Updated on 2024/02/02

写真a

 
KAWATA Kazumi
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Assistant Professor
Position
Assistant Professor
External link

Degree

  • 博士(歯学） ( 2007.3   岡山大学 )

Research Interests

  • 細胞生物学

Research Areas

  • Life Science / Oral biological science

Research History

  • 岡山大学医歯薬学総合研究科   助教

    2015.4

    　 More details

  • University of Yamanashi   Department of Research Interdisciplinary Graduate School of Medicine and Engineering   Assistant Professor

    2012.4 - 2015.3

    　 More details

  • 岡山大学医歯薬学総合研究科   博士研究員

    2010.4 - 2012.3

    　 More details

  • 岡山大学医歯薬学総合研究科   助教

    2009.6 - 2010.3

    　 More details

 

Papers

  • Expression and function of CCN2-derived circRNAs in chondrocytes

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

    Journal of Cell Communication and Signaling   2023.9

    　More details

    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.

    Graphical abstract

    DOI： 10.1007/s12079-023-00782-7

    researchmap

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

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

    Kubota S, Kawaki H, Perbal B, Takigawa M, Kawata K, Hattori T, Nishida T.,

    J Cell Commun Signal.   17 ( 2 )   353 - 359   2023

    　More details

    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.

    PubMed

    researchmap

  • Molecular and Genetic Interactions between CCN2 and CCN3 behind Their Yin-Yang Collaboration Reviewed

    Satoshi Kubota, Kazumi Kawata, Takako Hattori, Takashi Nishida

    International journal of molecular sciences   23 ( 11 )   2022.2

    　More details

  • Odontoblast differentiation is regulated by an interplay between primary cilia and the canonical Wnt pathway Reviewed

    Kazumi Kawata, Keishi Narita, Ayako Washio, Chiaki Kitamura, Tatsuji Nishihara, Satoshi Kubota, Sen Takeda

    Bone   150   116001 - 116001   2021.9

    　More details

    Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.bone.2021.116001

    researchmap

  • Cellular communication network factor 3 in cartilage development and maintenance Reviewed

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

    Journal of Cell Communication and Signaling   2021.6

    　More details

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

    DOI： 10.1007/s12079-021-00629-z

    researchmap

    Other Link： https://link.springer.com/article/10.1007/s12079-021-00629-z/fulltext.html

  • 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

    　More details

    Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    DOI： 10.1002/jcp.30348

    researchmap

    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jcp.30348

  • 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

    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

    　More details

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

    DOI： 10.1007/s12079-020-00600-4

    researchmap

    Other Link： http://link.springer.com/article/10.1007/s12079-020-00600-4/fulltext.html

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

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

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

    　More details

    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.job.2020.07.001

    researchmap

  • Retrotransposons Manipulating Mammalian Skeletal Development in Chondrocytes. Reviewed International journal

    Satoshi Kubota, Takanori Ishikawa, Kazumi Kawata, Takako Hattori, Takashi Nishida

    International journal of molecular sciences   21 ( 5 )   2020.2

    　More details

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

    Retrotransposons are genetic elements that copy and paste themselves in the host genome through transcription, reverse-transcription, and integration processes. Along with their proliferation in the genome, retrotransposons inevitably modify host genes around the integration sites, and occasionally create novel genes. Even now, a number of retrotransposons are still actively editing our genomes. As such, their profound role in the evolution of mammalian genomes is obvious; thus, their contribution to mammalian skeletal evolution and development is also unquestionable. In mammals, most of the skeletal parts are formed and grown through a process entitled endochondral ossification, in which chondrocytes play central roles. In this review, current knowledge on the evolutional, physiological, and pathological roles of retrotransposons in mammalian chondrocyte differentiation and cartilage development is summarized. The possible biological impact of these mobile genetic elements in the future is also discussed.

    DOI： 10.3390/ijms21051564

    PubMed

    researchmap

  • Regulatory Roles of HSP90-Rich Extracellular Vesicles

    Takanori Eguchi, Kisho Ono, Kazumi Kawata, Kuniaki Okamoto, Stuart K. Calderwood

    Heat Shock Proteins   3 - 17   2019

    　More details

    Publishing type：Part of collection (book)   Publisher：Springer International Publishing  

    DOI： 10.1007/978-3-030-23158-3_1

    researchmap

  • 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

    　More details

    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

    The platelet-derived growth factor receptor-like (PDGFRL) gene is regarded as a tumor suppressor gene. However, nothing is known about the molecular function of PDGFRL. In this study, we initially clarified its function in chondrocytes. Among all cell lines examined, the PDGFRL mRNA level was the highest in chondrocytic HCS-2/8 cells. Interestingly, the proliferation of chondrocytic HCS-2/8 cells was promoted by PDGFRL overexpression, whereas that of the breast cancer-derived MDA-MB-231 cells was inhibited. Of note, in PDGFRL-overexpressing HCS-2/8 cells, the expression of chondrocyte differentiation marker genes, SOX9, ACAN, COL2A1, COL10A1, and ALP, was decreased. Moreover, we confirmed the expression of PDGFRL mRNA in normal cartilage tissue and chondrocytes. Eventually, the expression of PDGFRL mRNA in condrocytes except in the case of hypertrophic chondrocytes was demonstrated in vivo and in vitro. These findings suggest that PDGFRL plays the different roles, depending upon cell types. Particularly, in chondrocytes, PDGFRL may play a new and important role which is distinct from the function previously reported. J. Cell. Biochem. 118: 4033-4044, 2017. (c) 2017 Wiley Periodicals, Inc.

    DOI： 10.1002/jcb.26059

    Web of Science

    PubMed

    researchmap

  • CCN2 as a Novel Molecule Supporting Energy Metabolism of Chondrocytes Reviewed

    Aya Maeda-Uematsu, Satoshi Kubota, Harumi Kawaki, Kazumi Kawata, Yoshiaki Miyake, Takako Hattori, Takashi Nishida, Norifumi Moritani, Karen M. Lyons, Seiji Iida, Masaharu Takigawa

    JOURNAL OF CELLULAR BIOCHEMISTRY   115 ( 5 )   854 - 865   2014.5

    　More details

    Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

    CCN2/connective tissue growth factor (CTGF) is a unique molecule that promotes both chondrocytic differentiation and proliferation through its matricellular interaction with a number of extracellular biomolecules. This apparently contradictory functional property of CCN2 suggests its certain role in basic cellular activities such as energy metabolism, which is required for both proliferation and differentiation. Comparative metabolomic analysis of costal chondrocytes isolated from wild-type and Ccn2-null mice revealed overall impaired metabolism in the latter. Among the numerous metabolites analyzed, stable reduction in the intracellular level of ATP, GTP, CTP, or UTP was observed, indicating a profound role of CCN2 in energy metabolism. Particularly, the cellular level of ATP was decreased by more than 50% in the Ccn2-null chondrocytes. The addition of recombinant CCN2 (rCCN2) to cultured Ccn2-null chondrocytes partly redeemed the cellular ATP level attenuated by Ccn2 deletion. Next, in order to investigate the mechanistic background that mediates the reduction in ATP level in these Ccn2-null chondrocytes, we performed transcriptome analysis. As a result, several metabolism-associated genes were found to have been up-regulated or down-regulated in the mutant mice. Up-regulation of a number of ribosomal protein genes was observed upon Ccn2 deletion, whereas a few genes required for aerobic and anaerobic ATP production were down-regulated in the Ccn2-null chondrocytes. Among such genes, reduction in the expression of the enolase 1 gene was of particular note. These findings uncover a novel functional role of CCN2 as a metabolic supporter in the growth-plate chondrocytes, which is required for skeletogenesis in mammals. J. Cell. Biochem. 115: 854-865, 2014. (c) 2013 Wiley Periodicals, Inc.

    DOI： 10.1002/jcb.24728

    Web of Science

    PubMed

    researchmap

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

    Kumi Sumiyoshi, Satoshi Kubota, Toshihiro Ohgawara, Kazumi Kawata, Tarek Abd El Kader, Takashi Nishida, Nao Ikeda, Tsuyoshi Shimo, Takashi Yamashiro, Masaharu Takigawa

    Journal of cellular biochemistry   114 ( 9 )   2094 - 100   2013.9

    　More details

    Language：English  

    Micro RNA (miRNA) is a small non-coding post-transcriptional RNA regulator that is involved in a variety of biological events. In order to specify the role of miRNAs in cartilage metabolism, we comparatively analyzed the expression profile of known miRNAs in chicken sternum chondrocytes representing early and late differentiation stages. Interestingly, none of the miRNAs displaying strong expression levels showed remarkable changes along with differentiation, suggesting their roles in maintaining the homeostasis rather than cytodifferentiation of chondrocytes. Among these miRNAs, miR-181a, which is known to play critical roles in a number of tissues, was selected and was further characterized. Human microarray analysis revealed remarkably stronger expression of miR-181a in human HCS-2/8 cells, which strongly maintained a chondrocytic phenotype, than in HeLa cells, indicating its significant role in chondrocytes. Indeed, subsequent investigation indicated that miR-181a repressed the expression of two genes involved in cartilage development. One was CCN family member 1 (CCN1), which promotes chondrogenesis; and the other, the gene encoding the core protein of aggrecan, a major cartilaginous proteoglycan, aggrecan. Based on these findings, negative feedback system via miR-181a to conserve the integrity of the cartilaginous phenotype may be proposed.

    DOI： 10.1002/jcb.24556

    PubMed

    researchmap

  • Role of LRP1 in transport of CCN2 protein in chondrocytes Reviewed

    Kazumi Kawata, Satoshi Kubota, Takanori Eguchi, Eriko Aoyama, Norifumi H. Moritani, Seiji Kondo, Takashi Nishida, Masaharu Takigawa

    JOURNAL OF CELL SCIENCE   125 ( 12 )   2965 - 2972   2012.6

    　More details

    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：COMPANY OF BIOLOGISTS LTD  

    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-beta-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.

