが,10型コラーゲンの遺伝子発現には有意な発現上昇は認められなかった.またエラスチンのタンパク産生をビクトリアブルー染色で確認したところ,CTGF添加によりビクトリアブルーの染色性は亢進していた.すなわち,エラスチンのタンパク産生はCTGF添加によりコントロール群と比べると亢進していた.一方,アリザリンレッド染色ではその染色性にコントロール群との差は認められなかった.すなわち,CTGF添加により耳介軟骨細胞の石灰化は誘導されなかった.
    5.In vivoにおける軟骨再生に対するCTGFの効果は,細胞ペレットをヌードマウスの背部皮下に移植することで検討した.移植後4週に移植片を取り出したところ,CTGF処理群はコントロール群と比べると移植片の大きさが明らかに大きくなっていた.移植片をサフラニン染色したところ,CTGF群,コントロール群ともにサフラニン染色陽性であったが,CTGF群のほうがその染色性は亢進していた.
    これらの結果から,CTGFには耳介軟骨細胞においてそのphenotypeを増強する働きがあると考えら,CTGFを弾性軟骨の修復・再生にも応用できる可能性が示唆された。

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  • Establishment of Information Basis for Tooth Regeneration

    Grant number：17209062  2005 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    KUBOKI Takuo, UEDA Minoru, KANYAMA Manabu, TAKASHIBA Syogo, TSUJI Takashi, TAKIGAWA Masaharu, ASAHAR Hiroshi, TUCHIMOTO Youhei, SONOYAMA Wataru, TAGAWA Youichi

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    Grant amount：\48880000 （ Direct expense: \37600000 、 Indirect expense：\11280000 ）

    マウスの歯の発生時に認められる遺伝子を検索し、従来報告のなかった28個の遺伝子を同定した。エナメル質形成細胞の成熟は、周囲に存在する細胞が制御していることを証明した。高脂血症治療薬(スタチン)は、象牙質の形成を促進し、歯科治療薬として応用しうることを示した。顎骨に存在する細胞は、手足の骨の細胞とは異なる性質を有していること、また、顎骨の再生促進に成長因子(結合組織成長因子、塩基性線維芽細胞増殖因子)が応用可能であることを確認した。

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  • Role of CCN2 as a trans-modulator in the integrated development of bone, cartilage and hematopoietic systems

    Grant number：17591938  2005 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    KUBOTA Satoshi, TAKIGAWA Masaharu, HATTORI Takako, NISHIDA Takashi, AOYAMA Eriko

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    Grant amount：\3500000 （ Direct expense: \3500000 ）

    1. Investigation on the production and distribution of CCN2 in hematopoietic cells in bone marrow
    Identification of CCN2 producers and target cells : Based on the fact that platelets harbor a vast amount of CCN2, we hypothesized megakaryocytes as the major CCN2 producer. Initially, we evaluated the CCN2 mRNA expression and protein production by a megakaryocytic CMK cell line, but failed to detect them. Next, we isolated human hematopoietic stem cells and drove them differentiate into megakaryocytes in vitro. As a result, we could detect ccn2 mRNA at the final stage of the differentiation of megakaryocytes in vitro. In addition, by analyzing bone marrow histochemically, a putative CCN2-associated cell surface receptor, EphA4, was detected on megakaryocytes, which may contribute to the uptake of CCN2 from outside upon the formation of platelets.
    Evaluation of the effects of CCN2 on hematopoietic cells : We showed that mesenchymal knocking-down of ccn2 expression resulted in the repression of osteoclast development from the macrophage-monocyte lineage. This finding strongly indicates that osteoclast progenitor is one of the CCN2 target cells.
    2. Analysis of the interaction between CCN2 and other cytokines in bone marrow.
    First of all, we for the first time clarified that CCN2 provoked the gene expression of M-CSF, which is critically required for the differentiation of the cells in the monocyte lineage, in chondrocytes. Subsequently, by using a bacteriophage-display system, we screened dodecapeptides that specifically interacted with each module of tetramodular CCN2 molecule. With the data obtained, common peptide binding motifs were extracted in silico. We synthesized a peptide with one such motif and found that it actually repressed the effects of CCN2 on chondrocytes in vitro.

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  • Establishment of an autologous cell transplantion method using mesenchymal stem cells for alveolus bone regeneration.

    Grant number：16591947  2004 - 2005

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    FUJISAWA Takuo, KUBOKI Takuo, TAKIGAWA Masaharu, UEHARA Junji

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    Grant amount：\3100000 （ Direct expense: \3100000 ）

    The purposes of this research are to investigate the possibility of autologous mesenchymal stem cell transplantion method for alveolus bone regeneration using connective tissue growth factor (CTGF).
    1. Isolation of human bone marrow cells and cell characterization.
    Bone marrow cells were isolated from human iliac bone marrow of volunteer. Human bone marrow cells were plated and cultured in DMEM containing 10% FBS. Moreover, STRO-1 expressing cells were identified by immunostaining from culture of passage 9 cells, and these cells showed the multilineage differentiation (osteoblastic and adipogenic).
    2. Effects of CTGF on stem cells behavior.
    1) Cell attachment efficiency onto hydroxyapatite disks is enhanced by coating CCN2/CTGF dose-dependently, and CCN2/CTGF activated p38 MAPK signal pathway via αvβ3 integrin.
    2) CCN2/CTGF significantly increased the cell proliferation dose dependently.
    3) The migration assay using Chemotaxicell indicated that CCN2/CTGF significantly increased the cell migration.
    4) CCN2/CTGF did not affect cell differentiation to the osteoblast.
    5) CCN2/CTGF also enhanced the endothelial cell attachment and proliferation.
    6) In vivo implantation study indicated that CCN2/CTGF enhance the stem cell survival and induce their migration into the porous hydroxyapatite scaffold.

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  • RNA干渉を用いたCCN遺伝子ファミリーの包括的機能解析とその応用

    Grant number：16659511  2004 - 2005

    日本学術振興会  科学研究費助成事業  萌芽研究

    滝川 正春, 久保田 聡, 服部 高子, 椋代 義樹

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    Grant amount：\3200000 （ Direct expense: \3200000 ）

    ・マウス15日胚の頸骨成長板軟骨におけるCCNファミリータンパク質の局在を免疫染色で調べたところ、成長板に6つのメンバーすべての分布がみられた。しかし、その分布には差異があり、CCN2/CTGFとCCN5は肥大軟骨細胞層全域で強染し、CCN1/Cyr61とCCN4/WISP1は前肥大化軟骨細胞層で強染し石灰化層では染色性が減弱した。一方、CCN3と6は前肥大化軟骨細胞層で強染し、肥大軟骨細胞層で一旦染色性が減弱したのち再び石灰化層で染色性が増強した。
    ・ヒト軟骨細胞様細胞株HCS2/8で、CCNファミリーのmRNAレベルをRT-PCRで調べたところ、すべてのメンバーが定量可能なレベルで発現していた。特に、CCN2が顕著に高く、続いてCCN1とCCN6が高発現していた。
    ・マウス軟骨細胞、骨芽細胞および線維芽細胞の3種の細胞でCCNファミリーの発現を比較したところ、CCN2は軟骨細胞にほぼ特異的に、CCN4と6は軟骨細胞と骨芽細胞とで強く発現しており、CCN4は線維芽細胞で強い発現が見られた。CCN1およびCCN5の発現は3種の細胞間で大差は無かった。
    ・軟骨培養細胞において、軟骨分化を促進させるデキサメサゾンにより、CCN2のみならずCCN1,4および5の発現も転写段階で亢進することを見出した。
    ・CCN2のノックアウトマウスから初代軟骨細胞を分離培養し、他のCCNファミリーメンバーの発現を調べたところ、CCN3は著明に上昇し、CCN6は著明に低下していた。また、線維芽細胞の場合ではCCN1,3,4および6で著明な低下が見られた。即ち、これらのCCNメンバーの発現がCCN2により調節されていること、またその調節機構には組織特異性が見られることが明らかになった。

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  • Cloning, Expression and Identification of Specific Genes related Osseointegration to Titanium.

    Grant number：15390592  2003 - 2005

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    KANYAMA Manabu, KUBOKI Takuo, TAKIGAWA Masaharu, ARAKAWA Hikaru, SUZUKI Kouji, FUJISAWA Takuo

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    Grant amount：\14800000 （ Direct expense: \14800000 ）

    The aim of this study is to clarify the cell behavior induced by titanium and to isolate specific genes that promote the titanium implant-bone integration. Especially, to identify the master key genes related osseointegration to titanium, the osteoblastic cell line, MC3T3-E1 cells were cultured on titanium coated glasses and the gene expression were analyzed.
    1)Titanium and chrome coated glasses
    Ti and Cr were coated to polished glass surfaces (33 mm in diameter by 1.5 mm in thickness) in a high vacuum condition. Ti and Cr coated glass disks were placed in a 6 well plate and fixed by silicone rings. Non-coated glass disks were served as controls.
    2)Cell attachment, proliferation and differentiation assessments.
    Initial cell attachment and proliferation of MC3T3-E1 cells were estimated by MTS-assay (CellTiter 96【○!R】 AQueous One Solution, Promega, USA), and cell differentiation was evaluated by alkaline phosphatase activity assay. The mean relative amount of the attached cells on the Ti-coated glass was significantly higher than those on non-coated and Cr-coated glass at 3 hours after seeding. On the same way the mean cell number on Ti-coated glass at 3 days after seeding was significantly higher than those of other conditions. The mean alkaline phosphatase(ALP) activity of the seeded osteoblasts also increased with time in these three conditions, while the ALP activity level on the Ti-coated glass at 14 days after seeding was significantly higher than those of other conditions. These results suggest that, Ti-coated glass plate accelerated the cell attachment, proliferation and differentiation of the MC3T3-E1 cells, compared to the non- and Cr-coated glass plates
    3)Effect of gene expression of osteoblast on titanium
    Osteoblasts were cultured on Ti coated, Cr coated and non-coated glass plates. And then differentially expressed genes were identified by cDNA subtractive hybridization. Twenty independent clones were isolated and by nucleotide sequencing of these clones, seven clones were identified including EST genes ; xab-2,sod-1,galectin-1,actin related protein 2/3 mRNA, RIKEN cDNA 2210013021 gene, EST 601086505F1, and EST 01439. And galectin-1,xab-2,sod-1 gene expression on Ti-coated glass were higher than non-coated, Cr-coated glass.
    These results suggest that Ti-coating is more advantageous for osteoblastic cell attachment, proliferation and differentiation than Cr or non-coating and galectin-1,xab-2 and sod-1 up-regulation could be related to the Ti-bone integration.

