Updated on 2025/01/18

写真a

 
Suzuki Shigeki
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Professor
Position
Professor
Contact information
メールアドレス
External link

Degree

  • 歯学博士 ( 大阪大学 )

Research Interests

  • 歯科保存学

  • 細胞外基質

  • エピジェネティクス

  • 分子生物学

  • エピゲノム

  • 歯周組織再生

  • 歯周病学

  • 歯内療法学

  • 象牙質再生

Research Areas

  • Life Science / Conservative dentistry

  • Life Science / Genome biology

  • Life Science / Regenerative dentistry and dental engineering

  • Life Science / Molecular biology

Education

  • Osaka University   歯学研究科   口腔分子免疫制御学 歯周病分子病態学

    2002.4 - 2006.3

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  • Osaka University   歯学部   歯学科

    1996.4 - 2002.3

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  • Kyoto University of Education    

    1993.4 - 1996.3

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Research History

  • 岡山大学学術研究院医歯薬学域 大学院医歯薬学総合研究科   教授

    2024.10

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  • Tohoku University   Graduate School of Dentistry   Lecturer

    2018.4 - 2024.9

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  • 広島大学大学院医歯薬保健学研究院 統合健康科学部門   講師

    2016.8 - 2018.3

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  • 広島大学大学院医歯薬保健学研究院   助教

    2012.4 - 2016.7

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  • Stanford University (USA), Visiting scholar

    2011.7 - 2011.9

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  • 広島大学大学院医歯薬総合研究科   助教

    2009.4 - 2012.3

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  • National Institute of Dental and Craniofacial Research, National Institutes of Health (USA)   Visiting fellow

    2006.8 - 2009.3

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  • Osaka University   Graduate School of Dentistry

    2006.4 - 2006.7

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Professional Memberships

  • JAPANESE SOCIETY OF PERIODONTOLOGY

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  • THE JAPANESE SOCIETY OF CONSERVATIVE DENTISTRY

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  • JAPANESE ASSOCIATION FOR ORAL BIOLOGY

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  • JAPAN ENDODONTIC ASSOCIATION

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Committee Memberships

  • 日本歯内療法学会   倫理・利益相反委員会  

    2024.4   

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  • 日本歯科保存学会   選挙管理委員会委員  

    2023.4   

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  • 日本歯周病学会   ペリオドンタルメディシン委員会委員  

    2021.4 - 2023.3   

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  • 日本歯科保存学会   選挙管理委員会委員  

    2021.4 - 2023.3   

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  • 日本歯科保存学会   ポスター審査委員  

    2021.4 - 2023.3   

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  • 日本歯科保存学会   編集連絡委員会委員  

    2019.7   

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  • 日本歯周病学会   若手合宿研修ワーキングメンバー  

    2018.9   

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  • 日本歯科保存学会   編集連絡委員会委員  

    2015.6 - 2018.3   

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  • 日本歯科保存学会   評議員  

    2015.4   

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Papers

  • Periodontal ligament fibroblasts utilize isoprenoid intermediate farnesyl diphosphate for maintaining osteo/cementogenic differentiation abilities Reviewed

    Xiuting Wang, Shigeki Suzuki, Hang Yuan, Shizu Hirata-Tsuchiya, Rahmad Rifqi Fahreza, Eiji Nemoto, Hideki Shiba, Satoru Yamada

    Journal of Dental Sciences   2025.1

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    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jds.2024.04.025

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  • Effects of Low-intensity Pulsed Ultrasound on Bone Formation with Gelatin Hydrogel Containing Bone Morphogenetic Protein-2 Reviewed

    Yamaji Kozo, Yokoyama Akihito, Sugaya Tsutomu, Matsuzaki Kumiko, Takahashi Kei, Shinno Yasuo, Ohara Naoko, Suzuki Shigeki

    J Oral Tissue Engin   22(2)   2024.12

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

    DOI: 10.11223/jarde.22.53

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  • Role of transglutaminase 2 in promoting biglycan synthesis in idiopathic gingival fibromatosis Reviewed

    Yurika Ninomiya, Shinji Matsuda, Shigeki Suzuki, Shizu Hirata-Tsuchiya, Tomoya Ueda, Fuminori Nakashima, Keisuke Yasuda, Shogo Shimada, Takumi Memida, Tetsuya Yoshimoto, Satoru Yamada, Kazuhisa Ouhara, Noriyoshi Mizuno

    BMC Oral Health   24 ( 1 )   2024.11

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

    DOI: 10.1186/s12903-024-05211-8

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    Other Link: https://link.springer.com/article/10.1186/s12903-024-05211-8/fulltext.html

  • Cementocyte-derived extracellular vesicles regulate osteoclastogenesis and osteoblastogenesis Reviewed

    Jiajun Li, Yukihiko Sakisaka, Eiji Nemoto, Kentaro Maruyama, Shigeki Suzuki, Kaixin Xiong, Hiroyuki Tada, Taichi Tenkumo, Satoru Yamada

    Journal of Dental Sciences   2024.10

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jds.2024.02.025

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  • Dynamic changes in chromatin accessibility during the differentiation of dental pulp stem cells reveal that induction of odontogenic gene expression is linked with specific enhancer construction Reviewed