    DOI： 10.1242/jcs.101956

    Web of Science

    PubMed

    researchmap

  • 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

    　More details

  • 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

    　More details

    Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Anterior cruciate ligament (ACL)-to-bone interface serves to minimize the stress concentrations that would arise between two different tissues. Mechanical stretch plays an important role in maintaining cell-specific features by inducing CCN family 2/connective tissue growth factor (CCN2/CTGF). We previously reported that cyclic tensile strain (CTS) stimulates alpha 1(I) collagen (COL1A1) expression in human ACL-derived cells. However, the biological function and stress-related response of CCN2/CTGF were still unclear in ACL fibroblasts. In the present study, CCN2/CTGF was observed in ACL-to-bone interface, but was not in the midsubstance region by immunohistochemical analyses. CTS treatments induced higher increase of CCN2/CTGF expression and secretion in interface cells compared with midsubstance cells. COL1A1 expression was not influenced by CCN2/CTGF treatment in interface cells despite CCN2/CTGF stimulated COL1A1 expression in midsubstance cells. However, CCN2/CTGF stimulated the proliferation of interface cells. Our results suggest that distinct biological function of stretch-induced CCN2/CTGF might regulate region-specific phenotypes of ACL-derived cells. (C) 2011 Elsevier Inc. All rights reserved.

    DOI： 10.1016/j.bbrc.2011.04.138

    Web of Science

    PubMed

    researchmap

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

    Kumi Sumiyoshi, Satoshi Kubota, Toshihiro Ohgawara, Kazumi Kawata, Takashi Nishida, Tsuyoshi Shimo, Takashi Yamashiro, Masaharu Takigawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   402 ( 2 )   286 - 290   2010.11

    　More details

    Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

    The process of endochondral ossification is strictly regulated by a variety of extracellular and intracellular factors. Recently, it has become recognized that specific miRNAs are involved in this process by regulating the expression of the relevant genes at the post-transcriptional level. In this present study we obtained the first evidence of the involvement of a specific micro RNA (miRNA) in the regulation of the chondrocyte phenotype during late stages of differentiation. By use of the microarray technique, miR-1 was identified as this miRNA, the expression of which was most repressed upon hypertrophic differentiation. Transfection of human chondrocytic HCS-2/8 cells and chicken normal chondrocytes with miR-1 led to repressed expression of aggrecan, the major cartilaginous proteoglycan gene. Therefore, miR-1 was found to be involved in the regulation of the chondrocytic phenotype and thus to play an important role in chondrocytes during the late stage of the differentiation process, maintaining the integrity of the cartilage tissue. (C) 2010 Elsevier Inc. All rights reserved.

    DOI： 10.1016/j.bbrc.2010.10.016

    Web of Science

    PubMed

    researchmap

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

    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

    　More details

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

    CCN2 plays a central role in the development and growth of mesenchymal tissue and promotes the regeneration of bone and cartilage in vivo. Of note, abundant CCN2 is contained in platelets, which is thought to play an important role in the tissue regeneration process. In this study, we initially pursued the possible origin of the CCN2 in platelets. First, we examined if the CCN2 in platelets was produced by megakaryocyte progenitors during differentiation. Unexpectedly, neither megakaryocytic CMK cells nor megakaryocytes that had differentiated from human haemopoietic stem cells in culture showed any detectable CCN2 gene expression or protein production. Together with the fact that no appreciable CCN2 was detected in megakaryocytes in vivo, these results suggest that megakaryocytes themselves do not produce CCN2. Next, we suspected that mesenchymal cells situated around megakaryocytes in the bone marrow were stimulated by the latter to produce CCN2, which was then taken up by platelets. To evaluate this hypothesis, we cultured human chondrocytic HCS-2/8 cells with medium conditioned by differentiating megakaryocyte cultures, and then monitored the production of CCN2 by the cells. As suspected, CCN2 production by HCS-2/8 was significantly enhanced by the conditioned medium. We further confirmed that human platelets were able to absorb/uptake exogenous CCN2 in vitro. These findings indicate that megakaryocytes secrete some unknown soluble factor(s) during differentiation, which factor stimulates the mesenchymal cells to produce CCN2 for uptake by the platelets. We also consider that, during bone growth, such thrombopoietic-mesenchymal interaction may contribute to the hypertrophic chondrocyte-specific accumulation of CCN2 that conducts endochondral ossification.

    DOI： 10.1007/s12079-009-0067-1

    Web of Science

    PubMed

    researchmap

  • 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

    　More details

    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-LISS  

    The low-density lipoprotein receptor-related protein 1 (LRP1) is known as an endocytic and signal transmission receptor. We formerly reported the gene expression and the localization of LRP1 in cartilage tissue and chondrocytes, but its roles in the differentiation of chondrocytes remained to be investigated. Here, in order to address this issue, we employed RNAi strategy to knockdown Irpl in chondrocytic cells and obtained findings indicating a critical role therein. As a result of IrpI knockdown, aggrecan and col2a1 mRNA levels were decreased. However, that of col10a1 or mmp13 mRNA was rather increased. Under this condition, we performed a promoter assay for Axing, which is known to be induced by activation of the WNT/beta-catenin (beta cat) signaling pathway. Thereby, we found that Axing promoter activity was enhanced in the Irpl knockdown cells. Furthermore, when the WNT/beta-catenin pathway was activated in chondrocytic cells by WNT3a or SB216763, which inhibits the phosphorylation of GSK3 beta, the mRNA levels of aggrecan and col2a1 were decreased, whereas that of mmp13 was increased. Additionally, the level of phosphorylated protein kinase C (PKC) zeta was also decreased in the Irp1 knockdown cells. When the phosphorylation of PKC zeta was selectively inhibited, aggrecan and col2a1 mRNA levels decreased, whereas the mmp13 mRNA level increased. These data demonstrate that LRP1 exerts remarkable effects to retain the mature phenotype of chondrocytes as a critical mediator of cell signaling. Our findings also indicate that the onset of hypertrophy during endochondral ossification appears to be particularly dependent on the WNT and PKC signaling initiated by LRP1. J. Cell. Physiol. 222: 138-148, 2010. (C) 2009 Wiley-Liss, Inc.

    DOI： 10.1002/jcp.21930

    Web of Science

    PubMed

    researchmap

  • 学生のリアルタイム評価を応用した授業内容改善FDシステムの開発 Reviewed

    原哲也, 児玉(島津)千恵, 河田かずみ, 白嶋章, 皆木省吾

    日本歯科医学教育学会雑誌   26 ( 1 )   2010

    　More details

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

    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

    　More details

    Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

    EphA4 receptor tyrosine kinase has been shown to be critically involved in neural tissue development. Here, we found EphA4 was also distributed among hypertrophic chondrocytes and osteoblasts in the growth plate of developing mouse long bones. In vitro evaluation revealed that ephA4 expression was elevated Upon hypertrophic differentiation of chondrocytes and that markedly stronger expression was observed in osteoblastic SaOS-2 than chondrocytic HCS-2/8 cells. Of note, RNAi-mediated silencing of ephA4 in SaOS-2 cells resulted in the repression of osteocalcin gene expression and alkaline phosphatase activity. Interestingly, confocal laser-scanning Microscopic analysis revealed the presence of EphA4 molecules in the nucleus as well as on the surface of SaOS-2 cells. These findings are the first indication of a critical role of EphA4 in ossification, especially at the final stage in which osteoblasts and hypertrophic chondrocytes play major roles. (C) 2008 Elsevier Inc. All rights reserved.

    DOI： 10.1016/j.bbrc.2008.06.089

    Web of Science

    researchmap

  • Promotion of bone regeneration by CCN2 incorporated into gelatin hydrogel Reviewed

    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

    　More details

    Language：English   Publishing type：Research paper (scientific journal)   Publisher：MARY ANN LIEBERT, INC  

    CCN family protein 2/connective tissue growth factor (CCN2/CTGF) is a unique molecule that promotes the entire endochondral ossification process and regeneration of damaged articular cartilage. Also, CCN2 has been shown to enhance the adhesion and migration of bone marrow stromal cells as well as the growth and differentiation of osteoblasts; hence, its utility in bone regeneration has been suggested. Here, we evaluated the effect of CCN2 on the regeneration of an intractable bone defect in a rat model. First, we prepared two recombinant CCN2s of different origins, and the one showing the stronger effect on osteoblasts in vitro was selected for further evaluation, based on the result of an in vitro bioassay. Next, to obtain a sustained effect, the recombinant CCN2 was incorporated into gelatin hydrogel that enabled the gradual release of the factor. Evaluation in vivo indicated that CCN2 continued to be released at least for up to 14 days after its incorporation. Application of the gelatin hydrogel-CCN2 complex, together with a collagen scaffold to the bone defect prepared in a rat femur resulted in remarkable induction of osteoblastic mineralization markers within 2 weeks. Finally, distinct enhancement of bone regeneration was observed 3 weeks after the application of the complex. These results confirm the utility of CCN2 in the regeneration of intractable bone defects in vivo when the factor is incorporated into gelatin hydrogel.

    DOI： 10.1089/ten.tea.2007.0167

    Web of Science

    PubMed

    researchmap

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

    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

    　More details

    Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC MICROBIOLOGY  

    Matrix metalloproteinase 3 (MMP3) is well known as a secretory endopeptidase that degrades extracellular matrices. Recent reports indicated the presence of MMPs in the nucleus (A. J. Kwon et al., FASEB J. 18:690-692, 2004); however, its function has not been well investigated. Here, we report a novel function of human nuclear MMP3 as a trans regulator of connective tissue growth factor (CCN2/CTGF). Initially, we cloned MMP3 cDNA as a DNA-binding factor for the CCN2/CTGF gene. An interaction between MMP3 and transcription enhancer dominant in chondrocytes (TRENDIC) in the CCN2/CTGF promoter was confirmed by a gel shift assay and chromatin immunoprecipitation. The CCN2/CTGF promoter was activated by overexpressed MMP3, whereas a TRENDIC mutant promoter lost the response. Also, the knocking down of MMP3 suppressed CCN2/CTGF expression. By cytochemical and histochemical analyses, MMP3 was detected in the nuclei of chondrocytic cells in culture and also in the nuclei of normal and osteoarthritic chondrocytes in vivo. The nuclear translocation of externally added recombinant MMP3 and six putative nuclear localization signals in MMP3 also were shown. Furthermore, we determined that heterochromatin protein gamma coordinately regulates CCN2/CTGF by interacting with MMP3. The involvement of this novel role of MMP3 in the development, tissue remodeling, and pathology of arthritic diseases through CCN2/CTGF regulation thus is suggested.