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  • 間葉系幹細胞の遺伝子発現プロファイル解析と硬組織再生への応用

    Grant number：15659443  2003 - 2004

    日本学術振興会  科学研究費助成事業  萌芽研究

    大山 和美, 中西 徹, 田中 紀章, 滝川 正春, 久保田 聡, 大山 和美

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    Grant amount：\3300000 （ Direct expense: \3300000 ）

    (1)前年度までの研究でヒトテロメラーゼ遺伝子(hTERT)による不死化間葉系幹細胞クローンを数多く樹立,解析してきたが,その中で唯一クローン12が骨軟骨へと分化し得た.そこで本年度はエピジェネティックな解析を含め,さらなる解析を本クローンに絞って行った.
    (2)hTERTを用いた上記のin vitroの検討結果を援用しin vivoで骨髄から幹細胞を引き出して組織再生を行う方法を検討した.クローン12では血管内皮細胞増殖因子(VEGF)などの多くの増殖因子遺伝子の発現がみられたので,まずは多くの増殖因子と相互作用をもち,間葉系組織の成長分化を幅広く促進する結合組織成長因子(CTGF)を試用した.すなわちこれを徐放性担体に適用し,ラット膝関節に作成した軟骨全層欠損に封入した.全層欠損を作成したのは組織再生を間葉系幹細胞に期待したからである.その結果CTGFを封入した場合ほぼ完全な軟骨組織の再生が観察された.これに対し対照群では全く軟骨組織が形成されなかった.
    (3)2の結果から間葉系幹細胞の軟骨再生能力が示唆されたが,これをさらに検証するためマウス骨髄幹細胞を採取し,それがCTGFのもと硬組織再生を行いうるかをin vitroで検討した.マウス骨髄幹細胞を長期に維持し,CTGF存在下・非存在下で軟骨細胞分化初期マーカーであるsox9遺伝子および骨芽細胞分化マーカーであるcbfa1/runx2の発現を定量した.その結果CTGF存在下で骨髄幹細胞は軟骨細胞に分化するに並行して,骨芽細胞へも分化しうることも明らかとなった.以上に関連して,cbfa1ノックアウトマウス胎児におけるctgfの発現パターンを解析したところ,本来発現のみられる歯牙形成や骨化に向かう部分にctgfの発現は見られなかった.以上の結果は,幹細胞からの硬組織再生における両遺伝子の協調的役割を示すものである.

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  • 口腔インプラントの骨結合獲得難易度を予測する生物学的診断法の開発

    Grant number：15659463  2003 - 2004

    日本学術振興会  科学研究費助成事業  萌芽研究

    窪木 拓男, 高柴 正悟, 滝川 正春, 荒川 光, 藤沢 拓生

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    Grant amount：\3300000 （ Direct expense: \3300000 ）

    1.チタンの細胞培養および遺伝子発現への影響
    骨芽細胞様細胞株(MC3T3-E1細胞)の細胞培養培養および遺伝子発現に対するチタンの影響を検討した。
    1)チタンプレート
    ポリスチレン製の培養皿と表面粗さを同程度にするために,研磨ガラスにチタンを真空蒸着したものを使用した。
    2)細胞接着への影響
    通常の培養皿と比較してチタンは細胞接着を抑制する傾向にあった。
    3)細胞増殖への影響
    通常の培養皿と比較して,細胞播種後1,2日ではチタンでは増殖が抑制されるものの3日では両材料ともコンフルエントに達した。
    4)細胞分化への影響
    骨芽細胞の分化の指標のひとつであるアルカリホスファターゼ活性は,両材料ともに細胞がコンフルエントになった後5日目ごろより上昇し,14日目でピークを向え,21日目では低下した。チタンでは通常の培養皿と比べてアルカリホスファターゼ活性は抑制された。
    5)遺伝子発現への影響
    通常の培養皿と比較し,チタンの遺伝子発現への影響をサブトラクティブハイブリダイゼーション法にて検討したところ,両材料間で発現に差のあるsod-1,xab-2の遺伝子を検出した。
    6)リアルタイムPCR法による遺伝子発現の変動
    サブトラクティブハイブリダイゼーション法にて検出した発現に差のあるsod-1,xab-2の経時的な発現の変動を検討したところ,培養皿では細胞播種後5日目で発現のピークを向え,その後低下した。チタンでは発現のピークが10日目前後と培養皿より遅延し,発現も抑制されていた。

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  • Study of a key factor in chondrogenic differentiation for craniofacial skeletal regeneration

    Grant number：14207092  2002 - 2004

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    YANMAMOTO Teruko, TAKIGAWA Masaharu, YAMASHIRO Takashi, KURODA Shingo, FUKUNAGA Tomohiro

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    Grant amount：\49660000 （ Direct expense: \38200000 、 Indirect expense：\11460000 ）

    The purpose of the present study was to investigate a key factor in chondrogenic differentiation that play a role in craniofacial skeletal development.
    1.We evaluated the expression of CTGF, type I, type II, and type X collagen in chondrocytes of different types of cartilages, including mandibular condylar cartilage, cartilage formed during the healing of mandibular ramus factures, femoral growth plate cartilage, and femoral articular cartilage revealed by in situ hybridization. Among these different types of cartilages we found distinct patterns of CTGF expression. Growth plate cartilage showed localization of CTGF in the hypertrophic chondrocytes that expressed type X collagen with less expression in proliferating chondrocytes that expressed type II collagen, whereas it was also expressed in the proliferating chondrocytes that expressed type I collagen in the condylar cartilage, the articular cartilage, and the cartilage appearing during fracture healing. In contrast, the growth plate cartilage were negative for type I collagen and showed sparse expression of CTGF in the proliferating chondrocytes. The spatial distribution of CTGF in the cartilages with type I collagen suggested its role in the early differentiation of those cartilages.
    2.Runx1,Runx2, and Sox9 expression was evaluated by in situ hybridization in the growing craniofacial bones of embryonic day (E)12-16 mice. In addition, we evaluated Runx2 expression in the growing face of Runxl knockout mice at E12.5 and Runx1 expression in Runx2 knockout mice at E14.5. Runx1 and Sox9 were expressed in cartilage, and the regions of expression expanded to the neighboring Runx2-expressing osteogenic regions. Expression of both Runx1 and Sox9 was markedly downregulated on ossification. Runx1 and Sox9 expression was absent in actively modeling or remodeling bone tissues in ossified craniofacial bones. Runx2 expression was not affected by gene disruption of Runx1, whereas the expression domains of Runx1 were extended in Runx2^<-/-> mice compared with wildtype mice. These results suggest that Runx1 may play a role in incipient intramembranous bone formation.
    3.We investigated that the function of Zac1 in endochondral bone formation. Chondrocytes were isolated from the 17-day embryonic chick sterna. RT-PCR analysis revealed that Zac1 expression was decreased during 3-week culture. To examine the effect of Zac1 on chondrocyte differentiation, we characterized chondrocytes transfected Zac1 gene by chick retrovirus compared to mock transfected group. After retinoic acid(RA) treatment, type IX collagen expression was decreased, and MMP-13 and ADAM-TS5 expression were increased in mock transfected group. In contrast, these changes in Zac1-infected chondrocytes treated with RA were markedly inhibited. These results suggest that Zac1 may play a role in the metabolism of the cartilage.
    4.Normal newborn mice mandibular condylar chondrocytes from type I collagen-expressing cells and non-type I collagen-expressing cells were isolated by laser capture microdissection(LCM) and then subjected to microarray analysis. LCM allows isolation of chondrocytes from individual zones of mandibular condylar cartilage for comparative analysis. These techniques will hopefully serve as a guide for the further analysis.

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  • Establishment of a autologous cell transplantion method using mesenchymal stem cells for perio-dontal tissue and alveolus bone regeneration.

    Grant number：14370632  2002 - 2004

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    KUBOKI Takuo, UEDA Minoru, TAKIGAWA Masaharu, TAKASHIBA Shogo, MAEKAWA Kenji, YOSHIDA Yasuhiro

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    Grant amount：\14800000 （ Direct expense: \14800000 ）

    1.Isolation human bone marrow cells and cell culture.
    Bone marrow cells were isolated from human iliac bone marrow of volunteer. Human bone marrow cells were plated and cultured in DMEM containing 10% FBS. Culture medium was changed every 3 days, and their multipotent (osteoblastic and adipogenic) differentation abilities were confirmed
    2.Connective tissue growth factor (CTGF/CCN2) enhanced hMSC attachment, migration and survival in a hydroxyapatite scaffold
    Human bone marrow cells were incubated to attach onto porous HA blocks for a week. The porous HA/cells hybrids were implanted subcutaneously in nude mice (4 week-old) with CTGF (1ug) or distilled water (control).
    The implants were harvested after 4 weeks for SEM observation. SEM observation supported that hBMSC-like cells migrated and survived inside of the porous HA scaffold with CTGF application, while without CTGF, no viable cells were observed inside of the scaffold.
    3.hMSC initial attachment and proliferation enhanced on titanium
    Adsorption of poly phosphoric acid to Ti disk surface was achieved by immersing Ti disk poly phosphoric acid solution (1 wt%) for 24 hours. Adsorption of polyphosphoric acid onto Ti disks enhanced attachment and proliferation of hMSC.
    4.Effect of gene expression of osteoblast on titanium
    Osteoblast was cultured on titanium dish and searched a titanium specific gene by cDNA subtractive hybridization. It became clear on titanium that sod-1, gene expression of ribosomal protein L19 were restrained significantly.

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  • Functional dissection and medical application of the 4 modules in the chondrocyte-derived growth factor, ecogenin/CTGF.

    Grant number：14571762  2002 - 2003

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    KUBOTA Satoshi, NISHIDA Takashi, NAKANISHI Tohru, TAKIGAWA Masaharu, MUKUDAI Yoshiki

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    Grant amount：\3500000 （ Direct expense: \3500000 ）

    1. Establishment of the production and detection system with specific antibodies of each module of ecogenin/CTGF : Firstly, each module was independently prepared by a Brevibacillus production s stem, and the epitopes of anti-CTGF antibodies were located. As a result at least one antibody against each module, IGFBP, VWC, TSP1 or CT, was obtained Among the ELISA systems we established, the most sensitive one is already in use for subsequent research. Additionally, the other ELISA systems to quantify CTGF subfragments were also established.
    2. Investigation of the roles of modular structure in cell growth and differentiation : Utilizing each purified module, we examined if the signal transduction cascades in chondrocytic HCS-2/8 cells were activated. As a result, a few different pathways were activated by specific modules. Since different results were obtained with other cell types, CTGF is supposed to use multiple signaling pathways differentially. Of note, proteoglycan synthesis by HCS-2/8 was rather enhanced by a few module-specific antibodies, whereas proliferation was inhibited by those antibodies. These findings suggest the utility of the antibodies in therapeutics as well as the CTGF derivatives. Next, we evaluated the effects of the modules on cell adhesion and found the promoting effects of all of the modules. Among the four, CT was the most effective. Finally, effects of overexpression of the modules on cell cycle was evaluated. Then, dimodular TSP-CT and single CT were suggested to arrest the cell cycle at M-phase. As such, particular care should be taken for CT module in considering therapeutic application.
    3. Experimental therapeutics with animal models : Prior to the application of modular mutants, wild type CTGF was applied to the experimental rat cartilage defect models and the effects were evaluated. Then CTGF was found to regenerate damaged articular cartilage. This methodology is going to be applied to the evaluation of modular mutants.