    Kento Sasaki, Shigeki Suzuki, Rahmad Rifqi Fahreza, Eiji Nemoto, Satoru Yamada

    Journal of Dental Sciences   2024.7

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    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jds.2023.10.022

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  • The histone deacetylase inhibitor MS-275 enhances the matrix mineralization of dental pulp stem cells by inducing fibronectin expression Reviewed

    Shigeki Suzuki, Kento Sasaki, Rahmad Rifqi Fahreza, Eiji Nemoto, Satoru Yamada

    Journal of Dental Sciences   2024.7

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

    DOI: 10.1016/j.jds.2023.11.019

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  • A triple growth factor strategy for optimizing bone augmentation in mice Reviewed

    Taichi Tenkumo, Rie Koide, Toru Ogawa, Hirofumi Yamaguchi, Shigeki Suzuki, Makiko Miyashita, Keisuke Nakamura, Han Wang, Nobuhiro Yoda, Keiichi. Sasaki

    Journal of Biomedical Materials Research: Part B - Applied Biomaterials   2024.6

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  • Periodontal inflammation potentially inhibits hepatic cytochrome P450 expression and disrupts the omega-3 epoxidation pathway in a murine model Reviewed

    Yoshino Daidouji, Shigeki Suzuki, Xiuting Wang, Rahmad Rifqi Fahreza, Eiji Nemoto, Satoru Yamada

    Journal of Dental Sciences   2024.5

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.jds.2024.05.028

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  • Mice Lacking PLAP-1/Asporin Show Alteration of Periodontal Ligament Structures and Acceleration of Bone Loss in Periodontitis Reviewed

    Masaki Kinoshita, Satoru Yamada, Junichi Sasaki, Shigeki Suzuki, Tetsuhiro Kajikawa, Tomoaki Iwayama, Chiharu Fujihara, Satoshi Imazato, Shinya Murakami

    International Journal of Molecular Sciences   24 ( 21 )   15989 - 15989   2023.11

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

    Periodontal ligament-associated protein 1 (PLAP-1), also known as Asporin, is an extracellular matrix protein expressed in the periodontal ligament and plays a crucial role in periodontal tissue homeostasis. Our previous research demonstrated that PLAP-1 may inhibit TLR2/4-mediated inflammatory responses, thereby exerting a protective function against periodontitis. However, the precise roles of PLAP-1 in the periodontal ligament (PDL) and its relationship to periodontitis have not been fully explored. In this study, we employed PLAP-1 knockout mice to investigate its roles and contributions to PDL tissue and function in a ligature-induced periodontitis model. Mandibular bone samples were collected from 10-week-old male C57BL/6 (WT) and PLAP-1 knockout (KO) mice. These samples were analyzed through micro-computed tomography (μCT) scanning, hematoxylin and eosin (HE) staining, picrosirius red staining, and fluorescence immunostaining using antibodies targeting extracellular matrix proteins. Additionally, the structure of the PDL collagen fibrils was examined using transmission electron microscopy (TEM). We also conducted tooth extraction and ligature-induced periodontitis models using both wild-type and PLAP-1 KO mice. PLAP-1 KO mice did not exhibit any changes in alveolar bone resorption up to the age of 10 weeks, but they did display an enlarged PDL space, as confirmed by μCT and histological analyses. Fluorescence immunostaining revealed increased expression of extracellular matrix proteins, including Col3, BGN, and DCN, in the PDL tissues of PLAP-1 KO mice. TEM analysis demonstrated an increase in collagen diameter within the PDL of PLAP-1 KO mice. In line with these findings, the maximum stress required for tooth extraction was significantly lower in PLAP-1 KO mice in the tooth extraction model compared to WT mice (13.89 N ± 1.34 and 16.51 N ± 1.31, respectively). In the ligature-induced periodontitis model, PLAP-1 knockout resulted in highly severe alveolar bone resorption, with a higher number of collagen fiber bundle tears and significantly more osteoclasts in the periodontium. Our results demonstrate that mice lacking PLAP-1/Asporin show alteration of periodontal ligament structures and acceleration of bone loss in periodontitis. This underscores the significant role of PLAP-1 in maintaining collagen fibrils in the PDL and suggests the potential of PLAP-1 as a therapeutic target for periodontal diseases.

    DOI: 10.3390/ijms242115989

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  • Procyanidin B2 enhances anti-inflammatory responses of periodontal ligament cells by inhibiting the dominant negative pro-inflammatory isoforms of peroxisome proliferator-activated receptor γ Reviewed

    Tadahiro Yamamoto, Hang Yuan, Shigeki Suzuki, Eiji Nemoto, Masahiro Saito, Satoru Yamada

    Journal of Dental Sciences   2023.10

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

    DOI: 10.1016/j.jds.2023.09.027

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  • Public RNA-seq data-based identification and functional analyses reveal that MXRA5 retains proliferative and migratory abilities of dental pulp stem cells Reviewed

    Kazuma Yoshida, Shigeki Suzuki, Hang Yuan, Akiko Sato, Shizu Hirata-Tsuchiya, Masahiro Saito, Satoru Yamada, Hideki Shiba