    DOI： 10.1128/MCB.01288-07

    Web of Science

    researchmap

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

    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

    　More details

    Language：English   Publishing type：Research paper (scientific journal)   Publisher：HISTOCHEMICAL SOC INC  

    CCN2/connective tissue growth factor (CCN2/CTGF) is a critical signaling modulator of mesenchymal tissue development. This study investigated the localization and expression of CCN2/CTGF as a factor supporting angiogenesis and chondrogenesis during development of secondary ossification centers in the mouse tibial epiphysis. Formation of the secondary ossification center was initiated by cartilage canal formation and blood vessel invasion at 7 days of age, and onset of ossification was observed at 14 days. In situ hybridization showed that CCN2/CTGF mRNA was distinctively expressed in the region of the cartilage canal and capsule-attached marginal tissues at 7 days of age, and distinct expression was also observed in proliferating chondrocytes around the marrow space at 14 days of age. Immunostaining showed that CCN2/CTGF was distributed broadly around the expressed cells located in the central region of the epiphysis, where the chondrocytes become hypertrophic and the cartilage canal enters into the hypertrophic mass. Furthermore, an overlapping distribution of metal loproteinase (MMP)9 and CCN2/CTGF was found in the secondary ossification center. These findings suggest that the CCN2/CTGF is involved in establishing epiphyseal vascularization and remodeling, which eventually determines the secondary ossification center in the developing epiphysial cartilage.

    DOI： 10.1369/jhc.7A7263.2007

    Web of Science

    researchmap

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

    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

    　More details

    Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

    CCN4/Wnt-induced secreted protein 1 (WISP1) is one of the CCN (CTGF/Cyr61/Nov) family proteins. CCN members have typical structures composed of four conserved cysteine-rich modules and their variants lacking certain modules, generated by alternative splicing or gene mutations, have been described in various pathological conditions. Several previous reports described a CCN4/WISP1 variant (WISP1v) lacking the second module in a few malignancies, but no information concerning the production of WISP1 variants in normal tissue is currently available. The expression of CCN4/WISP1 mRNA and its variants were analyzed in a human chondrosarcoma-derived chondrocytic cell line, HCS-2/8, and primary rabbit growth cartilage (RGC) chondrocytes. First, we found WISP1v and a novel variant of WISP1 (WISP1vx) to be expressed in HCS-2/8, as well as full-length WISP1 mRNA. This new variant was lacking the coding regions for the second and third modules and a small part of the first module. To monitor the expression of CCN4/WISP1 mRNA along chondrocyte differentiation, RGC cells were cultured and sampled until they were mineralized. As a result, we identified a WISP1v ortholog in normal RGC cells. Interestingly, the WISP1v mRNA level increased dramatically along with terminal differentiation. Furthermore, overexpression of WISP1v provoked expression of an alkaline phosphatase gene that is a marker of terminal differentiation in HCS-2/8 cells. These findings indicate that WISP1v thus plays a critical role in chondrocyte differentiation toward endochondral ossification, whereas HCS-2/8-specific WISP1vx may be associated with the transformed phenotypes of chondrosarcomas.

    DOI： 10.1111/j.1742-4658.2007.05709.x

    Web of Science

    researchmap

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

    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

    　More details

    Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER  

    Connective tissue growth factor (CTGF/CCN2) plays a critical role in endochondral bone formation; however, CCN2 also promotes angiogenesis and bone metastasis in breast cancer. Chondrocytic HCS-2/8 cells and breast cancer MDA231 cells produce over 6 times more CCN2 than any other cell type. In this study, we demonstrate that these cell lines employ different transcriptional strategies for ccn2 gene induction. Four tandem copies of the dominant transcriptional enhancer in chondrocytes (4 x TRENDIC) were chimerically connected to an SV40 pro-moter-luciferase construct and subsequently analyzed. The enhancement of the promoter activity by 4 x TRENDIC was greater in the HCS-2/8 cells (7-fold) than in the other 4 cell lines (3-4 fold). The TRENDIC-binding protein complex was detected at a higher signal in the HCS-2/8 cells than in the other cell lines. In addition, the HCS-2/8 nuclear factors strongly targeted not only TRENDIC, but also the previously reported basal control element and a novel enhancer element in the ccn2 promoter. In contrast, high-level ccn2 gene induction in MDA231 cells was largely dependent on Smad signaling through the Smad-binding element in the ccn2 promoter. Based on these results, we propose a model of differential transcription of the ccn2 gene between the chondrocytic cell line and the breast cancer cell line, and therefore imply that these cells utilize distinct transcriptional strategies to obtain the enhanced CCN2 production that is not observed in other types of cells. (c) 2007 Elsevier Masson SAS. All rights reserved.

    DOI： 10.1016/j.biochi.2006.12.006

    Web of Science

    researchmap

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

    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

    　More details

    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Low density lipoprotein receptor (LDLR)-related protein 1 (LRP1/CD91) is one of the receptors of CCN2 that conducts endochondral ossification and cartilage repair. LRP1 is a well-known endocytic receptor, but its distribution among chondrocytes remains to be elucidated. We herein demonstrate for the first time that the distribution of LRP1 in chondrocytes except for hypertrophic chondrocytes in vivo and in vitro. Interestingly, the LRP1 levels were higher in mature chondrocytic HCS-2/8 and osteoblastic SaOS-2 than in other cells, whereas the other LDLR family members involved in ossification were detected at lower levels in HCS-2/8. It was interesting to note that in HCS-2/8, LRP1 was observed not only on the cell surface and in the cytoplasm, but also in the nucleus. Exogenously added CCN2 was incorporated into HCS-2/8, which was partially co-localized with LRP1, and targeted to the recycling endosomes and nucleus as well as the lysosomes. These findings suggest specific roles of LRP1 in cartilage biology. (c) 2006 Elsevier Inc. All rights reserved.

    DOI： 10.1016/j.bbrc.2006.04.109

    Web of Science

    researchmap

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

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

    FEBS LETTERS   579 ( 17 )   3751 - 3758   2005.7

    　More details

    Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

    The cis-acting element of structure-anchored repression (CAESAR) is a post-transcriptional regulatory element of gene expression, which is located in the 3'-untranslated region (UTR) of the human ccn2 gene (ctgflccn2). In this report, the repression mechanism of CAESAR, as well as the structural requirement, was investigated. Removal of minor stem-loops from CAESAR resulted in proportional attenuation of the repressive function, whereas removal of the single bulge or modification of primary nucleotide sequence did not affect its functionality. In light of functional mechanism, CAESAR exerted no significant effects on stability or nuclear export of the cis-linked mRNA. However, this element significantly interfered with the association of such mRNA on ribosome and slowed down the translation process thereafter in vitro. A translation repression mechanism by RNA secondary structure to determine the basal ctgflccn2 expression level was uncovered herein. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

    DOI： 10.1016/j.febslet.2005.05.068

    Web of Science

    researchmap

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

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

    JOURNAL OF BIOCHEMISTRY   136 ( 3 )   279 - 282   2004.9

    　More details

    Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE BIOCHEMICAL SOC  

    Wound healing and tissue regeneration are usually initiated by coagulation followed by fibrous tissue formation. In the present study, we discovered an abundance of connective tissue growth factor (CTGF/CCN2) in human platelets, which was released along with the coagulation process. The CTGF/CCN2 content in platelets was 10-fold higher than that in arterial tissue. Furthermore, the CTGF/CCN2 content in a single platelet was computed to be more than 20-fold higher than that of any other growth factor reported. Considering that CTGF/CCN2 promotes angiogenesis, cartilage regeneration, fibrosis and platelet adhesion, it may be now regarded as one of the major functional components of platelets.

    DOI： 10.1093/jb/mvh126

    Web of Science

    researchmap

▼display all

Books

  • Gene Expression Analysis of CCNs Along with Odontoblastic Differentiation In Vivo

    Springer  2023 

    　More details

  • Regulatory Roles Of HSP90-rich Extracellular Vesicles. in Heat Shock Protein 90 in Human Diseases and Disorders

    Eguchi T, Ono K, Kazumi Kawata K, Okamoto K, Calderwood SK

    Springer Nature Switzerland AG  2019 

    　More details

  • Analysis of transcytosis of CCN2 by chondrocytes. in Methods in Molecular Biology: CCN Proteins: Methods and Protocols

    Kawata K, Kubota S, Takigawa M

    Springer  2016 

    　More details

MISC

  • 骨・軟骨組織における一次繊毛

    河田かずみ

    腎と透析   87 ( 5 )   2019.11

    　More details

    Authorship：Lead author  

    researchmap

  • マルチに働く硬組織の一次繊毛ー一次繊毛は細胞を並べている？

    河田かずみ

    実験医学   2018

    　More details

    Authorship：Lead author  

    researchmap

  • CCN2/CTGFのシグナル/トランスサイトーシス受容体としてのLRP1

    河田かずみ, 久保田聡, 滝川正春

    生体の科学   2013

    　More details

    Authorship：Lead author  

    researchmap

Presentations

  • 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  2024.2.16 

    　More details

    Event date： 2024.2.16 - 2024.2.17

    researchmap

  • 軟骨細胞分化におけるPPARｇの機能の解明への挑戦

    畚野里紗, 河田かずみ, 滝川正春, 上岡寛, 久保田聡

    第44回岡山歯学会総会・学術集会  2023.12.10 

    　More details

    Event date： 2023.12.10

    researchmap

  • Intraflagellar transport protein 88によるHippo経路を介した象牙芽前駆細胞増殖制御機構

    河田 かずみ, 青山 絵理子, 滝川 正春, 久保田 聡

    第46回日本分子生物学会年会  2023.12.7 

    　More details

    Event date： 2023.12.6 - 2023.12.8

    Language：English   Presentation type：Symposium, workshop panel (public)  

    researchmap

  • 軟⾻細胞におけるCCN2由来circRNAの発現とその⽣成メカニズム‧機能 の考察

    加藤 壮真, 河田 かずみ, 田 崇, 滝川 正春, 飯田 征二, 久保田 聡

    第46回日本分子生物学会年会  2023.12.6 

    　More details

    Event date： 2023.12.6 - 2023.12.8

    Language：English   Presentation type：Symposium, workshop panel (public)  