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  • Development of the methods for application of the factors that biologically accelerate reparative dentin formation

    Grant number：14571844  2002 - 2003

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    SONOYAMA Wataru, TAKIGAWA Masaharu, TAKASHIBA Shougo, KUBOKI Takuo

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    Grant amount：\3900000 （ Direct expense: \3900000 ）

    1. Pulp cell isolation from human extracted tooth and confirmation of their phenotype
    Under permission of ethical committee, pulp cells were isolated from human extracted tooth. RT-PCR was carried our to confirm their gene expression profile and phenotype. As a result, they expressed odont oblast-specific gene, dentin sialophosphoprotein (DSPP), and were suspected to be odont oblast lineage.
    2. Effects of Growth factors on their attachment, proliferation, and differentiation
    Effects of growth factors, e.g., transforming growth factor-beta1 (TGF-beta1), basic fibroblast growth factor (bFGF), and connective tissue growth factor (CTGF), on their attachment to plastic dish were investigated. As a result, adsorption of these growth factors enhanced their attachment to plastic dish. Effects on their proliferation and alkaline phosphatase (ALPase) activity were also investigated. Concerning about proliferation, only TGF-beta1 enhanced their proliferation. While ALPase activity was downregulated by TGF-beta1 and bFGF.
    3. Effects of hydroxyapatite (HAP) on their attachment
    To estimate compatibility of HAP with pulp-derived cells, their attachment onto HAP was investigated. As a result, attachment onto HAP was significantly higher compared to plastic dish made of polystyrene. Adsorption of growth factors onto HAP tended to enhance attachment, but the difference was not significant.
    4. Effect of HAP on their gene expression
    To estimate that HAP have an effects on gene expression of pulp-derived cells or not, they were seeded onto HAP and their gene expression were investigated by RT-PCR. As a result, DSPP and type 1 collagen gene expression were significantly enhanced.

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  • Molecular mechanism of temporomandibular joint osteoarthritis and gene therapy for degraded, cartilage

    Grant number：14571843  2002 - 2003

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    FUJISAWA Takuo, TAKIGAWA Masaharu, NISHIDA Takashi, KUBOKI Takuo, MAEKAWA Kenji

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    Grant amount：\4000000 （ Direct expense: \4000000 ）

    The purposes of this research are to clarify the mechanism of cartilage degradation in osteoarthritis (OA) and to investigate the possibility of gene therapy for articular cartlige restoration using connective tissue growth factor (CTGF).
    First, we investigated the effects of CTGF/Hcs24 transduced by recombinant adenoviruses on the rabbit articular cartilage (RAC) cells in vitro. When RAC cells were infected with adenoviruses containing the CTGF/Hcs24 gene, RAC cells expressed CTGF/Hcs24 mRNA and produced CTGF/Hcs24 protein. RAC cells synthesized more proteoglycan than the control cells. These results suggest that CTGF is useful factor for cartilage repair.
    Second, we establish a genuine mechanical-stress-induced OA model of the rabbit TMJ. In the experimental rabbits, repetitive forced jaw opening (RFJO) 3 hours/day for 5 days was applied. By histological assessment of the TMJ articular tissues, partial eburnation of the articular cartilage, reactive marginal proliferation of the articular cartilage chondrocytes and nested proliferation of chondrocytes in the subchondral bone area were observed at 7 days after the RFJO period. Furthermore, apoptotic chondrocytes were observed in the cartilage degradation area at 7 days after the RFJO period. And nitrotyrosine, a marker of NO production, and MMP-3, a key factor of cartilage ECM degradation, were observed where chondrocyte apoptosis was evident. These results suggest the RFJO protocol without any surgical intervention can induce evident OA-like lesions in the rabbit TMJ, and cartilage degradation in OA may be induced via chondrocytes apoptosis. This OA model may greatly contribute to the elucidation of the cartilage degradation mechanism in TMJ OA.

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  • 軟骨成長因子エコジェニン/CTGFによる生体デザインを目指す研究

    Grant number：13877311  2001 - 2002

    日本学術振興会  科学研究費助成事業  萌芽研究

    滝川 正春, 西田 崇, 久保田 聡, 中西 徹

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    Grant amount：\1700000 （ Direct expense: \1700000 ）

    ・ヒト軟骨細胞様細胞株HCS-2/8では、低酸素下では、エコジェニン/CTGFのmRNAと蛋白の増加が起こり、MMPsとTIMPとの比がmRNA並びに蛋白レベルで上昇した。即ち、低酸素が軟骨組織のリモデリングを促し軟骨形成を促進することを示唆した。
    ・エコジェニン/CTGFによる生体デザインを目指す一つの手法として、同因子の発現を転写レベルで調節する方法がある。そこで、軟骨由来HCS-2/8細胞におけるCTGFの構成的高発現を支えている領域を探索し、既知のTGF-β応答領域以外に新規のエレメントであるtranscription enhancer dominat in chondrocytes(TRENDIC)を見いだした。また、HCS-2/8細胞の核抽出液中にこのTRENDICに結合する軟骨特異的核内因子が存在することを見いだした。さらに、HCS-2/8細胞のcDNA発現ライブラリーを作成し、TRENDICと結合するタンパク質を3種類クローニングした。
    ・CTGFは成長軟骨細胞に対しては分化を肥大化まで促進するが、関節軟骨細胞に対してはプロテオグリカンやII型コラーゲン合成を促進するものの肥大化までは促進しないことを見いだし、内軟骨性形成だけでなく関節軟骨の形成にも有用であることを示した。
    ・骨折時に肥大軟骨細胞だけでなく、幼弱な骨芽細胞がエコジェニン/CTGFを発現することから同因子を膜性骨化を促進する手段としても用い得ることを示した。
    ・エコジェニン/CTGFに特徴的な4つのモジュールについて各モジュール毎の組み換え体蛋白質を、Brevibacillus choshinensisを用いて作成し、軟骨細胞、血管内皮細胞等に対する作用を検討し、モジュール毎に異なる生物活性があることを見いだした。
    以上の知見はエコジェニン/CTGFにより生体デザインを目指すための萌芽的研究として貴重な情報を提供したものと言える。

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  • Investigation of mechanism of connective tissue growth factor (CTGF) as a molecular target against cancer-induced bone destruction

    Grant number：13672093  2001 - 2002

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    SASAKI Akira, NAKANISHI Toru, TAKIGAWA Masaharu

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    Grant amount：\3600000 （ Direct expense: \3600000 ）

    Osteoclastic bone resorption plays an important role on cancer-induced bone disease likes bone metastases or cancer bone invasion. We previously reported that administration of antibody against connective tissue growth factor (CTGF) inhibited osteolytic lesions in nude mice bone metastasis model. It is suggested that inhibition of CTGF has a possibility of therapeutic use for the treatment of the cancer induced bone disease. However, the relationship between osteoclastic bone resorption and CTGF has been still unknown. In the present study, we examined the mechanism of CTGF on osteoclastic bone resorption to know whether we could use CTGF as a molecular target against the cancer-induced bone disease.
    Immunohistologically, the expression of CTGF protein was observed at bone-marrow stromal cells and osteoclasts, and especially localized at cytoplasm around the nuclei of osteoclasts in murine bone marrow culture system in vitro. CTGF anti-sense oligonucleotide (AS-CTGF) suppressed osteoclast formation, but did not inhibit mature osteoclastic bone resorption on dentin slice in vitro. AS-CTGF suppressed the expression of ODF (RANKL) mRNA in bone marrow /stromal cell line ST2, but did not affect the OCIF mRNA expression. Next, we examined the bone metabolism in nude mice subcutaneous implanting CHO cells transfected with CTGF gene. In spite of over-production of CTGF, systemic hypercalcemia was not observed in nude mice. And there is no difference of the tumor growth and body weight loss between the nude mice transfected with the transfectants and non-transfectant.
    It is well known that many growth factors store in bone matrices. Release of these growth factors like TGF-β by cancer-induced bone resorption probably regulates the biological events in the bone microenvironment. TGF-β dose-dependently increased the expression of CTGF mRNA of not only human breast cancer cells line MDA-231, but also ST2 cell. This indicates that TGF-β might regulate the CTGF expression of local bone resorption sites as paracrine factor. From these results, CTGF may play an important role on the local bone resorption site, and the inhibition of CTGF expression may be useful therapy for local bone destruction induced by cancer.

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  • MMP-3転写調節部位遺伝子多型からみた顎関節症の予後に関する分子遺伝学的研究

    Grant number：13672033  2001 - 2002

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    水口 一, 滝川 正春, 矢谷 博文, 窪木 拓男, 藤澤 拓生

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    Grant amount：\4000000 （ Direct expense: \4000000 ）

    MMP-3遺伝子のプロモーター領域の多型(5A/6A)と関節疾患感受性との関連性を明らかにすることを目的として遺伝子多型解析を検討した.まず,本年度は遺伝子多型解析に先立ち,本研究計画に対して岡山大学歯学部倫理委員会の承認を得る必要があった.そのため,平成13年11月から岡山大学歯学部倫理委員会の承認を受けた後,岡山大学歯学部附属病院第一補綴科に顎関節部の疼痛,機能障害を主訴に来院し,本研究の趣旨を文書にて説明し自発的同意の得られた被検者から一律3mlの血液採取を行った.
    平成14年1月30日現在での被検者数は,男性18名,女性26名の計44名であり,これら被検者の血液よりDNAの抽出を行った.このDNA抽出に関する手法は確立し得た.
    現在,抽出されたDNAから、MMP-3プロモーター領域の対立遺伝子の多型(variable number of tandem repeat : VNTR)ならびにIX型コラーゲンα3鎖の遺伝子多型(SNPs)を検討すべく,Ye et al.(1995)の方法ならびにPaassiltaらの方法に従い、PCR産物に対してTthlllI酵素処理を応用し,被検者個々の対立遺伝子の多型を明らかにした.
    その結果,現在集積された被検者数では,遺伝子多型と関節疾患感受性との間に統計学的に有為な関連性を見いだすことはできなかった.しかしながら,現段階では被検者数が少なくtype II errorが生じている可能性があり,今後も被検者数の継続的蓄積が必要となると考えられた.

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  • Gene therapy for temporomandibular joint osteoarthritis

    Grant number：12557169  2000 - 2002

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    KUBOKI Takuo, NAKANISHI Tohru, TAKIGAWA Masaharu, FUJISAWA Takuo, KASAI Teruo, YATANI Hirofumi

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    Grant amount：\12000000 （ Direct expense: \12000000 ）

    The purposes of this research are to clarify the mechanism of cartilage degradation in osteoarthritis (OA) and to investigate the possibility of gene therapy for articular cartlige restoration using connective tissue growth fector (CTGF).
    First, we establish a genuine mechanical-stress-induced OA model of the rabbit TMJ. In the experimental rabbits, repetitive forced jaw opening (RFJO) 3 hours/day for 5 days was applied. By histological assessment of the TMJ articular tissues, partial eburnation of the articular cartilage, reactive marginal proliferation of the articular cartilage chondrocytes and nested proliferation of chondrocytes in the subchondral bone area were observed at 7 days after the RFJO period. These results suggest the RFJO protocol without any surgical intervention can induce evident OA-like lesions in the rabbit TMJ, and this OA model may greatly contribute to the elucidation of the cartilage degradation mechanism in TMJ OA.
    Second, we investigated the effects of CTGF/Hcs24 transduced by recombinant adenoviruses on the rabbit articular cartilage (RAC) cells in vitro. When RAC cells were infected with adenoviruses caontaining the CTGF/Hcs24 gene, RAC cells expressed CTGF/Hcs24 mRNA and produced CTGF/Hcs24 protein. RAC cells synthesized more proteoglycan than the control cells.