    Scientific Reports   13 ( 1 )   2023.9

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    Authorship:Lead author, Corresponding author   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Abstract

    Dental pulp stem cells (DPSC) usually remain quiescent in the dental pulp tissue; however, once the dental pulp tissue is injured, DPSCs potently proliferate and migrate into the injury microenvironment and contribute to immuno-modulation and tissue repair. However, the key molecules that physiologically support the potent proliferation and migration of DPSCs have not been revealed. In this study, we searched publicly available transcriptome raw data sets, which contain comparable (i.e., equivalently cultured) DPSC and mesenchymal stem cell data. Three data sets were extracted from the Gene Expression Omnibus database and then processed and analyzed. MXRA5 was identified as the predominant DPSC-enriched gene associated with the extracellular matrix. MXRA5 is detected in human dental pulp tissues. Loss of MXRA5 drastically decreases the proliferation and migration of DSPCs, concomitantly with reduced expression of the genes associated with the cell cycle and microtubules. In addition to the known full-length isoform of MXRA5, a novel splice variant of MXRA5 was cloned in DPSCs. Recombinant MXRA5 coded by the novel splice variant potently induced the haptotaxis migration of DPSCs, which was inhibited by microtubule inhibitors. Collectively, MXRA5 is a key extracellular matrix protein in dental pulp tissue for maintaining the proliferation and migration of DPSCs.

    DOI: 10.1038/s41598-023-42684-z

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    Other Link: https://www.nature.com/articles/s41598-023-42684-z

  • クロマチンアクセシビリティ解析による歯髄幹細胞分化における機能的転写因子/転写制御因子の探索 Reviewed

    Shigeki Suzuki, Ryu Hasegawa, Akiko Sato, Yoshino Daidouji, Karin Nagasaki, Eiji Nemoto, Satoru Yamada

    66 ( 3 )   179 - 191   2023.6

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    Authorship:Lead author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)  

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  • Pharmacological Activation of YAP/TAZ by Targeting LATS1/2 Enhances Periodontal Tissue Regeneration in a Murine Model Reviewed

    Akiko Sato, Shigeki Suzuki, Hang Yuan, Rahmad Fahreza, Xiuting Wang, Eiji Nemoto, Masahiro Saito, Satoru Yamada

    International Journal of Molecular Sciences   24 ( 2 )   2023.1

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    Due to their multi-differentiation potential, periodontal ligament fibroblasts (PDLF) play pivotal roles in periodontal tissue regeneration in vivo. Several in vitro studies have suggested that PDLFs can transmit mechanical stress into favorable basic cellular functions. However, the application of mechanical force for periodontal regeneration therapy is not expected to exhibit an effective prognosis since mechanical forces, such as traumatic occlusion, also exacerbate periodontal tissue degeneration and loss. Herein, we established a standardized murine periodontal regeneration model and evaluated the regeneration process associated with cementum remodeling. By administering a kinase inhibitor of YAP/TAZ suppressor molecules, such as large tumor suppressor homolog 1/2 (LATS1/2), we found that the activation of YAP/TAZ, a key downstream effector of mechanical signals, accelerated periodontal tissue regeneration due to the activation of PDLF cell proliferation. Mechanistically, among six kinds of MAP4Ks previously reported as upstream kinases that suppressed YAP/TAZ transcriptional activity through LATS1/2 in various types of cells, MAP4K4 was identified as the predominant MAP4K in PDLF and contributed to cell proliferation and differentiation depending on its kinase activity. Ultimately, pharmacological activation of YAP/TAZ by inhibiting upstream inhibitory kinase in PDLFs is a valuable strategy for improving the clinical outcomes of periodontal regeneration therapies.

    DOI: 10.3390/ijms24020970

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  • Epigenetics in susceptibility, progression, and diagnosis of periodontitis Invited Reviewed International journal

    Shigeki Suzuki, Satoru Yamada

    Japanese Dental Science Review   58   183 - 192   2022.11

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

    Periodontitis is characterized by irreversible destruction of periodontal tissue. At present, the accepted etiology of periodontitis is based on a three-factor theory including pathogenic bacteria, host factors, and acquired factors. Periodontitis development usually takes a decade or longer and is therefore called chronic periodontitis (CP). To search for genetic factors associated with CP, several genome-wide association study (GWAS) analyses were conducted; however, polymorphisms associated with CP have not been identified. Epigenetics, on the other hand, involves acquired transcriptional regulatory mechanisms due to reversibly altered chromatin accessibility. Epigenetic status is a condition specific to each tissue and cell, mostly determined by the responses of host cells to stimulations by local factors, like bacterial inflammation, and systemic factors such as nutrition status, metabolic diseases, and health conditions. Significantly, epigenetic status has been linked with the onset and progression of several acquired diseases. Thus, epigenetic factors in periodontal tissues are attractive targets for periodontitis diagnosis and treatments. In this review, we introduce accumulating evidence to reveal the epigenetic background effects related to periodontitis caused by genetic factors, systemic diseases, and local environmental factors, such as smoking, and clarify the underlying mechanisms by which epigenetic alteration influences the susceptibility of periodontitis.