    researchmap

  • 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回歯科基礎医学会学術大会  2023.9.18 

    　More details

    Event date： 2023.9.16 - 2023.9.18

    researchmap

  • 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

    第65回歯科基礎医学会学術大会  2023.9 

    　More details

    Event date： 2023.9.16 - 2023.9.18

    researchmap

  • 軟骨細胞における CCN2 由来環状 RNA 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 

    　More details

    Event date： 2023.9.2

    researchmap

  • 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 

    　More details

    Event date： 2023.9.2

    researchmap

  • 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、滝川正春、飯田征二、久保田聡

    第41回日本骨代謝学会学術集会  2023.7.28 

    　More details

    Event date： 2023.7.27 - 2023.7.29

    researchmap

  • 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回日本骨代謝学会学術集会  2023.7.28 

    　More details

    Event date： 2023.7.27 - 2023.7.29

    researchmap

  • 軟骨細胞におけるCCN2由来環状RNAの探索とその機能

    加藤壮真, 河田かずみ, 水川朋美, 西田 崇, 久保田聡

    第35回日本軟骨代謝学会  2023.3.4 

    　More details

    Event date： 2023.3.3 - 2023.3.4

    researchmap

  • 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, 水川朋美, 久保田聡

    第64回歯科基礎医学会学術大会  2022.9.19 

    　More details

    Event date： 2022.9.17 - 2022.9.19

    researchmap

  • Intraflagellar 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回歯科基礎医学会学術大会  2022.9.18 

    　More details

    Event date： 2022.9.17 - 2022.9.19

    researchmap

  • 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 

    　More details

    Event date： 2022.9.3

    researchmap

  • 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 

    　More details

    Event date： 2022.2.18 - 2022.2.19

    researchmap

  • 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  2021.12.2 

    　More details

    Event date： 2021.12.1 - 2021.12.3

    researchmap

  • 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 

    　More details

    Event date： 2021.11.3 - 2021.11.5

    researchmap

  • 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

    第39回日本骨代謝学会学術集会  2021.10 

    　More details

    Event date： 2021.10

    researchmap

  • 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 

    　More details

    Event date： 2021.9

    researchmap

  • 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 

    　More details

    Event date： 2021.9

    researchmap

  • CCN2、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 

    　More details

    Event date： 2021.9

    researchmap

  • 象牙芽前駆細胞において一次繊毛は古典的WNTシグナルと相互作用しながら細胞分化を制御する

    河田かずみ, 成田啓之, 鷲尾絢子, 北村知昭, 西原達次, 久保田聡, 竹田扇

    第93回日本生化学会大会  2020.9 

    　More details

    Event date： 2020.9

    researchmap

  • CCN2、CCN3による軟骨細胞増殖と分化の制御を抑制する癌抑制遺伝子PDGFRL

    河田 かずみ, 久保田 聡, 滝川 正春

    第40回岡山歯学会総会・学術大会  2019.12 

    　More details

    Event date： 2019.12

    researchmap

  • Essential role of CCN2 that supports the basal energy metabolism in chondrocytes

    2013.9 

    　More details

    Event date： 2013.9.11 - 2013.9.13

    researchmap

  • 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 (Web)  2013.9 

    　More details

    Event date： 2013

    Language：Japanese  

    researchmap

  • 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  2012.12  AMER SOC CELL BIOLOGY

    　More details

    Event date： 2012

    Language：English  

    researchmap

  • 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  2007.9  AMER SOC BONE & MINERAL RES

    　More details

    Event date： 2007.9

    Language：English  

    researchmap

  • 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 

    　More details

  • 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 

    　More details

  • Long noncoding RNAs that regulate CCN2.

    Kubota S, Ishikawa T, Mizukawa T, Kondo S, El-Seoudi A, Nishida T, Hattori T, Kawata K, Furumatsu T, Takarada T, Ono M, Takigawa M

    The 10th International Workshop of CCN Family of Genes  2019.10 

    　More details

  • 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 

    　More details

  • 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 

    　More details

  • 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 岡山歯学会総会・学術集会  2017 

    　More details

  • 骨形成における低密度リポタンパク質受容体関連タンパク質1 (LRP1)の役割

    第30回日本軟骨代謝学会  2017 

    　More details

  • 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

    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 

    　More details

  • 軟骨細胞分化における癌抑制遺伝子PDGRTL-like (PDGFRL)の役割

    第29回日本軟骨代謝学会  2016 

    　More details

  • 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 

    　More details

  • Intraflagellar transport protein 88 (IFT88) は細胞分裂期においても繊毛形成に働く

    第 120回日本解剖学会総会・全国学術集会・第 92回日本生理学会大会  2015 

    　More details

  • Canonical Wnt signaling pathway regulates not only the odontobast differentiation through primary cilia but also formation of primary cilia

    2014 ascb/ifcb meeting  2014.12 

    　More details

  • 細胞分裂期の象牙芽細胞におけるIFT88の役割

    第56回歯科基礎医学会学術大会・総会  2014.9 

    　More details

  • 古典的WNTシグナル下流遺伝子Ccn6/Wisp3による一次繊毛形成調節機構の可能性

    第6回日本CCNファミリー研究会  2014.8 

    　More details

  • 象牙芽細胞分化制御における一次繊毛と古典的WNTシグナルの相互作用

    第32回日本骨代謝学会学術集会  2014.7 

    　More details

  • 象牙芽細胞分化における一次繊毛の機能

    第5回繊毛研究会  2014.5 

    　More details

  • 象牙芽細胞における古典的WNTシグナルの生理機能の解析

    第119回日本解剖学会総会・全国学術集会  2014.3 

    　More details

  • 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, 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, Karen M Lyons, 飯田征二, 滝川正春

    第27回日本軟骨代謝学会  2014.2 

    　More details

  • Primary cilia regulate the differentiation of odontoblasts

    Takeda S, Kawata, K, Narita K

    2013 ascb annual meeting  2013.12 

    　More details

  • 象牙芽細胞における一次繊毛を介したWNTシグナルの生理機能の解析

    河田かずみ, 成田啓之, 竹田扇

    第73回日本解剖学会中部支部学術集会  2013.10 

    　More details

  • New functional aspects of known molecules as CCN2 partners.

    Kubota S, Kawata K, Aoyama E, Takigawa M

    Seventh Internal Workshop on the CCN Family of Genes  2013.10 

    　More details

  • A novel pathway of hedgehog signaling modification by primary cilia in odontoblasts

    Kawata K, Narita K, Takeda S

    ANZBMS 23rd Annual Scientific meeting  2013.9 

    　More details

  • 象牙芽細胞のIft88はアクチンダイナミクスを介して細胞運動を制御する

    河田かずみ, 成田啓之, 鷲尾絢子, 北村知昭, 西原達次, 竹田扇

    第4回繊毛研究会  2013.9 

    　More details

  • 象牙芽細胞における一次繊毛形成遺伝子 IFT88 の生理機能の解析

    河田かずみ, 竹田扇

    第55回歯科基礎医学会学術大会・総会  2013.9 

    　More details

  • Crucial Roles Of CCN2 In Energy Metabolism In Chondrocytes

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

    2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Research  2013.5 

    　More details

  • 象牙芽細胞の一次繊毛を介したhedgehogシグナルの新規修飾機能

    河田かずみ, 成田啓之, 竹田扇

    国際骨代謝学会・日本骨代謝学会 第２回合同国際会議  2013.5 

    　More details

  • 軟骨細胞のエネルギー代謝を支えるCCN2/CTGF

    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, Karen M. Lyons, 飯田征二, 滝川正春

    第26回日本軟骨代謝学会  2013.3 

    　More details

  • 象牙芽細胞における一次繊毛の生理機能の解析

    河田かずみ, 竹田扇

    第118回日本解剖学会総会・全国学術集会  2013.3 

    　More details

  • 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

    河田かずみ, 久保田聡, 服部高子, 青山絵理子, ジャヌネ ダニーロ, 滝川正春

    第85回日本生化学会大会  2012.12 

    　More details

  • 軟骨細胞のエネルギー代謝におけるCCN2/CTGFの役割

    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, Karen M. Lyons, 飯田征二, 滝川正春

    第35回日本分子生物学会年会  2012.12 

    　More details

  • 軟骨細胞の基本代謝におけるCCN2の役割

    前田彩, 久保田聡, 三宅由晃, 河田かずみ, 森谷徳文, 滝川正春

    第30回日本骨代謝学会学術集会  2012.7 

    　More details

  • 癌抑制遺伝子PDGFRLによる軟骨細胞分化制御

    Kawata K, Kubota S, Eguchi T, Aoyama E, Moritani NH, Oka M, Kawaki H, Takigawa M

    第30回日本骨代謝学会学術集会  2012.7 

    　More details

  • The low-density lipoprotein receptor related protein 1 (LRP1) deficiency in the cartilage tissue leads to skeletal dysmorphism

    Kawata K, Kubota S, Hattori T, Aoyama E, Janune D, Takigawa M

    第34回日本分子生物学会年会  2011.12 

    　More details

  • Role of the low-density lipoprotein receptor-related protein-1 in regulation of chondrocyte differentiation.