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  • Investigation of the intracellular function of human ecogenin/CTGF, a chondrocyte-derived growth factor.

    Grant number：12671807  2000 - 2001

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    KUBOTA Satoshi, NAKANISHI Tohru, TAKIGAWA Masaharu

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    Grant amount：\3400000 （ Direct expense: \3400000 ）

    1) Evaluation of the cell-cycle modification effects of overexpressed CTGF : We overexpressed CTGF in a monkey kidney-derived Cos-7 cell line. Twelve hours after DNA transfection, accumulation of CTGF was observed at a particular perinuclear spot. Double staining of the cells with an anti-α-tubulin antibody indicated that it might be centrosome. Afterwards, CTGF accumulation became more prominent at 24 h posttransduction, which was accompanied by abnormal cell morphology with losing attachment and drastic increase of DNA content. These characteristics corresponded to those of cells in G2-M phases of cell cycle. Indeed, such findings were quite similar to those induced by colchicine, which halts mitosis at the M-phase. Since cell proliferation was rather retarded, CTGF was thought to arrest, or delay the cell cycle. Next, we examined the intracellular distribution of CTGF in vivo by immunohistochemical analysis of growth cartilage. Then, it was observed that CTGF accumulated in the same spot of hypertrophic chondrocytes which had stopped proliferation. We are going to transduce a cell line by a CTGF expression plasmid and analyze its gene expression pattern by a macro array system.
    2) Relationship between the modular structure and cell cycle modification effects of CTGF : CTGF consists of 4 conserved modules. In order to clarify which module is responsible for the findings above, a variety of plasmids that express CTGF deletion mutants were constructed. Using these plasmids, it has been uncovered that IGFBP module at the N-terminus is dispensable for the cell cycle modification effect, and that VWC plays a crucial role in the perinuclear accumulation of CTGF. Successful production of independent modular proteins was also carried out.
    3) Pursuit of intracellular target/receptor of CTGF : By means of CTGF-affinity column chromatography, we purified a CTGF-binding protein from cytosolic extract, determined a partial amino acid sequence, and identified it as a cytoskeletal protein.

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  • Analysis of gene expression in chondrocytes using DNA microarrays (DNA chips)

    Grant number：12671806  2000 - 2001

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    NAKANISHI Tohru, OHYAMA Kazumi, TAKIGAWA Masaharu

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    Grant amount：\3500000 （ Direct expense: \3500000 ）

    1) Gene expression in a pre-chondrocytic cell line ATDC5 was analyzed by using DNA microarrays. Several genes showed significant difference of expression level between undifferentiated and differentiated stage of ATDC5 cells.
    2) Gene expression in RA (rheumatoid arthritis)- or OA (osteoarthritis)-derived synoviocytes was analyzed by using DNA microarrays. The expression of STAT, PKC, caspase and IGFBP was upregulated in OA, and the expression of CDC25, RHO and FGF7 was up-regulated in RA. The expression of c-fos and c-jun was also up-regulated in RA. Immunostaining showed that apoptosisrelated caspase-9 was highly expressed in OA-derived synoviocytes and cartilage tissues.
    3) Gene expression in a chondrosarcoma-derived chondrocytic cell line, HCS-2/8 was analyzed by using DNA microarrays.The expression of several MAP kinases was up-regulated by the addition of CTGF. We found that CTGF stimulated the proliferation of HCS-2/8 cells through Erk, and the differentiation of HCS-2/8 cells through p38 MAPK.
    4) CTGF-overexpressed transgenic mice were prepared by injection of expression vectors in which CTGF was expressed under the control of type XI collagen promoter into fertilized eggs. The expression of exogenous CTGF was observed in the cartilage tissues of transgenic mice, but its endogenous expression was decreased in transgenic mice. It was also showed that transgenic mice had the phenotype of dwarfism with decreased bone density.

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  • Molecular cloning of the factors that biologically accelerate reparative dentin formation

    Grant number：12470418  2000 - 2001

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    KUBOKI Takuo, TAKIGAWA Masaharu, TAKASHIBA Shougo, SONOYAMA Wataru, KANYAMA Manabu, NAKANISHI Tohru

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    Grant amount：\13800000 （ Direct expense: \13800000 ）

    1. Gene delivery to cultured cells
    We prepared recombinant adenovirus vector carrying beta-galactosidase gene. Mouse osteoblast-like cells, MC-3T3 -E1, were cultured with this vector. As a result, almost all cells were transfected with beta-galactosidase gene.
    2. Localization of known factors (TGF-beta 1 and CTGF) in vivo animal model
    Localization of TGF-beta 1, that is supposed to be involved in reparative dentinogenesis, and CTGF were confirmed with immunohistochemical staining in animal (wister rat) experimental model. As a result, in 2 weeks from tooth reduction reparative dentin-like tissues were observed, and strong staining of TGF-beta 1 and CTGF were observed around these tissues.
    3. Gene expression of TGF-beta 1 and CTGF in cultured cells stimulated with proinflammatory factors
    MDPC-23, mouse-derived odontoblast-like cells were used in this study. The cells were stimulated with IL-1 beta and bacterial LPS. Changes in CTGF and TGF-b1 genes expression were examined by RT-PCR. As a result, MDPC-23 cells were expressing the CTGF and TGF-beta 1 genes coastitutively, and both factors increased CTGF gene expression and decreased TGF-b1 gene expression in the odontoblast-like cells (MDPC-23) within one-day period after stimulation.
    4. Effect of TGF-beta 1 and CTGF to cultured cells
    The effects of rCTGF and rTGF-beta 1 on cell proliferation were determined by the MTT assay. rTGF-beta 1 tended to decrease the proliferation dose-dependently, whereas effect of rCTGF was not evident. Next, to investigate the effects of rCTGF on calcification of MDPC-23 cells, cells were cultured with medium containing rCTGF. Sequential addition of AA and b-GP up-regulated the ALPase activity, while addition of rCTGF had no obvious effects.

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  • Development of analytical method for each domain of CTGF/ecogenin and its clinical application.

    Grant number：12557154  2000 - 2001

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    TAKIGAWA Masaharu, NISHIDA Takashi, KUBOTA Satoshi, NAKANISHI Tohru, MUKUDAI Yoshiki

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    Grant amount：\13200000 （ Direct expense: \13200000 ）

    Expression vectors for IGF binding protein-like(IGFBP), von Willebrand type C repeat(VWC), thrombospondin type I repeat(TSP1) and C-terminal(CT) domains of CTGF/ecogenin were constructed and their recombinant proteins were produced.
    Plasmids of CTGF lacking 1 or 2 domains were constructed and introduced into HeLa cells. Consequently, HeLa cell lines producing these proteins were established.
    Using the recombinant proteins, epitopes of six monoclonal antibodies and two polyclonal antibodies were determined. Three types of ELISA systems were developed.
    After production, CTGF was processed before it was secreted out of cells.
    CTGF was found to be a hypoxia-induced angiogenic factor, tumor angiogenesis factor and mechanical stress-induced factor. The ELISA systems described above could be used for diseases related with these phenomina.

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  • Ex Vivo Gene Delivery Using an Adenovirus Vector in Treatment for Dental Implant

    Grant number：12470419  2000 - 2001

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    KANYAMA Manabu, NAKANISHI Tohru, TAKIGAWA Masaharu, KUBOKI Takuo, ARAKAWA Hikaru

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    Grant amount：\8200000 （ Direct expense: \8200000 ）

    The purpose of this study was to contribute to shortening the healing period of the dental implant and expanding its application by ex vivo gene delivery using an adenovirus vector. It has been well-documented that connective tissue growth factor (CTGF) is up-regulated in the healing process at the bone fracture site in vivo and known as a potent stimulator for the proliferation and differentiation of osteoblasts in vitro. Therefore, CTGF gene transfer to the osteoblasts could be a promising strategy to accelerate bone formation. First, we investigated the possibility of recombinant adenovirus to transfer CTGF genes to a mouse osteoblastic (MC3T3-E1) cell line in vitro. Recombinant adenovirus encoding the LacZ gene and the human CTGF gene with CAG promotor (Ax1CACTGF) were applied to the MC3T3-E1 cells with 5, 10 and 50 multiplicity of infection (MOI). As the result, the MOI 50 transfection dosage produced almost 80% X-gal staining of the cells without any obvious cell damages and Ax1CACTGF transfection caused a marked up-regulation in CTGF mRNA expression and CTGF protein even 7 days after transfection. Second, we investigated the spatial and temporal expression of CTGF in the rat tooth extraction sockets to know the mechanisms of new alveolar bone formation. As the result, CTGF was expressed in the endothelial cells migrating into the granulation tissue at the sockets during 4 days after tooth extraction. Osteoblast-like cells proliferated in the sockets with CTGF expression at 4, 7, 10 and 14 days after extraction. Finally, we tried the ex vivo gene delivery, but we could not isolate osteoblasts from the defects of rat alveolar bone.
    Based on these findings, adenovirus-mediated CTGF gene transduction to the cultured osteoblast-like cells was highly successful. However, in order to do the ex vivo gene transfer, it is necessary to develop the new methods of isolating osteoblasts.

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  • Investigation of the regulatory mechanism of gene expression of human ecogenin/CTGF, a chondrocyte-derived growth factor.

    Grant number：11671841  1999 - 2001

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    OHYAMA Kazumi, NAKANISHI Tohru, TAKIGAWA Masaharu, KUBOTA Satoshi

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    Grant amount：\3600000 （ Direct expense: \3600000 ）

    1) Research on transcriptional control of ecogenin/CTGF gene expression : We constructed a series of chimeric reporter gene constructs, in which the human CTGF promoter and its deletion mutants were linked upstream of firefly luciferase genes. Using these constructs, we comparatively analyzed their promoter activities via transient expression assay in chondrocytic HCS-2/8 cells. Then, we found a 110-bp DNA segment located at 88 bp-upstream of the transcription initiation site as a critical determinant of the enhanced CTGF gene expression in HCS-2/8 cells. Moreover, we found two enhancer elements that were active in HCS-2/8 cells. One of them was a known TGF-β response element, whereas the other was a novel one discovered in this study. Mutation of either element resulted in drastic decrease of the promoter activity in HCS-2/8 cells. It is especially interesting that binding counterpart(s) of the latter latter element was found to be present specifically in HCS-2/8 cells.
    2) Research on post-transcriptional control of ecogenin/CTGF gene expression : We uncovered the strong repressive effect of the 1 kb-long 3'-untranslated region (UTR) of the ecogenin/CTGF gene on gene expression by comparatively evaluating the luciferase gene expression with or without the cis-linked 3'-UTR. Furthermore, we could identify an 84 base repressive cis-element by deletion analysis based on computer-associated structural prediction. Since this RNA element formed a stable secondary structure in solution, and the repressive function was highly dependent on the secondary structure forming potential, we entitled this element "cis-acting element of structure-anchored repression (CAESAR). Also recently, multiple stem-loop structure has been observed to be the structural determinant of CAESAR function. CAESAR did not display any effect outside of the transcribed region, and it did not affect the intracellular distribution of mRNA linked in cis. Therefore, CAESAR is thought to act at a step of mRNA translation without affecting the nuclear export of mRNA.