    DOI: 10.1016/j.jdsr.2022.06.001

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  • Loss of IκBζ Drives Dentin Formation via Altered H3K4me3 Status Reviewed

    H. Yuan, S. Suzuki, H. Terui, S. Hirata-Tsuchiya, E. Nemoto, K. Yamasaki, M. Saito, H. Shiba, S. Aiba, S. Yamada

    Journal of Dental Research   101 ( 8 )   951 - 961   2022.7

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    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)   Publisher:SAGE Publications  

    Enforced enrichment of the active promoter marks trimethylation of histone H3 lysine 4 (H3K4me3) and acetylation of histone H3 lysine 27 (H3K27ac) by inhibiting histone demethylases and deacetylases is positively associated with hard tissue formation through the induction of osteo/odontogenic differentiation. However, the key endogenous epigenetic modulator of odontoblasts to regulate the expression of genes coding dentin extracellular matrix (ECM) proteins has not been identified. We focused on nuclear factor (NF)–κB inhibitor ζ (IκBζ), which was originally identified as the transcriptional regulator of NF-κB and recently regarded as the NF-κB–independent epigenetic modulator, and found that IκBζ null mice exhibit a thicker dentin width and narrower pulp chamber, with aged mice having more marked phenotypes. At 6 mo of age, dentin fluorescent labeling revealed significantly accelerated dentin synthesis in the incisors of IκBζ null mice. In the molars of IκBζ null mice, marked tertiary dentin formation adjacent to the pulp horn was observed. Mechanistically, the expression of COL1A2 and COL1A1 collagen genes increased more in the odontoblast-rich fraction of IκBζ null mice than in wild type in vivo, similar to human odontoblast-like cells transfected with small interfering RNA for IκBζ compared with cells transfected with control siRNA in vitro. Furthermore, the direct binding of IκBζ to the COL1A2 promoter suppressed COL1A2 expression and the local active chromatin status marked by H3K4me3. Based on whole-genome identification of H3K4me3 enrichment, ECM and ECM organization–related gene loci were selectively activated by the knockdown of IκBζ, which consistently resulted in the upregulation of these genes. Collectively, this study suggested that IκBζ is the key negative regulator of dentin formation in odontoblasts by inhibiting dentin ECM- and ECM organization–related gene expression through an altered local chromatin status marked by H3K4me3. Therefore, IκBζ is a potential target for epigenetically improving the clinical outcomes of dentin regeneration therapies such as pulp capping.

    DOI: 10.1177/00220345221075968

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    Other Link: http://journals.sagepub.com/doi/full-xml/10.1177/00220345221075968

  • Extracellular Vesicles Derived From Murine Cementoblasts Possess the Potential to Increase Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclastogenesis Reviewed International journal

    Rei Sato, Kentaro Maruyama, Eiji Nemoto, Yukihiko Sakisaka, Shigeki Suzuki, Jiajun Li, Kento Numazaki, Hiroyuki Tada, Satoru Yamada

    Frontiers in Physiology   13   825596 - 825596   2022.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Frontiers Media SA  

    Cementum resorption, unlike bone resorption, is clinically known to occur only with limited pathological stimuli, such as trauma, orthodontic forces, and large apical periodontitis; however, the molecular mechanisms that control osteoclast formation on the cementum surface remain unclear. In this study, we focused on extracellular vesicles (EVs) secreted by cementoblasts and analyzed their effects on osteoclast differentiation. EVs were extracted from the conditioned medium (CM) of the mouse cementoblast cell line OCCM-30. Transmission electron microscopy (TEM) analysis confirmed the presence of EVs with a diameter of approximately 50–200 nm. The effect of the EVs on osteoclast differentiation was examined using the mouse osteoclast progenitor cell line RAW 264.7 with recombinant receptor activator of nuclear factor (NF)-κB ligand (rRANKL) stimulation. EVs enhanced the formation of tartrate-resistant acid phosphatase (TRAP) activity-positive cells upon rRANKL stimulation. EVs also enhanced the induction of osteoclast-associated gene and protein expression in this condition, as determined by real-time PCR and Western blotting, respectively. On the other hand, no enhancing effect of EVs was observed without rRANKL stimulation. A Western blot analysis revealed no expression of receptor activator of NF-κB ligand (RANKL) in EVs themselves. The effect on rRANKL-induced osteoclast differentiation was examined using the CM of cementoblasts in terms of TRAP activity-positive cell formation and osteoclast-associated gene expression. The conditioned medium partly inhibited rRANKL-induced osteoclast differentiation and almost completely suppressed its enhancing effect by EVs. These results indicate that cementoblasts secreted EVs, which enhanced RANKL-induced osteoclast differentiation, and simultaneously produced soluble factors that neutralized this enhancing effect of EVs, implicating this balance in the regulation of cementum absorption. A more detailed understanding of this crosstalk between cementoblasts and osteoclasts will contribute to the development of new therapies for pathological root resorption.