    Kawata K, Kubota S, Eguchi T, Moritani NH, Shimo T, Kondo S, Nishida T, Minagi S, Takigawa M

    第32回岡山歯学会総会・学術集会  2011.11 

    　More details

  • ROLE OF THE LOW-DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 1 (LRP1) IN CCN2 PROTEIN TRANSPORTATION IN CHONDROCYTES

    Kawata K, Kubota S, Eguchi T, Aoyama E, Kondo S, Hattori T, Takigawa M

    Cell Signaling Networks 2011  2011.10 

    　More details

  • Expression of platelet-derived growth factor receptor-like (PDGFRL) gene in chondrocytes

    Kawata K, Kubota S, Eguchi T, Aoyama E, Moritani NH, Oka M, Kawaki H, Takigawa M

    第84回日本生化学会大会  2011.9 

    　More details

  • ヒト前十字靱帯細胞におけるCCN2/CTGFの機能と周期的伸張刺激負荷の効果

    三宅由晃, 古松毅之, 久保田聡, 河田かずみ, 尾崎敏文, 滝川正春

    日本CCNファミリー研究会第４回学術集会  2011.8 

    　More details

  • Role of the low-density lipoprotein receptor related protein 1 (LRP1) in CCN2 protein transportation in chondrocytes

    Kawata K, Kubota S, Eguchi T, Aoyama E, Kondo S, Hattori T, Takigawa M

    日本CCNファミリー研究会第４回学術集会  2011.8 

    　More details

  • 3’UTRを介したCCN1(Cyr61)遺伝子発現調節機構の解明

    住吉久美, 久保田聡, 仲川洋介, 湊雅直, 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CCNファミリー研究会第４回学術集会  2011.8 

    　More details

  • 前十字靱帯細胞におけるCCN2/CTGFの機能と周期的伸張刺激負荷の効果

    三宅由晃, 古松毅之, 久保田聡, 河田かずみ, 尾崎敏文, 滝川正春

    第29回日本骨代謝学会学術集会  2011.7 

    　More details

  • 前十字靱帯細胞におけるCCN2/CTGFの機能と周期的伸張刺激負荷の効果

    三宅由晃, 古松毅之, 久保田聡, 河田かずみ, 尾崎敏文, 滝川正春

    第43回日本結合組織学会学術大会・第58回マトリックス研究会大会合同学術集会  2011.6 

    　More details

  • 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

    第43回日本結合組織学会学術大会・第58回マトリックス研究会大会合同学術集会  2011.6 

    　More details

  • 長期間咬合支持を喪失させたラットにおける咬合支持の回復が空間認知能に及ぼす影響

    坂本隼一, 原哲也, 黒住明正, 岡森彦, 黒田知沙, 河田かずみ, 荒木大介, 飯田祥与, 皆木省吾

    社団法人日本補綴歯科学会第120回記念学術大会  2011.5 

    　More details

  • マイクロRNAによる軟骨細胞形質の制御と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

    第24回日本軟骨代謝学会  2011.3 

    　More details

  • 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

    第33回日本分子生物学会年会・第83回日本生化学会大会合同大会  2010.12 

    　More details

  • Role of the low-densitylipoprotein receptor-related protein 1 (LRP1) in CCN2 protein transportation in chondrocyte

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

    第33回日本分子生物学会年会・第83回日本生化学会大会合同大会  2010.12 

    　More details

  • MULTIPLE REGLUATION OF HUMAN CCN1 VIA THE 3’UTR UNTRANSLATED REGION AND ITS BIOLOGICAL SIGNIFICANCE

    6th International Workishop on the CCN Family of Genes  2010.10 

    　More details

  • ROLE OF THE LOW-DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 1 (LRP1) IN CCN2/CONNECTIVE TISSUE GROWTH FACTOR (CTGF) PROTEIN TRANSPORTATION IN CHONDROCYTE

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

    6th International Workishop on the CCN Family of Genes  2010.10 

    　More details

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

    2010.10 

    　More details

  • 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

    2010.7 

    　More details

  • 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

    第28回日本骨代謝学会学術集会  2010.7 

    　More details

  • 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

    河田かずみ, 久保田聡, 江口傑徳, 青山絵理子, 志茂剛, 森谷徳文, 近藤誠二, 西田崇, 皆木省吾, 滝川正春

    第32回日本分子生物学会年会  2009.12 

    　More details

  • MMP3はクロマチンに局在し、CCNファミリー遺伝子を制御する

    江口傑徳, 河田かずみ, 久保田聡, 萩原真, 小松寿明, 杉浦進介, 中島美砂子, 滝川正春, 松下健二

    第32回日本分子生物学会年会  2009.12 

    　More details

  • Socratec を用いた双方向対話型歯科補綴学教育の評価

    原哲也, 皆木省吾, 坂本隼一, 河田かずみ, 白嶋章

    第28回日本歯科医学教育学会  2009.11 

    　More details

  • 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機能

    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

    第82回日本生化学会大会  2009.10 

    　More details

  • 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

    岡森彦, 久保田聡, 黒田知沙,河田かずみ, 原哲也, 皆木省吾, 滝川正春

    第51回歯科基礎医学会学術大会・総会  2009.9 

    　More details

  • 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

    黒田知沙, 久保田聡, 河田かずみ, 青山絵理子, 住吉久美, 皆木省吾, 滝川正春

    第51回歯科基礎医学会学術大会・総会  2009.9 

    　More details

  • 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機能

    河田かずみ, 久保田聡, 江口傑徳, 青山絵理子, 志茂剛, 森谷徳文, 近藤誠二, 西田崇, 皆木省吾, 滝川正春

    第３回CCN研究会  2009.8 

    　More details

  • 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

    第27回日本骨代謝学会  2009.7 

    　More details

  • アシタバはBMP-2遺伝子の発現を増加させて，卵巣摘出ラットの骨量減少を抑制する

    原哲也, 兒玉千恵, 黒住明正, 河田かずみ, 岡 森彦, 黒田知沙, 皆木省吾

    社団法人日本補綴歯科学会第118回学術大会  2009.6 

    　More details

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

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

    The Second International Symposium of Medical and Dental Education  2009.5 

    　More details

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

    Kuroda C, Kubota S, Kawata K, Aoyama E, Sumiyoshi K, Oka M, Minagi S, Takigawa M

    The Second International Symposium of Medical and Dental Education  2009.5 

    　More details

  • Chondrocyte-haemopoietic cell interaction that inducea CCN2 and its physiological significanc

    Sumiyoshi K, Kubota S, Furuta R, Kawaki H, Aoyama E, Kawata K, Ohgawara T, Yamashiro T, Takigawa M

    The Second International Symposium of Medical and Dental Education  2009.5 

    　More details

  • 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

    住吉久美, 久保田聡, 古田里佳, 青山絵理子, 川木晴美, 河田かずみ, 大河原敏博, 山城隆, 滝川正春

    第22回日本軟骨代謝学会  2009.3 

    　More details

  • 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

    黒田知沙, 久保田聡, 河田かずみ, 皆木省吾, 滝川正春

    第22回日本軟骨代謝学会  2009.3 

    　More details

  • 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, 久保田聡, 河田かずみ, 椋代義樹, 上原淳二, 大河原敏博, 伊原木聰一郎, 佐々木明, 窪木拓男, 滝川正春

    第22回日本軟骨代謝学会  2009.3 

    　More details

  • 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

    黒田知沙, 久保田聡, 河田かずみ, 皆木省吾, 滝川正春

    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  2008.12 

    　More details

  • 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序

    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

    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  2008.12 

    　More details

  • Novel transcriptional regulation of CCN2/CTGF by nuclear translocated MMP

    Eguchi T, Kubota S, Kawata K, Mukudai Y, Uehara J, Ohgawara T, Ibaragi S, Sasaki A, Kuboki T, Takigawa M

    The 5th International Workishop on the CCN Family of Genes  2008.10 

    　More details

  • 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

    岡森彦, 久保田聡, 河田かずみ, 黒田知沙, 皆木省吾, 滝川正春

    第26回日本骨代謝学会学術集会  2008.10 

    　More details

  • 軟骨細胞および骨芽細胞におけるEphA4の発現とその意義

    黒田知沙, 久保田聡, 河田かずみ, 皆木省吾, 滝川正春

    第26回日本骨代謝学会学術集会  2008.10 

    　More details

  • 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

    第26回日本骨代謝学会学術集会  2008.10 

    　More details

  • 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

    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

    第2回日本CCNファミリー研究会  2008.8 

    　More details

  • 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

    黒田知沙, 久保田聡, 河田かずみ, 皆木省吾, 滝川正春

    第2回日本CCNファミリー研究会  2008.8 

    　More details

  • LRP1による軟骨細胞分化の制御：Wntシグナル経路との関連

    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

    第18回中国・四国骨代謝研究会  2008.7 

    　More details

  • 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

    黒田知沙, 久保田聡, 河田かずみ, 青山絵理子, 皆木省吾, 滝川正春

    第18回中国・四国骨代謝研究会  2008.7 

    　More details

  • 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

    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

    第21回日本軟骨代謝学会  2008.3 

    　More details

  • Distribution and gene expression of EphA4 during long bone development

    Kuroda C, Kubota S, Kawata K, Minagi S, Takigawa M

    The 1st International Symposium on Graduate Medical and Dental Education  2008.2 

    　More details

  • Functional analysis of the low densitylipoprotein receptor-related protein (LRP1) in chondrocytes

    Kawata K, Kubota S, Eguchi T, Aoyama E, Minagi S, Takigawa M

    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  2007.12 

    　More details

  • 軟骨細胞においてマトリックスメタロプロテアーゼ-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

    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, 佐々木郎, 窪木拓男, 滝川正春

    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  2007.12 

    　More details

  • Functional analysis of a CCN2/CTGF receptor, the low density lipoprotein receptor-related protein (LRP1), in chondrocytes.