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  • アデノウイルスベクター法を用いた早期osseointegrationの獲得

    Grant number：11877338  1999 - 2001

    日本学術振興会  科学研究費助成事業  萌芽的研究

    李 起学, 滝川 正春, 中西 徹, 窪木 拓男

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    Grant amount：\2200000 （ Direct expense: \2200000 ）

    休止期や分裂増殖の遅い細胞へも高い効率で遺伝子導入が可能であり,in vivo遺伝子導入が容易な,アデノウイルスベクター法を用い,アデノウイルスベクターに骨形成能が高いCTGF, TGF-βの遺伝子を組み込む方法を用い,続いて,ラット脛骨にアデノウイルスベクターを投与し,周囲組織(骨芽細胞,間葉系細胞)に感染,遺伝子導入させることで,持続的にそれらの遺伝子を発現させ,早期osseointegrationの獲得を試みることを目的とした実験を行ってきた。
    前年度において,アテロコラーゲンとウイルスベクターの複合化と,複合化したウイルスベクターのin vivo LacZ遺伝子導入を行った。しかし導入効率が低く他のキャリアを用いた実験系が必要であると考えられた。そこで本年度はポリ乳酸や他の高分子生体材料をキャリアとして用いウイルスベクターと複合化を行いin vivo実験を行った。
    1.ポリ乳酸とウイルスベクターの複合化
    ポリ乳酸とウイルスベクター液を混ぜ凍結乾燥を行い,複合化させることに成功した。
    2.複合化したウイルスベクターのin vivo LacZ遺伝子導入
    ラット脛骨内に1で作製したLacZ遺伝子を発現するアデノウイルスベクターを注入し,経時的にラットを屠殺し,脛骨におけるLacZ遺伝子発現をX-gal染色にて観察したところ,ポリ乳酸を用いても導入効率の上昇にはつながらなかった。
    3.ウイルスベクターの他臓器への感染の有無
    2のラット屠殺時,固定直前に気管,肝臓,膵臓,腎臓,骨格筋を摘出し,total RNAを抽出し,LacZに対するprimerを用い,RT-PCRを行ったところ,他臓器にLacZ遺伝子の発現は認められなかったことから,ウイルスベクターの他臓器への影響がないことが確認できた。

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  • 軟骨由来成長因子エコジェニン/CTGFを用いた歯周組織再建への試み

    Grant number：11877324  1999 - 2000

    日本学術振興会  科学研究費助成事業  萌芽的研究

    滝川 正春, 西田 崇, 久保田 聡, 中西 徹

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    Grant amount：\2100000 （ Direct expense: \2100000 ）

    1.歯根膜線維芽細胞株(MPL)にエコジェニン/CTGF作用させると、骨芽細胞と共通した分化マーカーであるI型コラーゲン、オステオカルシン、オステオポンチン、アルカリホスファターゼ等のmRNAの発現が亢進することは昨年度見いだしたが、本年度は新たに骨膜と歯根膜にのみ発現し、骨芽細胞に分化すると発現レベルが低下するペリオスチン遺伝子の発現がエコジェニン/CTGFの作用により亢進することを見い出した。すなわち、エコジェニン/CTGFは歯根膜線維芽細胞に対しては骨芽細胞にtransdiffeentiationさせるのではなく、歯根膜線維芽細胞としての分化機能の発現を特異的に誘導することが明らかとなった。
    2.TGF-β、BMPおよびIGF-Iにより骨芽細胞株Saos-2においてエコジェニン/CTGFの発現が亢進することが分った。また、歯根膜線維芽細胞MPLにおいてもTGF-βによりエコジェニン/CTGF発現の亢進を見い出した。
    3.β-ガラクトシダーゼ遺伝子をマーカーとして組み込んだ非増殖性アデノウイルスベクターを顎関節腔内に直接注入することにより、関節軟骨に遺伝子導入が可能であった。また、熱ショックタンパク70遺伝子をマーカーとして組み込んだ非増殖性アデノウイルスベクターを培養細胞に感染させ熱ショック刺激で発現することからこのベクターが有用であることを確認した。
    4.エコジェニン/CTGF遺伝子を非増殖性アデノウイルスベクターに組み込み、マウス骨芽細胞株MC3T3-E1細胞への遺伝子導入してエコジェニン/CTGFの産生能を検討した。その結果、MC3T3-E1細胞にはこの方法で効率よく遺伝子導入が可能で、また遺伝子発現も少なくとも7日間継続することがわかり、その有用性を確認できた。

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  • Studies on the mechanism of actions of a cartilage-derived pleiotrophic growth factor, ecogenin/CTGF - Molecular cloning of its receptors and mechanism of inter- and intra signal transduction -

    Grant number：10470389  1998 - 2000

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B).

    TAKIGAWA Masaharu, NISHIDA Takashi, HATTORI Takako, NAKANISHI Tohru

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    Grant amount：\13300000 （ Direct expense: \13300000 ）

    1) Specific receptors for ecogenin/CTGF were found on chondrocytes, osteoblasts and vascular endothelial cells. Its molecular weight was about 240 kDa.
    2) Specific binding of radiolabeled ecogenin/CTGF for chondrocytes decreased as the cells differentiated.
    3) In chondrocyte culture system, ecogenin/CTGF bound cell surface heparan sulfate proteoglycans after secreted and was then released, suggesting that it is a matricrine factor.
    4) Ecogenin/CTGF stimulated phosphorylation of ERK and p38MAPK in chondrocytes. Using specific inhibitors, we found that ecogenin/CTGF promoted the proliferation and differentiation of chondrocytes through ERK and p38MAPK pathways, respectively.
    5) Two binding proteins for ecogenin/CTGF were purified from human chondrocytic cell line HCS-2/8. The one was 42 kDa protein of which N-terminal amino acid sequence corresponded to that of γ-actin and the other was 50 kDa protein of which N-terminal amino acid sequence corresponded to that of cytokeratin.
    6) When ecogenin/CTGF was overexpressed in Cos-7 cells, it localized around centrosome. C-terminal fragment was also found in cells.
    These findings suggest that ecogenin/CTGF not only acts as a paracrine and matricrine factor through its specfic receptors but also functions through an alternative intracellular pathway.

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  • Effect of mechanical stress on chondrocytes metabolism

    Grant number：10470415  1998 - 1999

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    KUBOKI Takuo, HATTORI Takako, TAKIGAWA Masaharu

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    Grant amount：\11300000 （ Direct expense: \11300000 ）

    To clarify the mechanism of cartilage degradation induced by mechanical stress, we investigated the influence of cyclic tension force (CTF) on the metabolism of cultured chondrocytes, The chondrocytes were exposed to CTF by using Flexercell strain unit. Five or 15 kPa of high frequency CTF significantly inhibited the syntheses of DNA, proteoglycan, collagen and protein. Fifteen kPa of high frequency CTF induced the expression of interleukin-1 (IL-1), matrix metalloproteinase (MMP)-2 and -9 mRNA, and increased the production of pro-and active-Mmp-9. the degradation of proteoglycan was inhibited by MMP Inhibitor, indicating that MMPs are involved in the degradation of proteoglycan induced by high frequency CTF.
    Moreover reducing the frequency of CTF from high to low decreased the inhibition of proteoglycan synthesis. These findings suggest that the CTF frequency is one of the key determinants of the chondrocyte metabolism. Low magnitude CTF, whether high or low frequency, did not cause the gene expression of cartilage degradation factors, suggesting that this magnitude of CTF causes only minor change of cartilage matrix. High magnitude and frequency CTF caused the gene expression of IL-1 and MMP-9, followed by increases in the production of MMP-2 and -8 protein suggest that excessive and continuous cyclic mechanical stress induces the production of IL-1 and MMP-9, resulting in cartilage degradation.

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  • The cloning and application of growth factors in restorative dentine

    Grant number：10470417  1998 - 1999

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    KANYAMA Manabu, SUZUKI Kouji, KUBOKI Takuo, TAKIGAWA Masaharu

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    Grant amount：\11500000 （ Direct expense: \11500000 ）

    This study first sought to find unknown genes that expressed specifically to be made the restorative dentine by odontblast. Next, to confirm that foreign genes can be transferred to dental pulp of rats and to clarify the in vivo transfer availability of the adenovirus vectors.
    When tooth was prepared the cavity by diamond points, we detected the specific 14 clones from dental pulp by subtractive hybridization.
    Recombinant adenovirus harboring LacZ gene was injected into the prepared tooth cavity of 6-week-old Wistar rats. At 1week after injection, the tooth was dissected and X-gal staining examined the expression of delivered LacZ. To investigate the expression of transferred gene in other organs, total RNA was extracted from liver, kidney, heart, and brain and expression of LacZ mRNA were analysed by RT-PCR. Expression of LacZ was observed a few odontblasts in the cavity. In the other organs, expression of the delivered transgene was not observed. Based on these findings, direct gene delivery into the tooth cavity using adenovirus vector is feasible as an effective in vivo method.

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  • Development of inhibitors for a angiogenesis factor CTGF and its application for angiogenetic diseases

    Grant number：10557165  1998 - 1999

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    TAKIGAWA Masaharu, INOUE Miho, HATTORI Takako, NAKANASHI Tohru, TAMATANI Takuo

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    Grant amount：\13700000 （ Direct expense: \13700000 ）

    1) As inhibitors for connective tissue growth factor (CTGF), a polyclonal antibody was raised by immunizing a synthesis CTGF fragment into rabbit. In addition, monoclonal anti-CTGF antibodies were also prepared.
    2) Recombinant CTGF (rCTGF) promoted the adhesion, proliferation and migration of the vascular endothelial cells and these effects were inhibited by anti-CTGF antibody.
    3) rCTGF markedly induced the tube formation of vascular endothelial cells, and this effect was stronger than that of basic fibroblast growth of vascular endothelial growth factor.
    4) Application of rCTGF to the chicken chrioallantoic membrane (CAM) resulted in gross angiogenic response and the effect was inhibited by anti-CTGF antibody. rCTGF injected with collagen gels into the back of mice induced strong angiogenesis in vivo.
    5) Among three cell lines (breast cancer cell line MDA231, fibrosarcoma cell line HT1080 and squamous carcinoma cell line A431), the ability to produce CTGF was highest in MDA231 and lowest in A431 and was parallel to their ability to form angiogenic tumors in nude mice. Anti-CTGF antibody inhibited tumor-induced angiogenesis in CAM.
    6) CTGF was present in synovial fluid in patients with rheumatoid arthritis which is an angiogenic decease.
    7) CTGF was expressed in the infarct zone of experimentally induced myocardial infarction in rats.
    8) Human anti-CTGF antibodies were raised in transgenic mice producing human type antibody. One of them inhibited bone metastasis of MDA231 tumors which produce much CTGF.
    These findings indicate that CTGF is a novel, potent angiogenesis factor which functions in multi-stages in physiological and pathological angiogenesis and suggest that anti-CTGF antibody can be used as an inhibitor for angiogenesis.