    DOI: 10.3389/fphys.2022.825596

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  • Leucine rich amelogenin peptide prevents ovariectomy-induced bone loss in mice Reviewed

    Naoto Haruyama, Takayoshi Yamaza, Shigeki Suzuki, Bradford Hall, Andrew Cho, Carolyn W. Gibson, Ashok B. Kulkarni

    PLOS ONE   16 ( 11 )   e0259966 - e0259966   2021.11

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    Publishing type:Research paper (scientific journal)   Publisher:Public Library of Science (PLoS)  

    Amelogenins, major extra cellular matrix proteins of developing tooth enamel, are predominantly expressed by ameloblasts and play significant roles in the formation of enamel. Recently, amelogenin has been detected in various epithelial and mesenchymal tissues, implicating that it might have distinct functions in various tissues. We have previously reported that leucine rich amelogenin peptide (LRAP), one of the alternate splice forms of amelogenin, regulates receptor activator of NF-kappa B ligand (RANKL) expression in cementoblast/periodontal ligament cells, suggesting that the amelogenins, especially LRAP, might function as a signaling molecule in bone metabolism. The objective of this study was to identify and define LRAP functions in bone turnover. We engineered transgenic (TgLRAP) mice using a murine 2.3kb α1(I)-collagen promoter to drive expression of a transgene consisting of LRAP, an internal ribosome entry site (IRES) and enhanced green fluorescent protein (EGFP) to study functions of LRAP in bone formation and resorption. Calvarial cell cultures from the TgLRAP mice showed increased alkaline phosphatase (ALP) activity and increased formation of mineralized nodules compared to the cells derived from wild-type (WT) mice. The TgLRAP calvarial cells also showed an inhibitory effect on osteoclastogenesis <italic>in vitro</italic>. Gene expression comparison by quantitative polymerase chain reaction (Q-PCR) in calvarial cells indicated that bone formation makers such as <italic>Runx2</italic>, <italic>Alp</italic>, and <italic>osteocalcin</italic> were increased in TgLRAP compared to the WT cells. Meanwhile, <italic>Rankl</italic> expression was decreased in the TgLRAP cells <italic>in vitro</italic>. The ovariectomized (OVX) TgLRAP mice resisted bone loss induced by ovariectomy resulting in higher bone mineral density in comparison to OVX WT mice. The quantitative analysis of calcein intakes indicated that the ovariectomy resulted in increased bone formation in both WT and TgLRAP mice; OVX TgLRAP appeared to show the most remarkably increased bone formation. The parameters for bone resorption in tissue sections showed increased number of osteoclasts in OVX WT, but not in OVX TgLRAP over that of sham operated WT or TgLRAP mice, supporting the observed bone phenotypes in OVX mice. This is the first report identifying that LRAP, one of the amelogenin splice variants, affects bone turnover <italic>in vivo</italic>.

    DOI: 10.1371/journal.pone.0259966

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  • PPARγ-Induced Global H3K27 Acetylation Maintains Osteo/Cementogenic Abilities of Periodontal Ligament Fibroblasts Reviewed International journal

    Hang Yuan, Shigeki Suzuki, Shizu Hirata-Tsuchiya, Akiko Sato, Eiji Nemoto, Masahiro Saito, Hideki Shiba, Satoru Yamada

    International Journal of Molecular Sciences   22 ( 16 )   2021.8

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

    The periodontal ligament is a soft connective tissue embedded between the alveolar bone and cementum, the surface hard tissue of teeth. Periodontal ligament fibroblasts (PDLF) actively express osteo/cementogenic genes, which contribute to periodontal tissue homeostasis. However, the key factors maintaining the osteo/cementogenic abilities of PDLF remain unclear. We herein demonstrated that PPARγ was expressed by in vivo periodontal ligament tissue and its distribution pattern correlated with alkaline phosphate enzyme activity. The knockdown of PPARγ markedly reduced the osteo/cementogenic abilities of PDLF in vitro, whereas PPARγ agonists exerted the opposite effects. PPARγ was required to maintain the acetylation status of H3K9 and H3K27, active chromatin markers, and the supplementation of acetyl-CoA, a donor of histone acetylation, restored PPARγ knockdown-induced decreases in the osteo/cementogenic abilities of PDLF. An RNA-seq/ChIP-seq combined analysis identified four osteogenic transcripts, RUNX2, SULF2, RCAN2, and RGMA, in the PPARγ-dependent active chromatin region marked by H3K27ac. Furthermore, RUNX2-binding sites were selectively enriched in the PPARγ-dependent active chromatin region. Collectively, these results identified PPARγ as the key transcriptional factor maintaining the osteo/cementogenic abilities of PDLF and revealed that global H3K27ac modifications play a role in the comprehensive osteo/cementogenic transcriptional alterations mediated by PPARγ.

    DOI: 10.3390/ijms22168646

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  • Mouse Model of Loeys–Dietz Syndrome Shows Elevated Susceptibility to Periodontitis via Alterations in Transforming Growth Factor-Beta Signaling Reviewed

    Satoru Yamada, Kenichiro Tsushima, Masaki Kinoshita, Hiromi Sakashita, Tetsuhiro Kajikawa, Chiharu Fujihara, Hang Yuan, Shigeki Suzuki, Takayuki Morisaki, Shinya Murakami

    Frontiers in Physiology   12   2021.8

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    Publishing type:Research paper (scientific journal)   Publisher:Frontiers Media {SA}  