    Kawata K, Kubota S, Eguchi T, Aoyama E, Minagi S, Takigawa M

    第1回日本CCNファミリー研究会  2007.10 

    　More details

  • CCN2の転写調節因子としての働き

    江口傑徳, 久保田聡, 河田かずみ, 上原淳二, 椋代義樹, 大河原敏博, 伊原木聰一郎, 佐々木朗, 窪木拓男, 滝川正春

    第1回日本CCN研究会  2007.10 

    　More details

  • 長管骨組織におけるEphA4の分布と遺伝子発現の解析

    黒田知沙, 久保田聡, 河田かずみ, 皆木省吾, 滝川正春

    第28回岡山歯学会学術大会  2007.8 

    　More details

  • 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

    河田かずみ, 久保田聡, 江口傑徳, 青山絵理子, 川木晴美, 岡森彦, 皆木省吾, 滝川正春

    第17回中国・四国骨代謝研究会  2007.7 

    　More details

  • 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

    第25回日本骨代謝学会学術集会  2007.7 

    　More details

  • 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, 久保田聡, 江口傑徳, 青山絵理子, 川木晴美, 岡森彦, 皆木省吾, 滝川正春

    第20回日本軟骨代謝学会  2007.3 

    　More details

  • 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

    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, 田中真二, 滝川正春

    第20回日本軟骨代謝学会  2007.3 

    　More details

  • Expression and possible function of a CCN2 receptor, low density lipoprotein receptor-related protein 1 (LRP1), in chondrocytes

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

    Forth international workshop on the CCN family of genes  2006.10 

    　More details

  • Wnt-induced protein1 (WISP1/CCN4) mRNA splicing variants in normal and transformed chondrocytes

    Yanagita T, Kubota S, Kawata K, Kawaki H, Takano-Yamamoto T, Takana S, Takigawa M

    Forth international workshop on the CCN family of genes  2006.10 

    　More details

  • ラット大腿骨骨欠損におけるCTGF/CCN2の効果

    菊地剛, 浅海浩二, 三谷茂, 尾崎敏文, 久保田聡, 河田かずみ, 滝川正春, 田畑康彦

    第24回日本骨代謝学会学術集会  2006.7 

    　More details

  • 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

    第24回日本骨代謝学会学術集会  2006.7 

    　More details

  • Expression and possible function of the low density lipoprotein receptor-related protein 1 (LRP1) in chondrocytes

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

    20th IUBMB international congress of biochemistry and molecular biology and 11th FAOBMB congress  2006.6 

    　More details

  • Two Wnt-induced secreted protein1 (WISP1/CCN4) mRNA splicing variants in normal and transformed chondrocytes

    Yanagita T, Kubota S, Kawata K, Kawaki H, Kondo S, Takano-Yamamoto T, Takigawa M

    20th IUBMB international congress of biochemistry and molecular biology and 11th FAOBMB congress  2006.6 

    　More details

  • 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

    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

    第19回日本軟骨代謝学会  2006.3 

    　More details

  • 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

    柳田剛志, 久保田聡, 河田かずみ, 川木晴美, 近藤誠二, 山本照子, 田中真二, 滝川正春

    第19回日本軟骨代謝学会  2006.3 

    　More details

  • 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(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

    第28回日本分子生物学会  2005.12 

    　More details

  • MMP3/Stromelysin-1 acts as atranscription modulator targeting ccn2 in chondrocytes

    Eguchi T, Kubota S, Mukudai Y, Kawata K, Ibaragi S, Uehara J, Kondo S, Ogawara T, Takigawa M

    第28回日本分子生物学会  2005.12 

    　More details

  • Differential expression of CCN4/Wisp1 mRNA splicing variants in normal and malignant-transformed chondrocytes

    Yanagita T, Kubota S, Kawata K, Kawaki H, Takano-Yamamoto T, Tanaka S, Takigawa M

    第53回国際歯科研究学会学術大会  2005.11 

    　More details

  • ヒト軟骨肉腫由来細胞株(HCS-2/8)におけるWnt-induced secreted protein 1 (WISP1/CCN4) mRNAの新規splicing variantの発見

    柳田剛志, 久保田聡, 服部高子, 星島光博, 河田かずみ, 山本照子, 滝川正春

    第78回日本生化学会  2005.10 

    　More details

  • 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

    第23回日本骨代謝学会  2005.7 

    　More details

  • 二次骨化中心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

    第23回日本骨代謝学会  2005.7 

    　More details

  • 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

    久保田聡, 西田崇, 河田かずみ, 柳田剛志, 窪木拓男, 田畑泰彦, 滝川正春

    第37回日本結合組織学会  2005.5 

    　More details

  • 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

    第18回日本軟骨代謝学会  2005.3 

    　More details

  • 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

    第18回日本軟骨代謝学会  2005.3 

    　More details

  • 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

    第27回日本分子生物学会年会  2004.12 

    　More details

  • Expression of the low density lipoprotein receptor-related protein1 (LRP1) in chondrocytes

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

    第77回日本生化学会大会  2004.10 

    　More details

  • Differential regulation of CTGF/CCN2 transcription in MDA231 breast cancer cell line and HCS-2/8 chondrocytic cell line

    Eguchi T, Kubota S, Kawata K, Ogawara T, Mukudai Y, Takigawa M

    Third International Workishop on the CCN Family of Genes  2004.10 

    　More details

  • Quantitative evaluation of connective tissue growth factor (CTGF/CCN2) in human platelets

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

    第77回日本生化学会大会  2004.10 

    　More details

  • 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)

    久保田聡, 河田かずみ, 柳田剛志, 土井英之, 滝川正春

    第22回日本骨代謝学会学術集会  2004.8 

    　More details

  • 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

    第22回日本骨代謝学会学術集会  2004.8 

    　More details

  • 血小板に見出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)

    河田かずみ, 久保田聡, 柳田剛志, 皆木省吾, 滝川正春

    第17回日本軟骨代謝学会  2004.3 

    　More details

  • 非翻訳領域を介したctgf/ccn2とcyr61/ccn1の遺伝子発現制御

    久保田聡, 湊雅直, 森谷徳文, 椋代義樹, 中尾匡志, 河田かずみ, 滝川正春

    第26回日本分子生物学会年会  2003.12 

    　More details

▼display all

Awards

  • 優秀ディスカッション賞

    2016.11   Skeletal Science Retreat 2016  

    　More details

    Country：Japan

    researchmap

  • ANZBMS 2013 Travel Award

    2013.5   日本骨代謝学会  

    　More details

    Country：Japan

    researchmap

  • 優秀演題賞

    2013.5   日本骨代謝学会  

    河田 かずみ

    　More details

  • 奨励論文賞

    2011.11   岡山歯学会  

    河田 かずみ

    　More details

  • 若手国際学術奨励賞

    2011.8   日本CCNファミリー研究会  

    河田 かずみ

    　More details

  • 優秀演題賞

    2011.6   日本結合組織学会  

    河田 かずみ

    　More details

▼display all

Research Projects

  • 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

    　 More details

    Grant amount：\25740000 （ Direct expense: \19800000 、 Indirect expense：\5940000 ）

    researchmap

  • 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)  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

    　 More details

    Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）

    researchmap

  • 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)  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

    　 More details

    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。

    researchmap

  • Regulation of skeletogenesis by long noncoding RNAs through CCN2

    Grant number：21H03105  2021.04 - 2025.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    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

    　 More details

    Grant amount：\17160000 （ Direct expense: \13200000 、 Indirect expense：\3960000 ）

    本研究を支える２つの柱は、cellular communication network factor 2 (CCN2) 遺伝子をトランスに制御する長鎖非コードRNA (lncRNA) であるurothelial cancer associated 1 (UCA1) と、シスに制御するanti-CCN2 3'-UTR RNA (ACUR) である。
    まずUCA1については、当該lncRNAの作動エレメント、つまり軟骨細胞分化を促進するRNA上の機能領域を突き止めるためin silicoでUCA1の構造を予測し、順に欠損させた３つの変異体を発現するシステムを、レンチウイルスベクターを用いて構築し、それらベクターを使って標的であるマウスATDC5細胞でこれら変異体を強制発現できることを確認できた。またUCA1が吸着しうるmiRNAを探索し、現在までに37のmiRNAをUCA1によって軟骨細胞内で制御されうる分子として特定できた。さらに新たな展開として、UCA1が骨芽細胞機能に与える影響を、軟骨細胞と同じ戦略、すなわちUCA1を持たないマウスMC3T3-E1細胞にレンチウイルスベクターで強制発現させ、骨芽細胞マーカー遺伝子の発現定量やアルカリホスファターゼ染色で評価した。しかしながら軟骨細胞とは異なり骨芽細胞形質はUCA1の影響を受けなかった。以前の研究で、間葉系幹細胞が骨芽細胞へ分化する際、UCA1発現は減少することも確認している。以上の所見は、UCA1が軟骨細胞において高度に特異的な機能を発揮していることを示唆している。
    そしてACURについては、センスRNA、つまりCCN2 RNA には影響を与えることなくアンチセンスRNAのみを、RNase H活性により特異的に分解するGapmeRを５種類設計・合成し、ヒト軟骨細胞様HCS-2/8細胞に導入して関連遺伝子発現量を評価した。その結果、５種のうち２種のGapmeRによって効率よくACURのサイレンシングが起こることが確認され、その状況下ではCCN2遺伝子ばかりでなく、軟骨細胞マーカー遺伝子も抑制される傾向にあった。つまり骨格形成に対してインパクトを与えている可能性が濃厚となった。

    researchmap

  • 新規軟骨老化促進因子CCN3の加齢に伴った発現誘導と細胞周期停止機構の解明

    Grant number：21K09815  2021.04 - 2024.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    服部 高子, 久保田 聡, 西田 崇, 高江洲 かずみ

    　 More details

    Grant amount：\4160000 （ Direct expense: \3200000 、 Indirect expense：\960000 ）

    １．胎生期から出生後37週（8.6ヶ月齢）までの様々な時期のマウス肋軟骨組織から初代培養軟骨細胞を単離し、遺伝子発現の変化を調べると、CCN family member 3 (CCN3) mRNAとともに細胞周期停止因子p21, p53、senescence-associated secretory phenotype (SASP)因子であるIL-6, IL-8 mRNAの発現レベルと軟骨細胞採取時のマウスの加齢状態との間に強い正の相関があることがわかった。また、CCN3抗体を用いた1ヶ月から7ヶ月齢のマウス膝関節の免疫染色でも、加齢とともに強い染色性が観察された。２．ヒト患者由来初代培養軟骨細胞、ラット培養軟骨細胞株RCSに酸化ストレスとしてH2O2を添加し、人工的に誘発した老化軟骨細胞においてCCN3 mRNAの有意な発現上昇とともに、p21,p53の発現上昇、肥大軟骨マーカーである10型コラーゲン、マトリックスメタロプロテナーゼ13、アグリカン分解酵素ADAMTS5 mRNAの発現誘導が認められ、CCN3、P53の誘導は蛋白レベルでも確かめられた。この時、senescence-associated (SA)-β galactosidaseの活性化も確認された。３．RCS細胞にCCN3を発現ベクターの導入により過剰発現させるとp21プロモータ活性が上昇した。４．２週齢マウス膝関節より単離された初代培養軟骨細胞およびRCS細胞に組換えCCN3蛋白を添加するとp21, p53 mRNAが誘導された。これらのことからCCN3の発現上昇によっても細胞周期停止因子の誘導による老化が誘発されることが明らかとなった。５．軟骨組織特異的にCCN3を発現するトランスジェニックマウスの関節軟骨では、早期に関節変性が誘導され、このマウスの肋軟骨組織から単離した初代培養軟骨細胞では細胞周期停止因子群、SASP因子群の発現が上昇していた。６．ヒト患者由来関節組織から単離した初代培養軟骨細胞においてCCN3, p21,p53 mRNAの発現レベルと年齢との間に強い正の相関が観察された。

    researchmap

  • 長鎖非コードRNAによる骨細胞メカニカルストレス応答制御機構の解明

    Grant number：21K10189  2021.04 - 2024.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    石川 崇典, 宮脇 正一, 前田 綾, 大賀 泰彦, 久保田 聡, 西田 崇, 服部 高子, 高江洲 かずみ