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  • INVESTIGATION OF MECHANISM OF BONE METTASTASIS AND MOLECULAR CLONING OF BONE METASITASIS RELATED GENE

    Grant number：09470454  1997 - 1999

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    MATSUMURA Tomohiro, SASAKI Akira, NAKANISHI Toru, TAKIGAWA Masaharu

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    Grant amount：\15400000 （ Direct expense: \15400000 ）

    Bone is one of the most common sites of metastasis in human cancer. The occurrence of osteolytic bone metastases causes serious morbidity due to intractable bone pain, pathological fractures, hypercalcemia and nerve compression syndromes declining the quality of life of cancer patients. Despite of the importance of these clinical problems, there is little information about the mechanism of bone metastases.
    1. Establishment of Bone metastasis model induced by Oral Squamous Cell Carcinoma (SCC)
    Several Oral SCC cell lines (HSC-2, 3, 4, Ho-1N1, HO-1u1, KB) were tested whether intracardiac injection of them could form the osteolytic bone metastasis. Only HSC-2 and 3 established bone metastasis foci. Interestingly, HSC-2 metastasized to not only bone but also the muscle and fascia. To determine the factors related to the bone metastases, we compared the differences of the expression of genes, proteins and others of all these cell lines. Both cell lines commonly showed the secretion of MMP-2 and -9, the expression of the integrin α2 and the degradation of E-cadherin which were previously described as the related factors to bone metastases. Although these factors may play an important role of bone metastases, it could not be concluded on which these were specific factors of bone metastasis. Therefore, the combination of these metastatic factors must be very important. In the other hand, a metastasis suppressor gene, nm23 H1 (NDP kinase A) was closely correlated to these both cell lines and human breast cancer cell MDA-231 that could form bone metastases.
    2. In vivo selection of specific bone metastasis cell lines derived from Oral SCC
    Intracardiac injection of HSC-2 metastasized to bone and muscle-fascia. Therefore, we attempted to select the subclones expressing a specific ability of metastasizing to bone and muscle respectively using in vivo selection. Consequently, we obtained two bone metastasis specific cell lines, HSC-2 OL (osteolytic) and HSC-2-BF (osteoformative). However, the muscle metastasis specific cell line was not selected. The HSC-2-OL inhibited the growth of osteoblastic cell line MC3T3-E1 and stimulated the formation and activity of osteoclasts. Although other cell lines showed the expression of BMP-2 and 4 genes, and the production of PTHrP, HSC-2OL did not produce them. Moreover, differential display analysis among HSC-2, HSC-2-OL and HSC-2-BF presented that the gene expression of HSC-2-OL was remarkably different from other two cell lines that showed the similar gene expression pattern each other. However, specific genes relating the bone metastasis has not been obtained. There are few experimental animal model presenting osteofomative bone metastatic lesions. Therefore, HSC-2-BF may provide the adequate model to investigate the mechanism of bone formation in bone metastasis.

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  • Molecular cloning of the receptors for chondrosarcoma-derived chondrocyte growth factor Ecogenin/CTGF

    Grant number：09671893  1997 - 1999

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    NAKANISHI Tohru, OHYAMA Kazumi, HATTORI Takako, TAKIGAWA Masaharu, INOUE Miho

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    Grant amount：\3200000 （ Direct expense: \3200000 ）

    (1) Connective tissue growth factor (CTGF) was cloned from a chondrocyte-derived chondrocytic cell line, HCS-2/8 by differential display-PCR.
    (2) Recombinant CTGF (rCTGF) stimulated the proliferation, maturation and differentiation of chondrocytes.
    (3) Two types of receptors for CTGF were found on a chondrocyte-derived chondrocytic cell line, HCS-2/8. The receptor with high affinity was supposed to be cell adhesion molecules including integrins. The receptor with low affinity was supposed to be extracellular matrix compounds including proteoglycans.
    (4) The inhibitory experiments using signal inhibitors showed that intercellular signal transduction in HCS-2/8 cells caused by the stimulation of CTGF was mediated by MAP kinase-pathways including MEK and ERK.
    (5) CTGF-binding proteins were purified from membrane fractions and cytoplasmic fractions of HCS-2/8 cells with CTGF-conjugated affinity chromatography. As a result, four binding proteins (34, 44, 66 kDa from membrane fractions 50 kDa from cytoplasmic fractions) were purified from HCS-2/8 cells. The expression of these four proteins were regulated by the stimulation of CTGF, suggesting that they were functionally associated with CTGF.
    (6) The cDNA of tyrosine kinase-type receptors were cloned from HCS-2/8 cells using degenerate primers corresponding to the consensus sequences between tyrosine kinase-domains. The sequence analysis of these cDNA revealed that there were several types of tyrosine kinase-receptors including novel receptors in HCS-2/8 cells. The expression of these receptors were regulated by the stimulation of CTGF. In addition, CTGF-producing cells showed high level of expression of these receptors. These results suggest that they were functionally associated with CTGF.

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  • Basic Research of Gene Therapy for Joint Diseases

    Grant number：09470320  1997 - 1998

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    KUBO Toshikazu, TAKIGAWA Masaharu, SAWADA Kouhei

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    Grant amount：\9000000 （ Direct expense: \9000000 ）

    We evaluated the in vivo applicability of adenovirus-mediated gene delivery in order to consider the feasibility of gene therapy for human joint diseases.
    We directly injected vectors harbouring beta-galactosidase (beta-gal) or transforming growth factor (TGF)-beta1 gene into the joints of Hartley guinea pigs. Expressions of transduced beta-gal genes were examined by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining and reverse transcription- polymerase chain reaction (RT-PCR). The levels of TGF-beta1 which was delivered to the joint and then transferred to the joint fluid, were assessed by enzyme-linked immunosorbent assay (ELISA). LacZ expression was observed in almost the entire synovial tissues and in chondrocytes on the surface of degenerated cartilage. Un expected effects of the direct vector inj ection on the other organs were also examined, no expression of delivered gene was observed. Therefore, intraarticular direct injection would achieve gene delivery limited to the joint cavity, possibly eliminating unecessary systemic effects. TGF-beta1 levels in the joint fluid following the gene delivery had been significantly higher than the levels in the controls for 2 weeks.
    Direct gene delivery into the joint cavity is realistic with the in vivo gene delivery method using adenovirus vector, and it would be clinically applicable.

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  • アデノウイルスベクターを用いた遺伝子導入法による顎関節症の遺伝子治療の試み

    Grant number：09877351  1997 - 1998

    日本学術振興会  科学研究費助成事業  萌芽的研究

    滝川 正春, 中西 徹

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    Grant amount：\2000000 （ Direct expense: \2000000 ）

    1) 昨午度マーカー遺伝子としてβ-ガラクトシダーゼ遺伝子を組み込んだ非増殖性アデノウイルスベクターをヒト軟骨細胞様細胞株HCS-2/8細胞にin vitroで導入し、X-gal染色にて導入遺伝子が少なくとも3週間持続発現することを確認したが、今年度はまずウサギ膝関節軟骨細胞および顎関節軟骨細胞を初代培養し同様の実験を行った。即ち、両細胞にコンフルエントに達した二日後に上記のβ-ガラクトシダーゼ遺伝子を組み込んだりコンビナントウィルスをmoi20から50で感染させ遺伝子導入すると、導入遺伝子が少なくとも3週間持続発現することをX-gal染色にて確認した。
    2) ウサギ膝関節軟骨細胞を用いて、インターロイキン-1が一酸化窒素を介してマトリックスメタロブロテイナーゼおよび線維芽細胞増殖因子を誘導することが関節炎発症の一機序であること見出した。すなわち、これらが遺伝子治療の一標的となる可能性を示唆する知見を得た。
    3) 昨年度は、β-ガラクトシダーゼ遺伝子を組み込んだ非増殖性アデノウイルスベクターをモルモットの膝関節腔内に注射し、X-gal染色にて滑膜のほとんど全域と一部の変性軟骨表層に遺伝子が導入されていることを明らかにしたが、本年度は同様の方法で、P-ガラクトシダーゼ遺伝子を組み込んだりコンビナントウィルス4.8x10^7pfuをモルモットの顎関節腔内に26ゲージ針で注射し、導入遺伝子の発現をX-gal染色で調べた。その結果、顎関節では膝関節とは異なり、側頭結節の関節表層と関節円盤の線維軟骨細胞と滑膜に遺伝子が導入され、少なくとも4週間に亘ってβ-ガラクトシダーゼ遺伝子が発現し続けることがわかった。なお、肝臓や腎等の他の臓器への導入遺伝子の拡散がないことをRT-PCRで確認した。したがって、本法を用いることにより、顎関節症の遺伝子治療が理論的に可能なことが証明された。

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  • The role of hcs-24, a newly isolated hypertrophic chondrocyte-specific gene, in endochondral ossification

    Grant number：08457490  1996 - 1997

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    TAKIGAWA Masaharu, HATTORI Takako, TAKAHASHI Kojiro, NAKANISHI Tohru

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    Grant amount：\1900000 （ Direct expense: \1900000 ）

    1) cDNA of hypertrophic chondrocyte specific gene hcs-24 was isolated. The nucleotide sequence of coding region of hcs-24 was completely the same as that of connective tissue growth factor (CTGF).
    2) Expression of hcs-24/ctgf in rabbit growth cartilage cells in culture was highest in hypertrophic stage. The gene expression in chondrocytic cells was stimulated by TGFbeta and BMP-2.
    3) Immunohistochemical techniques revealed that hypertrophic chondrocytes and endothelial cells in cost-chondral junctions of mouse ribs were stained with anti-CTGF antibody in vivo. Surface of and chondrocyte clusters in articular cartilge of arthritis were also stained with the antibody.
    4) During development of mouse embryos, mRNA level of hcs-24/ctgf reached a maximum at E7, decreased gradually and then increased again at E17.
    HCS-2/8 cells transfected with an hcs-24 expression vector grew rapidly than non-transfected cells. The abilities to proliferate and migrate of vascular endothelial cells transfected with expression vectors that generate anti-sense RNA of CTGF cDNA were markedly lower than those of control.
    6) Purified CTGF and recombinant CTGF stimulated the proliferation and proteoglycan synthesis of chondrocytes and alkaline phosphatase in chondrocytes and osteoblasts. The growth factor simulated the proliferation and migration of vascular endothelial cells. These effects were inhibited by anti-CTGF antibody.
    7) An ELISA system to measure Hcs-24/CTGF was established.
    8) Two types of specific binding sites of ^<125>I-rCTGF were identified on HCS-2/8 cells. The binding of ^<125>I-rCTGF to rabbit growth cartilage cells in culture was maximal in growth phase and decreased as they differentiated.
    9) Transgenic mice of OCNT/CTGF had skeletal disorder.
    These findings suggest that Hcs-24/CTGF synthesized by hpertrophic chondrocytes stimulates the proliferation and maturation of proliferative chondrocytes and hypertrophy of mature chondrocytes and induces angiogenesis into cartilage from bone, resulting in promotion of endochondral ossification. The factor may also be involved in organogenesis in embryos.