    <jats:p>Loeys–Dietz syndrome (LDS) is a syndromic connective tissue disorder caused by a heterozygous missense mutation in genes that encode transforming growth factor (TGF)-β receptor (<jats:italic>TGFBR</jats:italic>) <jats:italic>1</jats:italic> and <jats:italic>2</jats:italic>. We encountered a patient with LDS, who had severe periodontal tissue destruction indicative of aggressive periodontitis. The patient had a missense mutation in the glycine and serine-rich domain of <jats:italic>TGFBR1</jats:italic> exon 3. This G-to-T mutation at base 563 converted glycine to valine. We established an LDS model knock-in mouse that recapitulated the LDS phenotype. Homozygosity of the mutation caused embryonic lethality and heterozygous knock-in mice showed distorted and ruptured elastic fibers in the aorta at 24 weeks of age and died earlier than wildtype (WT) mice. We stimulated mouse embryonic fibroblasts (MEFs) from the knock-in mouse with TGF-β and examined their responses. The knock-in MEFs showed downregulated <jats:italic>Serpine 1</jats:italic> mRNA expression and phosphorylation of Smad2 to TGF-β compared with WT MEFs. To clarify the influence of TGF-β signaling abnormalities on the pathogenesis or progression of periodontitis, we performed pathomolecular analysis of the knock-in mouse. There were no structural differences in periodontal tissues between WT and LDS model mice at 6 or 24 weeks of age. Micro-computed tomography revealed no significant difference in alveolar bone resorption between WT and knock-in mice at 6 or 24 weeks of age. However, TGF-β-related gene expression was increased significantly in periodontal tissues of the knock-in mouse compared with WT mice. Next, we assessed a mouse periodontitis model in which periodontal bone loss was induced by oral inoculation with the bacterial strain <jats:italic>Porphyromonas gingivalis</jats:italic> W83. After inoculation, we collected alveolar bone and carried out morphometric analysis. <jats:italic>P. gingivalis</jats:italic>-induced alveolar bone loss was significantly greater in LDS model mice than in WT mice. Peritoneal macrophages isolated from <jats:italic>Tgfbr1<jats:sup><jats:italic>G</jats:italic>188V/+</jats:sup></jats:italic> mice showed upregulation of inflammatory cytokine mRNA expression induced by <jats:italic>P. gingivalis</jats:italic> lipopolysaccharide compared with WT macrophages. In this study, we established an LDS mouse model and demonstrated that LDS model mice had elevated susceptibility to <jats:italic>P. gingivalis</jats:italic>-induced periodontitis, probably through TGF-β signal dysfunction. This suggests that TGF-β signaling abnormalities accelerate the pathogenesis or progression of periodontitis.</jats:p>

    DOI: 10.3389/fphys.2021.715687

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  • DMP-1 promoter-associated antisense strand non-coding RNA, panRNA-DMP-1, physically associates with EGFR to repress EGF-induced squamous cell carcinoma migration Reviewed International journal

    Shigeki Suzuki, Hang Yuan, Shizu Hirata-Tsuchiya, Kazuma Yoshida, Akiko Sato, Eiji Nemoto, Hideki Shiba, Satoru Yamada

    Molecular and Cellular Biochemistry   476 ( 4 )   1673 - 1690   2021.4

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media {LLC}  

    Accumulating evidence suggests that specific non-coding RNAs exist in many types of malignant tissues, and are involved in cancer invasion and metastasis. However, little is known about the precise roles of non-coding RNAs in squamous cell carcinoma (SQCC) invasion and migration. Recently, the dentin matrix protein-1 (DMP-1) gene locus was identified as a transcriptionally active site in squamous cell carcinoma (SQCC) tissue and cells. However, it is unclear whether RNA associated with cell migration exist at the DMP-1 gene locus in SQCC cells. We identified a novel promoter-associated non-coding RNA in the antisense strand of DMP-1 gene locus, promoter-associated non-coding RNA (panRNA)-DMP-1, by the RACE method in SQCC cells and tissues, and characterized the functions of panRNA-DMP-1 in EGF-driven SQCC cell migration. The inhibition of endogenous panRNA-DMP-1 expression by specific siRNAs and exogenous over-expression of panRNA-DMP-1 resulted in increased and suppressed cellular migration toward EGF in SQCC cells, respectively, and nuclear expression of panRNA-DMP-1 was induced by EGF stimulation. Mechanistically, suppression of panRNA-DMP-1 expression increased EGFR nuclear localization upon EGF treatment and nuclear panRNA-DMP-1 physically interacted with EGFR, which was confirmed by RNA immunoprecipitation assay using a bacteriophage-delivered PP7 RNA labeling system. Furthermore, co-immunoprecipitation assay revealed that suppression of panRNA-DMP-1 stabilized EGFR interaction with STAT3, a known co-transcription factors of EGFR, to induce migratory properties in many cancer cells. Based on these findings, panRNA-DMP-1 is an EGFR-associating RNA that inhibits the EGF-induced migratory properties of SQCC possibly by regulating EGFR nuclear localization and EGFR binding to STAT3.