    　 More details

    Grant amount：\4160000 （ Direct expense: \3200000 、 Indirect expense：\960000 ）

    最近、タンパク質をコードしない長鎖非コードRNAが様々な生理的機能に関与していることが明らかとなっている。しかしながら、矯正歯科治療における歯の移動において極めて重要な生体反応である、骨細胞のメカニカルストレス応答に関与するとされる長鎖非コードRNAの報告はまだない。そこで、本研究では骨細胞のメカニカルストレス応答下で機能する長鎖非コードRNAを特定し、その詳細な分子機構を明らかにすることを目的とし、研究を実施している。
    目的とする長鎖非コードRNAを特定するため、マイクロアレイによる網羅的遺伝子発現解析を予定しており、初年度はまず実施するサンプルの条件を検討した。骨細胞様細胞株MLO-Y4細胞を培養し、同細胞に様々な種類のメカニカルストレスを負荷後、同サンプルを回収し、骨芽細胞マーカー遺伝子および骨芽細胞分化に関与しているとされる長鎖非コードRNAを定量RT-PCRにより評価し、マイクロアレイを実施するサンプルの選定を行った。初年度末の時点で概ね本作業は完了しており、今後はコントロール群と比較し遺伝子変動の大きかった方法でメカニカルストレスを付与したMLO-Y4細胞を準備し、網羅的遺伝子発現解析を実施していく。同サンプルの解析結果より、特定の長鎖非コードRNAの遺伝子発現の上昇もしくは低下が確認できると考えており、2年目以降では、その中で特に遺伝子発現の変動が多かったRNAをin vitroにてノックダウンおよび強制発現させ、骨代謝マーカー遺伝子の発現変動を確認し詳細な機能を調査することとしている。

    researchmap

  • 象牙芽前駆細胞におけるIFT88を介した細胞増殖制御機構の解明

    2021

    岡山大学ダイバーシティ推進本部男女共同参画室  女性教員支援助成金【研究費配分型】 

    　 More details

  • 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

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (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

    　 More details

    Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）

    線維性疾患は組織内にコラーゲンが過剰に沈着し、正常な組織機能が損なわれる慢性疾患である。近年、筋線維芽細胞が線維化のキープレイヤーとして注目されているが、その分化機構は未だ不明である。本研究課題の目的は線維化の進行に重要な役割を担うと考えられているCellular communication network factor 2 (CCN2)が筋線維芽細胞の分化にどのように関わっているのかをイントラクリン作用の観点から解明することである。当該年度では、未分化間葉系細胞株C3H10T1/2細胞を用いてCCN2にイントラクリン様の作用を誘導し、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の発現プラスミド(SP-Ccn2)を構築し、C3H10T1/2細胞に遺伝子導入した。対照群としてシグナルペプチドを付加したCCN2の発現プラスミド(SP+Ccn2)を用いた。CCN2が核内に移行するかを蛍光免疫染色で調べた結果、SP+Ccn2を遺伝子導入した細胞ではCCN2が細胞質に局在したのに対し、SP-Ccn2を遺伝子導入した細胞ではCCN2は一部核内に見られた。
    2.1.で作製した発現プラスミドをC3H10T1/2細胞に遺伝子導入し、筋線維芽細胞分化に重要な転写因子であるPU.1の遺伝子発現レベルを定量RT-PCR法で解析した。結果、SP+Ccn2を遺伝子導入した群ではempty vector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PU.1の遺伝子発現レベルが有意に上昇した。
    3.PU.1の標的分子であるテネイシンC及びPDGFの産生量をWestern blot解析で調べた結果、SP-Ccn2を導入した群で両分子の産生量の増加が見られた。

    researchmap

  • 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)  Grant-in-Aid for Challenging Research (Exploratory)

    Kubota Satoshi

    　 More details

    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.

    researchmap

  • 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 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (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

    　 More details

    Grant amount：\4420000 （ Direct expense: \3400000 、 Indirect expense：\1020000 ）

    日本人の平均寿命は年々伸びている反面、健康寿命は伸びていない。健康寿命を延長には咀嚼機能の維持が鍵となるため、歯牙の再生療法の開拓が望まれている。個々の歯牙の再建には象牙質の再生が必須であるが、自然状態での象牙質再生能力は不充分である。
    このため、象牙芽細胞の細胞外環境感知センサー、つまり〝一次繊毛”の形成や細胞周期の制御に機能するIntraflagellar transport (Ift) 88を機能制御することで、象牙質再生の実現を我々は目指している。理想的な形質・形態の象牙質を再生するためには、まず正常象牙質の形成過程を解明する必要がある。そのために、まず、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を検討する。その上で、象牙質再生法の開発を検討していく。
    現在までに、Ift 88をノックダウンした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、細胞接着能力や細胞増殖速度が抑制されることを確認している。本年度は、KN-3細胞において、IFT88が細胞接着や細胞増殖を調節する機構を検討するため、Fucci-S/G2/M Green expression KN-3細胞を作製し、細胞周期のモニタリングをArrayScanを用いて行った。その結果、sh-Ift88 KN-3細胞では、コントロールのKN-3細胞と比較して、Fucci-S/G2/M Greenの発現が抑制されていることが明らかとなった。

    researchmap

  • 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)  Grant-in-Aid for Challenging Research (Exploratory)

    Kubota Satoshi

    　 More details

    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.

    researchmap

  • 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)  Grant-in-Aid for Scientific Research (C)

    Nishida Takashi

    　 More details

    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.

    researchmap

  • The investigation of the mechanism of regular arrangement of odontoblasts via extracellular environment sensing sensors

    Grant number：16K11475  2016.04 - 2019.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Takaesu Kazumi

    　 More details

    Authorship：Principal investigator  Grant type：Competitive

    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.

    researchmap

  • Role of Sox9 and its ubiquitin ligase on the Circadian growth rhythm in chondrocytes

    Grant number：16K11476  2016.04 - 2019.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Hattori Takako

    　 More details

    Grant amount：\4680000 （ Direct expense: \3600000 、 Indirect expense：\1080000 ）

    1. Gene expression of melatonin-synthesizing enzymes and melatonin receptors wes detected in mouse primary chondrocytes. 2. Production of melatonin in chondrocytes was confirmed by mass spectrophotometric analysis. 3. Melatonin enhanced chondrocyte growth and increased expression of chondrocyte markers, but inhibited hypertrophy. These effects was abolished by addition of an antagonist. 4. Melatonin rapidly upregulaed a melatonin synthesizing enzyme and receptor expression and expression of the clock gene Bmal1, while downregulated Per1. 5. Chronobiological analysis of C3H mouse chondrocytes, which express melatonin, revealed that melatonin induced the cyclic expression of melatonin and modified the cyclic rhythm of Bmal1, Mt1 and Mt2, but not in BALB/c mouse chondrocytes. These results indicate that exogenous and endogenous melatonin works in synergy in chondrocytes to adjust rhythmic expression to the central suprachiasmatic nucleus clock.

    researchmap

  • 細胞「外」小器官を介した象牙芽細胞の規則的配列機構の解明

    2015

    復職支援助成金 

    河田 かずみ

    　 More details

    Authorship：Principal investigator  Grant type：Competitive

    researchmap

  • 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  Grant-in-Aid for Challenging Exploratory Research

    TAKIGAWA MASAHARU, KUBOTA SATOSHI, AOYAMA ERIKO, NISHIDA TAKASHI, HATTORI TAKAKO, TAKAESU KAZUMI

    　 More details

    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.

    researchmap

  • Development of a new regenerative treatment for teeth through cellular antennas

    Grant number：25870277  2013.04 - 2015.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)  Grant-in-Aid for Young Scientists (B)

    KAWATA Kazumi

    　 More details

    Authorship：Principal investigator  Grant type：Competitive

    The aim of this study is tooth preservation that leads to health maintenance of a whole body. For the tooth preservation, teeth with dental caries need to be revived. However, there are no regenerative treatments to decayed teeth at present. On the other hand, a primary cilium function as a cellular antenna on most cells in a body. Moreover, primary cilia are known to exist in odontoblasts as well. However, functions of primary cilia in odontoblasts are still unknown.
    In this study, the mechanism of odontoblastic differentiation through primary cilia was elucidated. Furthermore, steroid dexamethasone is known to differentiate dental pulp cells to odontoblasts. We revealed that the effect depends on primary cilia.
    From now on, we intend to develop new regenerative treatment methods for teeth which received damage by dental caries based on these observations.

    researchmap

  • 変形性関節症発症に於ける一次繊毛の役割 -新規治療法の開発に向けて -

    2013

    公益財団法人金原一郎記念医学医療振興財団  第28回基礎医学医療研究助成金 

    河田 かずみ

    　 More details

    Authorship：Principal investigator  Grant type：Competitive

    researchmap

  • 軟骨組織におけるLRP1のCCN2/CTGFタンパク輸送体としての機能：変異動物を用いた解析

    2011

    特別教育研究経費「口腔からQOL向上を目指す連携研究」研究スカラーシップ 

    河田 かずみ

    　 More details

    Authorship：Principal investigator  Grant type：Competitive

    researchmap

  • Function of the low-density lipoprotein receptor related protein 1 (LRP1) as a transporter of CCN2/connective tissue growth factor (CTGF) in chondrocytes