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  • Regulation of IGF-2 gene expression in human chondrosarcoma derived cell lines : HCS-2/8 and -2/A

    Grant number：08672124  1996 - 1997

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    TAKAHASHI Kojiro, TAKIGAWA Masaharu, HATTORI Takako

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    Grant amount：\2600000 （ Direct expense: \2600000 ）

    In chondrocytes without vascula, autocrine function of insulin-like growth factor-2 (IGF-2) is very important for the growth and differentiation. Regulation on the expression of IGF-2 gene (IGF-2) in human chondrosarcoma derived cell lines (HCS-2/8 and -2/A) was investigated in order to explore the function of IGF-2.
    In human chondrocytes, all four promoters of IGF-2 are expressed, and consensus binding sequenses to the transcriptional factors ; EGR1 (early growth response gene product 1), SP-1 (specificity protein-1) and WT1 (Wilms tumor suppresor), are localizing over the transcriptional regulation region of IGF-2 promoters. Although the expression of SP-1 is very slight in both of normal chondrocytes and HCS-2/8, EGR1 expression in HCS-2/8 was higher than that in normal chondrocytes and WT1 expression in HCS-2/8 was lower thatn that in normal chondrocytes. This suggests that the abnormal growth of chondrosarcoma-derived HCS-2/8 may be induced with the synergistic effect between a positive function of EGR1 and negative one of WT1 to the growth enhancement during the initial growth phase.
    The effects of ascorbic acid in HCS-2/8 were positive to the gene expression of IGF-2, H19 (tumore suppresor), EGR1, SP-1, WT1, type-10 collagen alpha1, aggrecan and alkaline phosphatase, but negative to that of type-2 collagen alpha1. These results suggest that the role of ascorbic acid in chondrocytes may be as a growth and differetiational factor during the phases to differentiation from growth.
    The imprinting status of IGF-2 in HCS-2/8 was paternal alleles for all the promoters, and seem to be independent directly on the excess gene expression. On CDKNIC (p57^<KIP2>) in the imprinting cluster over human chromosome 11p15.5 region, a lacking of PA in the PAPA-repeat was detected for the paternal allele in HCS-2/8, and the expressed allele was maternal.

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  • Molecular cloning of novel osteoneurotrophins and their application as therapeutic agents for bone and cartilage diseases

    Grant number：08557098  1996 - 1997

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    TAKIGAWA Masaharu, MAKISHIMA Fusao, TAKAHASHI Kojiro, NAKANISHI Tohru

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    Grant amount：\20100000 （ Direct expense: \20100000 ）

    1) Neurotrophin (NT) -3 stimulated the proliferation of osteoblastic cells by increasing binding of TRE and SRE to DNA via trk C.Ascorbic acid stimulated expression of NTs, especially NT-3, in osteoblasts.
    2) Cultured growth cartilage cells expressed NTs and osteocytes expressed NGF and trkA is culture. Expression of NF,BDNF and NT-3 in mouse periodontal ligament cellsincreased as they became confluent while expression of trks decreased.
    3) Expression of trkA and trkC and NGF and NT-3 increased 2 days after fracture of mouse long bones.
    4) hcs-24, which was isolated from the human chondrocytic cell line HCS-2/8 as a chondrocyte- (especially hypertrophic cohondrocyte) specific gene, encoded connective tissue growth factor (CTGF). Purified CTGF and recombinant CTGF stimulated proliferation of glia cells and induced neurite formation of PC12D cells. cTGF also stimulated the proliferation and differentiation of chondrocytes, differentiation of osteoblasts, the proliferation and migration of vascular endothelial cells. These findings indicate that Hcs-24/CTGF is a novel osteochondro-neurotrophin (OCNT).
    5) Immunohistochemical staining with an anti-CTGF antibody revealed that spinal nerves and trigeminal ganglion were highly positive and nerves in cortex and astroglias in hippocampus were also positive. In situ hybridization revealed that motor neuron and neuron in trigeminal ganglion expressed CTGF mRNA.Carbachol stimulated neurite formation of PC12D cells.
    6) Two types of specific binding sites of ^<125>I-rCTGF were identified on HCS-2/8 cells. MAP kinase was found to be involved in signal transduction in the cells.
    7) Transgenic mice of OCNT/CTGF had skeletal disorder.
    8) Both IGF-I and II,which are known to induce neurite formation, stimulated expression of differentiated phenotype of chondroxytes via their respective receptors.
    These findings suggest that the soluble factors mentioned above can be used as therapeutic agents for bone and cartilage diseases.

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  • Cloning and functional analysis of novel genes related to chondrocyte differentiation using the human chondrocytic cell lines

    Grant number：06454521  1994 - 1995

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for General Scientific Research (B)

    TAKIGAWA Masaharu, HATTORI Takako, NAKANISHI Tohru, TAKAHASHI Kohjiro

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    Grant amount：\7100000 （ Direct expense: \7100000 ）

    To isolate new functional and regulatory molecules, which play an important role in the process of endochondral ossification, we first characterized the newly established human chondrosarcoma cell lines (HCS) and established a model culture system on the proliferation and differentiation of rabbit growth cartilage cells. We then analyzed mRNAs expressed in HCS cell lines, normal rabbit chondrocytes and other types of cells using differential display-PCR.Consequently, we obtained 30 species of chondrocyte- of HCS-specific DNA fragments. Nucleotide sequences of 17 of 30 species derived from HCS cells were determined. Comparison of the base sequences revealed seven novel sequence tags and a few sequence tags showing homology with known DNA sequences. One of the sequence tags (tag no.24) showed high structural homology with the nucleotide sequence of connective tissue growth factor (CTGF) and the corresponding gene (hcs24) was selectively expressed in HCS cells and rabbit growth cartilage cells in culture but was not expressed in osteoblastic cells of osteosarcoma cells in culture. The expression of hcs24 in HCS cells was up-regulated by the addition of TGF-beta or BMP-2. During in vitro culture of rabbit growth cartilag cells, its expression reached a maximum at the stage corresponding to early hypertrophic chondrocytes in vivo. In situ hybridization revealed that hcs24 was expressed only in the hypertrophic chondrocytes of costal cartilage and the vertebral column in embryonic mice. Anti-sense oligonucleotides strongly inhibited the proliferation of HCS cells and increased their proteoglycan synthesis. The anti-sense oligomer also increased alkaline phosphatase activity in rabbit growth cartilage cells in culture. These results suggest that Hcs24 protein is produced by hypertrophic chondrocytes and that it promotes the proliferation of growth cartilage cells and suppresses their differentiation toward endochondral ossification.

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  • Expression and promoter-alternation of osteoblastic insulin-like growth factors

    Grant number：06671854  1994 - 1995

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for General Scientific Research (C)

    TAKAHASHI Kojiro, TAKIGAWA Masaharu, HATTORI Takako, NAKANISHI Tohru

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    Grant amount：\2200000 （ Direct expense: \2200000 ）

    Using a chondrocytic cell line HCS-2/8 derived from human chondrosarcoma, the quantitative analytical method adapting the RNase protection Assay (RPA) was developped in order to examine the expression and promoter-alternation of insulin-like growth factor genes. The probe of the RPA experiments was constructed for the promoters 2P-1,2P-3 and 2P-4 of IGF-2 and the promoters 1P-1 and 1P-2 of IGF-1, but the promoter 2P-2 of IGF-2 failed to be constructed because the transcriptional product was very little in HCS-2/8. Now, we continue to investigate the determination of detectable limitation of the RPA method using their probes, and we will retry to construct the probe asfter the accumulation of RT-PCR product for 2P-2 transcript.
    During the present developmental investigations, we found some new facts as following :
    1.The simultaneous expression of four promoters of IGF-2 were induced in HCS-2/8 and human normal chondrocytes.
    2.A defect of four base pair in the promoter 2P-4 transcript of IGF-2 in HCS-2/8 was observed at the 3'-end of exon 6, at which the position is upstream of 9 to 6 base from the translation-starting point. This defect may be due to the alternative splicing specific to the chondrosarcoma.
    3.Comparing with HCS-2/8 and human normal chondrocytes, we found a parallel correlation between IGF-2 and H19 (tumor reppressor gene) expressions.
    4.The restriction fragment length polymorphism of IGF-2 gene in HCS-2/8 suggested that only the paternal allele (s) existed at the genomic level, but the maternal imprinting allele was absent in the chondrosarcoma. This perhaps correlate with the tumor formation.

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  • Studies on the mechanism of endochondral ossification using a clonal chondrocyte like cell line newly established from a human chondrosarcoma - approach using the methods of cellular and molecular biology

    Grant number：03454429  1991 - 1992

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for General Scientific Research (B)

    TAKIGAWA Masaharu, ASADA Akira, ENOMOTO Motomi

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    Grant amount：\6000000 （ Direct expense: \6000000 ）

    1. HCS-2/8 cells produced both IGF-I and IGF-II and expressed mRNA of these growth factors. The cells had types I and II receptors for IGF. Both IGF-I and II stimulated proteoglycan synthesis. These findings suggest that both IGFs act as autocrine differentiation factors in maintaining a high level of proteoglycan synthesis in HCS-2/8 cells. In contrast to previous findings using other cell lines, we found that IGF-type II receptor on HCS-2/8 cells play an important role in signal transduction by IGF-II-stimulated proteoglycan synthesis.
    2. Basic FGF stimulated the proliferation of HCS-2/8 cells only in sparse culture and the cells produced large amount of bFGF, suggesting that overexpression of bFGF is involved in permanent growth of the cell line. TGF-beta stimulated DNA and proteoglycan syntheses in the cells. The factor supports the proliferation and differentiation of HCS-2/8 cells in serum-free medium.
    3. Using northern blotting and RT-PCR, we found that HCS-2/8 cells express many genes related to chondrocyte differentiation such as aggrecan core protein, collagen types II, X and XI, IGF-I and IGF-II and these receptors and vitamin D_3 receptor. Ascorbic acid induced alkaline phosphatase activity and its mRNA expression. It also induced hypertrophy of the cells.
    4. There were no detectable transcripts for the following proto-oncogenes: c-sis, c-met, c-src, c-lyn, c-fgr, c-ros, c-pim, and Blym. However, transcripts of 12 other proto-oncogenes (int-2, erbB, c-abl, c-raf-1, c-fyn, K-ras, H-ras, c-mos, c-myc, c-myb, c-fos, and c-jun) are readily detectable by Northern analysis. Two proto-oncogenes, c-fos and c-raf-1 had an elevated levels of transcripts as high as 10 and 3 folds, respectively, at the overconfluent phase in comparison with the earlier phases of culture, suggesting relation to hypertrophy.