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  • Inhibition of the CXCL9-CXCR3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation Reviewed International journal

    Tatsuya Hasegawa, V. Venkata Suresh, Yoshio Yahata, Masato Nakano, Shigeto Suzuki, Shigeki Suzuki, Satoru Yamada, Hideki Kitaura, Itaru Mizoguchi, Yuichiro Noiri, Keisuke Handa, Masahiro Saito

    Scientific Reports   11 ( 1 )   2613 - 2613   2021.1

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    <title>Abstract</title>Apical periodontitis (AP) is an acute or chronic inflammatory disease caused by complex interactions between infected root canal and host immune system. It results in the induction of inflammatory mediators such as chemokines and cytokines leading to periapical tissue destruction. To understand the molecular pathogenesis of AP, we have investigated inflammatory-related genes that regulate AP development. We found here that macrophage-derived CXCL9, which acts through CXCR3, is recruited by progressed AP. The inhibition of CXCL9 by a CXCR3 antagonist reduced the lesion size in a mouse AP model with decreasing IL-1β, IL-6 and TNFα expression. The treatment of peritoneal macrophages with CXCL9 and LPS induced the transmigration and upregulation of osteoclastogenic cytokines such as IL-1β, IL-6 and matrix metalloprotease 2, a marker of activated macrophages. This suggests that the CXCL9-CXCR3 axis plays a crucial role in the development of AP, mediated by the migration and activation of macrophages for periapical tissue destruction. Our data thus show that CXCL9 regulates the functions of macrophages which contribute to AP pathogenesis, and that blocking CXCL9 suppresses AP progression. Knowledge of the principal factors involved in the progression of AP, and the identification of related inflammatory markers, may help to establish new therapeutic strategies.

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  • Surgical Sealing of Laterally Localized Accessory Root Canal with Resin Containing S-PRG Filler in Combination with Non-Surgical Endodontic Treatment: A Case Report Reviewed International journal

    Shizu Hirata-Tsuchiya, Shigeki Suzuki, Takashi Nakamoto, Naoya Kakimoto, Satoru Yamada, Hideki Shiba

    Dentistry Journal   8 ( 4 )   131 - 131   2020.11

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    The spread of root canal infection to surrounding periodontal tissue through accessory root canals reduces the success rate of endodontic treatment. In this case, cone-beam computed tomography revealed a lesion (4 mm from the apex) resulting from an accessory root canal of the maxillary left central incisor. First, non-surgical endodontic treatment was conducted but the sinus tract remained. Surgical preparation of the root cavity was then conducted to remove potentially infected dentin surrounding the accessory root canal. The cavity was filled and the foramen was sealed with resin containing bioactive surface pre-reacted glass (S-PRG) filler. The photopolymerized resin was then contoured and polished. In combination with subsequent supportive non-surgical endodontic treatment, a good clinical outcome with the disappearance of the sinus tract and clinical symptoms such as discomfort and pressure pain and the regeneration of the alveolar bone hanging over the cavity was obtained. In this case, the good clinical outcome may have been due to the dentin-adhesive property and durability of the pre-adhesive system and composite resin. The better biocompatibility of S-PRG fillers presumably facilitated periodontal tissue healing.

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  • A small nuclear acidic protein (MTI-II, Zn2+-binding protein, parathymosin) attenuates TNF-α inhibition of BMP-induced osteogenesis by enhancing accessibility of the Smad4-NF-κB p65 complex to Smad binding element Reviewed International journal

    Shizu Hirata-Tsuchiya, Shigeki Suzuki, Kazuki Okamoto, Noriko Saito, Hang Yuan, Satoru Yamada, Eijiro Jimi, Hideki Shiba, Chiaki Kitamura

    Molecular and Cellular Biochemistry   469 ( 1-2 )   133 - 142   2020.6

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    Pro-inflammatory cytokines prevent bone regeneration in vivo and activation of nuclear factor-κB (NF-κB) signaling has been proposed to lead to suppression of bone morphogenetic protein (BMP)-induced osteogenesis via direct binding of p65 to Smad4 in vitro. Application of a small nuclear acidic protein (MTI-II) and its delivered peptide, MPAID (MTI-II peptide anti-inflammatory drug) has been described to elicit therapeutic potential via strong anti-inflammatory action following the physical association of MTI-II and MPAID with p65. However, it is unclear whether MTI-II attenuates tumor necrosis factor (TNF)-α inhibition of BMP-induced osteogenesis. Herein, we found that TNF-α-mediated suppression of responses associated with BMP4-induced osteogenesis, including expression of the osteocalcin encoding gene Ocn, Smad binding element (SBE)-dependent luciferase activity, alkaline phosphatase activity, and alizarin red S staining were largely restored by MTI-II and MPAID in MC3T3-E1 cells. Mechanistically, MTI-II and MPAID did not inhibit nuclear translocation of p65 or disassociate Smad4 from p65. Further, results from chromatin immunoprecipitation (ChIP) analyses revealed that Smad4 enrichment in cells over-expressing MTI-II and treated with TNF-α was equivalent to that in cells without TNF-α treatment. Alternatively, Smad4 enrichment was considerably decreased following TNF-α treatment in control cells. Moreover, p65 enrichment in the Id-1 promoter SBE was detected only when cells over-expressing MTI-II were stimulated with TNF-α. Overall, our study concludes that MTI-II restored TNF-α-inhibited suppression of BMP-Smad-induced osteogenic differentiation by enhancing accessibility of the Smad4-p65 complex to the SBE rather than by liberating Smad4 from p65.