    2011

    特別教育研究経費「口腔からQOL向上を目指す連携研究」国際学会等派遣 

    河田 かずみ

    　 More details

    Authorship：Principal investigator  Grant type：Competitive

    researchmap

  • 軟骨組織でのLRP1のCCN2/CTGFタンパク質輸送における役割：顎関節症と変形性関節症の治療にむけて

    2010

    両備てい園記念財団  研究助成金 

    河田 かずみ

    　 More details

    Authorship：Principal investigator  Grant type：Competitive

    researchmap

  • 軟骨組織でのCCN2/CTGF受容体LRP1のタンパク輸送における役割：新たな変形性関節症治療にむけて

    2010

    特別教育研究経費「口腔からQOL向上を目指す連携研究」研究スカラーシップ 

    河田 かずみ

    　 More details

    Authorship：Principal investigator  Grant type：Competitive

    researchmap

  • Role of the low-density lipoprotein receptor related protein 1 (LRP1) in CCN2/CTGF protein transportation in chondrocytes

    2010

    特別教育研究経費「口腔からQOL向上を目指す連携研究」国際学会等派遣 

    河田 かずみ

    　 More details

    Authorship：Principal investigator  Grant type：Competitive

    researchmap

  • Prevention of dementia by the recovery of the mastication

    Grant number：21592448  2009 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    HARA Tetsuya, NAKANISHI Tohru, KODAMA Chie, KAWATA Kazumi, MINAGI Shogo

    　 More details

    Grant amount：\4680000 （ Direct expense: \3600000 、 Indirect expense：\1080000 ）

    The memory related gene expression in the rat hippocampus was analyzed by using the DNA microarray method. The gene expression of Trh and Tnxa increased when studying, and that of Nnat and S100a9 decreased. The number of errors of radial maze in the extraction group was more than that of the denture group and the control group. The time course of these 4 gene expression was observed by real-time PCR method. The gene expression of Tnxa Nnat and S100a9 showed the consistency with behavioral experiment result.

    researchmap

  • 軟骨分化におけるLRP1の機能:シグナル受容体及びタンパク質輸送体としての役割

    Grant number：21791893  2009 - 2010

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)  Grant-in-Aid for Young Scientists (B)

    河田 かずみ

    　 More details

    Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）

    1,計画に従い、siRNAを用いヒト軟骨細胞様細胞株HCS-2/8細胞でのthe low density lipoprotein receptor related protein 1(lrp1)の発現をノックダウンし、real-time PCRにより軟骨分化マーカー遺伝子発現の変動を検討した結果、成熟軟骨細胞分化マーカー遺伝子であるaggrecanとcol2a1 mRNAは減少した一方、肥大軟骨細胞マーカー遺伝子であるmmp13 mRNAは増加した。また、古典的WNTシグナル経路が活性化することを確認した。次にHCS-2/8細胞でLRP1を強制発現したところ、古典的WNTシグナル経路の抑制が認められ、lrp1ノックダウン時と逆の結果を示した。尚、HCS-2/8細胞へのPKCζ inhibitorの添加により、lrp1ノックダウン時と同様の軟骨分化マーカー遺伝子発現の変動を示した。
    2, lrp1ノックダウンHCS-2/8細胞では、PKCζ特異的にリン酸化を抑制することも確認した。次にHCS-2/8細胞でLRP1を強制発現したところ、PKCζの特異的な活性化が認められ、lrp1ノックダウン時と逆の結果を示した。尚、HCS-2/8細胞へのPKCζ inhibitorの添加により、lrp1ノックダウン時と同様の軟骨細胞分化マーカー遺伝子発現の変動を示した。
    3, ニワトリ胸骨から静止軟骨細胞、増殖軟骨細胞、肥大軟骨細胞をそれぞれ単離し、lrp1の発現をノックダウンしたところ、肥大軟骨細胞のみ、HCS-2/8細胞でのlrp1ノックダウン時と同様の軟骨細胞分化マーカー遺伝子発現の変動を示した。
    以上の結果は、LRP1が古典的WNTシグナル経路だけでなく、さらにはPKC経路をも調節することによって軟骨細胞分化を制御し、この効果は細胞分化段階によって異なる可能性を強く示唆するものである。

    researchmap

  • 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）の機能：シグナル受容体及びタンパク質輸送体としての役割

    2008

    特別教育研究経費「口腔からQOL向上を目指す連携研究」研究スカラーシップ 

    河田 かずみ

    　 More details

    Authorship：Principal investigator  Grant type：Competitive

    researchmap

▼display all

 

Class subject in charge

  • Molecular Dentistry Demonstration （2023academic year） Fourth semester  - 水4,水5,水6,水7,木1,木2,木3

  • Seminar in Biochemistry and Molecular Dentistry （2023academic year） Fourth semester  - 水4,水5,水6,水7,木1,木2,木3

  • Practicals: Biochemistry and Molecular Dentistry （2023academic year） special  - その他

  • Research Projects: Biochemistry and Molecular Dentistry （2023academic year） special  - その他

  • Research Projects and Practicals: Biochemistry and Molecular Dentistry I （2023academic year） special  - その他

  • Lecture and Research Projects: Biochemistry and Molecular Dentistry I （2023academic year） special  - その他

  • Research Projects and Practicals: Biochemistry and Molecular Dentistry II （2023academic year） special  - その他

  • Lecture and Research Projects: Biochemistry and Molecular Dentistry II （2023academic year） special  - その他

  • Structure, Function and Metabolism of Biological Molecules （2023academic year） 1st semester  - 木1,木2,木3

  • Biochemistry （2023academic year） Concentration  - その他

  • tutorial （2022academic year） 1st semester  - 火4,火5,火6,火7

  • Molecular Dentistry Demonstration （2022academic year） Fourth semester  - 水4,水5,水6,水7,木1,木2,木3

  • Seminar in Biochemistry and Molecular Dentistry （2022academic year） Fourth semester  - 水4,水5,水6,水7,木1,木2,木3

  • Research Projects and Practicals: Biochemistry and Molecular Dentistry I （2022academic year） special  - その他

  • Lecture and Research Projects: Biochemistry and Molecular Dentistry I （2022academic year） special  - その他

  • Research Projects and Practicals: Biochemistry and Molecular Dentistry II （2022academic year） special  - その他

  • Lecture and Research Projects: Biochemistry and Molecular Dentistry II （2022academic year） special  - その他

  • Structure, Function and Metabolism of Biological Molecules （2022academic year） 1st semester  - 木1,木2,木3

  • Biochemistry （2022academic year） Concentration  - その他

  • tutorial （2021academic year） 1st semester  - 火4,火5,火6,火7

  • Molecular Dentistry Demonstration （2021academic year） Fourth semester  - 水4,水5,水6,水7,木1,木2,木3

  • Seminar in Biochemistry and Molecular Dentistry （2021academic year） Fourth semester  - 水4,水5,水6,水7,木1,木2,木3

  • Research Projects and Practicals: Biochemistry and Molecular Dentistry I （2021academic year） special  - その他

  • Lecture and Research Projects: Biochemistry and Molecular Dentistry I （2021academic year） special  - その他

  • Research Projects and Practicals: Biochemistry and Molecular Dentistry II （2021academic year） special  - その他

  • Lecture and Research Projects: Biochemistry and Molecular Dentistry II （2021academic year） special  - その他

  • Biochemistry （2021academic year） Concentration  - その他

  • tutorial （2020academic year） 1st semester  - 火4,火5,火6,火7

  • Molecular Dentistry Demonstration （2020academic year） Fourth semester  - 水4,水5,水6,水7,木5,木6,木7

  • Seminar in Biochemistry and Molecular Dentistry （2020academic year） Fourth semester  - 水4,水5,水6,水7,木5,木6,木7

  • Research Projects and Practicals: Biochemistry and Molecular Dentistry I （2020academic year） special  - その他

  • Lecture and Research Projects: Biochemistry and Molecular Dentistry I （2020academic year） special  - その他

  • Research Projects and Practicals: Biochemistry and Molecular Dentistry II （2020academic year） special  - その他

  • Lecture and Research Projects: Biochemistry and Molecular Dentistry II （2020academic year） special  - その他

  • Biochemistry （2020academic year） Concentration  - その他

  • tutorial （2019academic year） 1st semester  - 火4,火5,火6,火7

  • Molecular Dentistry Demonstration （2019academic year） Fourth semester  - 水4,水5,水6,水7,木1,木2,木3

  • Molecular Dentistry Demonstration （2019academic year） Fourth semester  - 水4,水5,水6,水7,木1,木2,木3

  • Seminar in Biochemistry and Molecular Dentistry （2019academic year） Fourth semester  - 水4,水5,水6,水7,木1,木2,木3

  • Research Projects and Practicals: Biochemistry and Molecular Dentistry I （2019academic year） special  - その他

  • Lecture and Research Projects: Biochemistry and Molecular Dentistry I （2019academic year） special  - その他

  • Research Projects and Practicals: Biochemistry and Molecular Dentistry II （2019academic year） special  - その他

  • Lecture and Research Projects: Biochemistry and Molecular Dentistry II （2019academic year） special  - その他

  • Biochemistry （2019academic year） Concentration  - その他

  • tutorial （2018academic year） 1st semester  - 火4,火5,火6,火7

  • Molecular Dentistry Demonstration （2018academic year） Fourth semester  - 水4,水5,水6,水7,木1,木2,木3

  • Seminar in Biochemistry and Molecular Dentistry （2018academic year） Fourth semester  - 水4,水5,水6,水7,木1,木2,木3

  • Research Projects and Practicals: Biochemistry and Molecular Dentistry I （2018academic year） special  - その他

  • Lecture and Research Projects: Biochemistry and Molecular Dentistry I （2018academic year） special  - その他

  • Research Projects and Practicals: Biochemistry and Molecular Dentistry II （2018academic year） special  - その他

  • Lecture and Research Projects: Biochemistry and Molecular Dentistry II （2018academic year） special  - その他

▼display all

 

Media Coverage

  • ヒューマニエンス～40億年のたくらみ～ミクロの毛 細胞を 指揮する司令塔 TV or radio program

    NHK BSP/BS4K  2022.11

    　More details