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  • Purification of Receptors to Parathyroid Hormone from Cultured Chondrocytes and the Mechanism of its Signal Transduction

    Grant number：01571016  1989 - 1990

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for General Scientific Research (C)

    ASADA Akira, TAKIGAWA Masaharu, SUSZUKI Fujio

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    Grant amount：\2100000 （ Direct expense: \2100000 ）

    1) Parathyroid Hormone (PTH) receptors on cultured rabbit costal chondrocytes were demonstrated using HPLC-purified, radio-iodinated [Nle^<8,>-Nle^<18>, Tyr^<34>]bovine PTH- (1-34) amide. Both Growth Cartilage (GC) cells and resting cartilage cells were shown to have a single class of saturable, high affinity PTH binding sites with a dissociation constant of 0.6-0.7 nM. The number of receptors per cell was approximately 40,000-90,000 on GC cells. After crosslinking the receptors on these cells with the radioligand, One, major^<125>l-labeled band of 76 kDa was separated by SDS-PAGE.
    2) Treatment with retinoic acid, epidermal growth factor and fibroblast growth factor of rabbit costal chondrocytes decreased both proteoglycan synthesis and the number PTH receptors while treatment with insulin-like growth factor-I, dibutyryl cyclic AMP and transforming growth factor-beta resulted in increases in proteoglycan synthesis as well as in the number of PTH receptors. However, their affinity did not change by these treatments. The PTH-stimulated cyclic AMP level in chondrocytes pretreated with retinoic acid, epidermal growth factor and fibroblast growth factor was lower than that in control cells while the PTH-stimulated cvclic AMP level in chondrocytes pretreated with insulin-like growth factor-I and transforming growth factor-beta was higher tnan that in control cells. These observations suggest that the increase in the number of PTH receptors on chondrocytes is closely related with expression of the differentiated phenotype of chondrocytes and that the number of the receptors is a good marker of the differentiated phenotype of chondrocytes.
    3) Three clonal cell lines with responsiveness to PTH during more than 3 years, more than 58 passages in culture were established from growth cartilage of mouse ribs. Among the three clonal cell lines, a cell line, named MGC/T1.18, showed the highest responsiveness to PTH : The hormone increased intacellular cAMP level in the cells to 200 times that of control.

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  • Studies on mechanisms of proliferation, differentiation and calcification of chondrocytes using established clonal cell lines.

    Grant number：63480411  1988 - 1989

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for General Scientific Research (B)

    TAKIGAWA Masaharu, ASADA Akira

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    Grant amount：\6500000 （ Direct expense: \6500000 ）

    1) Three clonal cell lines with differences in responsiveness to parathyroid hormone (PTH), alkaline phosphatase activity and ability to produce an endothelial cell growth inhibitor(s) during more than 3 years in culture were established from growth cartilage (GC) of mouse ribs. MGC/Tl.17 cells had high activity of alkaline phosphatase, an ability to calcify and epidermal growth factor (EGF) receptors and responded well to epidermal growth factor, transforming growth factor beta. MGC/Tl.18 cells responded well to parathyroid hormone and produced sulfation factor. MGC/Tl.4 cells produced endothelial cell growth factor and sulfation factor. Glycosaminoglycan (GAG) syntheses in the three clonal lines were much lower than that of primary cultures of GC cells. The three clonal lines mainly synthesized type I collagen. Because of their different properties, these cell lines should be useful for studies on endochondral ossification, the actions of PTH on skeletal cells and anti-angiogenesis factors.
    2) A clonal cell line with cartilage phenotypes during more than 3 years in culture was established from a human chondrosarcoma. The clonal line, named HCS-2/8, formed synthesized cartilage-type proteoglycans and collagen types II and XI which are typical cartilage phenotypes. Like rabbit costal chondrocytes in primary culture, they also responded well to insulin-like growth factors I and II, transforming growth factor beta and retinoic acid. HCS-2/8 cells had low alkaline phosphatase activity and did not calcify in the absence of ascorbic acid but the enzyme activity increased markedly in the presence of the vitamin. The cells produced inhibitors of alkaline phosphatase and calcification. Because of these properties, the cell line should be useful for studies on endochondral ossification.

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  • Purification of cartilage-derived anti-tumor factor (CATF) and establishment of cell lines which produce CATF

    Grant number：61480387  1986 - 1987

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for General Scientific Research (B)

    TAKIGAWA Masaharu, SHIRAI Eiji, SUZUKI Fujio

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    Grant amount：\6500000 （ Direct expense: \6500000 ）

    1. Purification of cartilage-derived anti-tumor factor (CATF)
    CATF was extracted from fetal bovine cartilage with 1 M guanidine hydrochloride and parrially purified by acetone fractionation (45 - 65%), ultrafiltration (Molecular weight; 100-300k) and DEAE-Sepharose CL-6B column chromatography (eluted with 0.3 to 0.35 M NaCl at pH 8.0). The partially purified CATF strongly inhibited the growth of solid sarcoma 180 and B16 melanoma in vivo, the proliferation and DNA synthesis of bovine pulmonary artery endothelial (CPAE) cells in culture and B16 melanoma-induced angiogenesis in chick embryo chorioallantoic membranes (CAM). The specific activity of this partially purified CATF was about 70 times that of crude CATE when determined using its inhibitory action on DNA synthesis in CPAE cells in culture.
    2. Production of CATF by rabbit costal chondrocytes in primary culture.
    Serum-free medium conditioned by exposure to rabbit costal chondrocytes in primary culture specifically inhibited the proliferation and DBA synthesis of CPAE cells in Culture. The factor in conditioned medium (CM) also inhibited angiohenesis in CAM induced by B16 melanoma and growth of the tumor transplanted onto the CAM. These findings strongly suggest that rabbit costal chondrocytes produce CATF.
    3. Establishment of cell lines producing CATF.
    A cell line showing some phenotypes of growth cartilage, such as responsiveness to parathyroid hormone and high alkaline phosphatase activity was established from secondary cultures of mouse costal growth cartilage. Moreover, a cell line showing typical cartilage phenotypes was established from human chondrosarcoma. CM obtained from these cells inhibited the proliferation and DNA synthesis of CPAE cells in culture. The inhibition was specific for CPAE cells. Therefore, these cell lines are thought to produce CATF.

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  • 軟骨細胞の増殖・分化と骨形成におけるビタミンDの作用機作

    Grant number：61570884  1986

    日本学術振興会  科学研究費助成事業  一般研究(C)

    白井 栄二, 滝川 正春, 鈴木 不二男

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    Grant amount：\1800000 （ Direct expense: \1800000 ）

    1.ビタミンD欠乏のウシ胎仔血清添加培地で培養した対数増殖期のウサギ肋軟骨成長軟骨細胞に1×【10^9】Mの1α,25【(OH)_2】【D_3】を添加すると、DNA合成及び細胞増殖が促進されることを明らかにした。また、静止軟骨細胞に同濃度の1α,25【(OH)_2】【D_3】を添加すると、増殖促進効果はみられたものの成長軟骨細胞に対する効果と比べ軽度であった。一方、【10^(-9)】〜【10^(-7)】Mの24,25【(OH)_2】【D_3】を成長軟骨細胞及び静止軟骨細胞に添加してもDNA合成には影響がみられなかった。
    2.ビタミンD欠乏状態で9日間培養した成長軟骨細胞の細胞間基質はトルイジンブルー染色により著しいメタクロマジアを示したが、【10^(-9)】Mの1α,25【(OH)_2】【D_3】の存在下で培養すると軽度のメタクロマジアしかみられなかった。一方、24,25【(OH)_2】【D_3】はこの条件下ではメタクロマジアにほとんど影響を与えなかった。これらの事実は1α,25【(OH)_2】【D_3】が軟骨細胞の分化機能の1指標であるグリコサミノグリカン(GAG)合成を特異的に阻害することを示唆しているが、この点を確認する為、〔【^(35)S】〕硫酸の取り込みを指標として検討したところ、【10^(-9)】Mの1α,25【(OH)_2】【D_3】は成長軟骨細胞のGAG合成を著しく阻害した。一方、静止軟骨細胞のGAG合成はわずかにしか阻害しなかった。また、24,25【(OH)_2】【D_3】はこれらの細胞のGAG合成には影響を与えなかった。3.コンフルエントの状態の成長軟骨細胞に1α,25【(OH)_2】【D_3】あるいは24,25【(OH)_2】【D_3】を添加してもDNA合成に影響がみられなかった。4.コンフルエントの状態の成長軟骨細胞のGAG合成に対するビタミンDの影響を検討したところ、1α,25【(OH)_2】【D_3】は全く影響を与えなかったが、【10^(-7)】Mの24,25【(OH)_2】【D_3】は著しくGAG合成を促進した。以上の事実より1α,25【(OH)_2】【D_3】は十分に分化していない軟骨細胞の増殖を促進すると共にその分化機能発現をさらに促進することが明らかとなった。

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  • Bioassays for parathyrois hormone using clutures chondrocytes

    Grant number：60870013  1985 - 1987

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Developmental Scientific Research

    TAKIGAWA Masaharu, SHIRAI Eiji, TAKANO Teruko, SUZUKI Jujio

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    Grant amount：\3800000 （ Direct expense: \3800000 ）

    1. Bioassay for parathyrois hormone (PTH) using rabbit costal growth cartilage (RGC) celle in culture. A simple procedure of bioassay of PTH using ornithine decarboxylase induction obsarved 4 hr after PTH addition was developed. In this method, RGC cells in primary cultyres were suspended in hypotonic standard buffer and directely incubated wirh^<14>Cornithine. The simi-log dose-dependent curve using PTH preparation of MRC research Standard A was linear between 0.01 to 1 IU/ml. The actibeties of various synthetic analogs and framents of PTH determined by this method almost corresponded to those obtained by in vivo assay and renal afenylate cyclase assat.
    The stimulation of intracelluar cyclic AMP (cAMP) level obsearved 2-5 min after the addition of PTH was also found to be used as a new system fro the bioassay of PTH. Its semi-log dose-dependent curve was linear bvetween 10^<-9>M and 10^<-7>M. The activities of various synthetic analogs and fragments of PTH determined by this method also corresponded to those obtained by other assay. The change in cAMP level after PTH addition was too fast to be used as a procedure by which many samples were assayed at the same time, byt this problem was solved using isobutylmethylxamthine which maintained the PTH-stimulated cAMP level at least for 30 min.
    2. Establishment of a PTH-responsive clonal cell line from mouse growth cartilage. A clonal cell line that respond to PTH was isolated from a cell line established from secondary cultures of mouse growth cartilage. The change in the level of cAMP after addition of PTH to this clonal line was similar to that in primary cultures of RGC cells. The dose response vurce of change in the cAm@p level was also similat to that in RGC cells. However, ther extent of stimulation in the clonal cells was graster than that in RGC cells. The clonal cell line is now in passage 50 and is thought to be immortalized. Therefore, this cell line will be very useful for a simple, easy and time-sdabvign bioassay of PTH.

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  • From molecules to organisms （2024academic year） Third semester  - 金5～6