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  • Dentin phosphoprotein inhibits lipopolysaccharide-induced macrophage activation independent of its serine/aspartic acid-rich repeats Reviewed

    Jun Nakanishi, Shigeki Suzuki, Kazuma Yoshida, Shizu Hirata-Tsuchiya, Naoto Haruyama, Satoru Yamada, Hideki Shiba

    Archives of Oral Biology   110   2020.2

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    © 2019 Elsevier Ltd Objective: The objective of this study was to investigate the effects of dentin phosphoprotein (DPP) on lipopolysaccharide-induced inflammatory responses of macrophages in vitro. Design: Wildtype and mutant recombinant dentin phosphoprotein (rDPP) proteins were generated using a mammalian expression system. Macrophages, phorbol 12-myristate 13-acetate-differentiated THP-1 cells, were stimulated with lipopolysaccharide in the absence or presence of rDPP proteins. After the 24-hr incubation, the inflammatory gene expression levels were examined by quantitative reverse-transcription polymerase chain reaction and the amount of secreted TNF-α protein was evaluated by enzyme-linked immunosorbent assay. Furthermore, the subcellular localization of exogenously added rDPP was examined by immunocytochemistry, and the direct binding of rDPP to lipopolysaccharide was quantified by solid-phase binding assay. Results: rDPP dose-dependently reduced the expression of lipopolysaccharide-induced inflammatory genes, such as TNFα, IL-1β, and IL-8, and TNF-α protein secretion from the macrophages. Furthermore, mutant rDPP having a shortened serine/aspartic acid-rich repeats (SDrr) was also able to inhibit lipopolysaccharide-induced inflammatory responses of macrophages. rDPP was localized adjacent to the cellular membrane rather than in the cytoplasm, and rDPP was able to bind to lipopolysaccharide. These results suggested that rDPP inhibited lipopolysaccharide-induced inflammatory responses by binding to lipopolysaccharide. Conclusions: In addition to the well-known functions of DPP for dentin mineralization that depend on the SDrr, we demonstrated that DPP possesses anti-inflammatory effects on lipopolysaccharide-stimulated macrophages that are independent of the SDrr.

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  • Dental pulp cell-derived powerful inducer of TNF-α comprises PKR containing stress granule rich microvesicles Reviewed International journal

    Shigeki Suzuki

    Scientific Reports   9 ( 1 )   3825 - 3825   2019.12

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    It is well known that dental pulp tissue can evoke some of the most severe acute inflammation observed in the human body. We found that dental pulp cells secrete a factor that induces tumor necrosis factor-α production from macrophages, and designated this factor, dental pulp cell-derived powerful inducer of TNF-α (DPIT). DPIT was induced in dental pulp cells and transported to recipient cells via microvesicles. Treatment of dental pulp cells with a PKR inhibitor markedly suppressed DPIT activity, and weak interferon signals were constitutively activated inside the cells. In recipient macrophages, stimulation with DPIT-containing supernatants from pulp cells resulted in activation of both nuclear factor-κB and MAP kinases like JNK and p38. Proteomics analyses revealed that many stress granule-related proteins were present in supernatants from dental pulp cells as well as microvesicle marker proteins like GAPDH, β-actin, HSPA8, HSPB1, HSPE1, and HSPD1. Furthermore, giant molecule AHNAK and PKR were detected in microvesicles derived from dental pulp cells, and gene silencing of AHNAK in dental pulp cells led to reduced DPIT activity. Thus, it appeared that the core protein of DPIT was PKR, and that PKR was maintained in an active state in stress granule aggregates with AHNAK and transported via microvesicles. The activity of DPIT for TNF-α induction was far superior to that of gram-negative bacterial endotoxin. Therefore, we, report for the first time, that active PKR is transported via microvesicles as stress granule aggregates and induces powerful inflammatory signals in macrophages.

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  • Heparin-LL37 complexes are less cytotoxic for human dental pulp cells and have undiminished antimicrobial and LPS-neutralizing abilities. Reviewed

    Yoshida K, Suzuki S, Kawada-Matsuo M, Nakanishi J, Hirata-Tsuchiya S, Komatsuzawa H, Yamada S, Shiba H

    International Endodontic Journal   52 ( 9 )   1327 - 1343   2019.9

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    © 2019 International Endodontic Journal. Published by John Wiley & Sons Ltd Aim: To investigate whether glycosaminoglycans (GAGs) binding to high-dose LL37 eliminates its cytotoxicity to dental pulp cells (hDPCs) whilst retaining undiminished antimicrobial and LPS-neutralizing abilities. Methodology: hDPCs were stimulated with varying concentrations of LL37, and their cell viability was analysed by MTT. Then, high-dose LL37 (10 μmol L−1) was bound to varying concentrations of three GAGs, heparin, chondroitin sulphate and hyaluronic acid, and their cytotoxic effects on hDPCs and antimicrobial effects were evaluated and compared. Furthermore, the LPS-neutralizing ability of heparin (5 μg mL−1)–LL37 (10 μmol L−1) complexes, which were found to be less cytotoxic for hDPCs with undiminished antimicrobial ability, was investigated. Statistical analysis was performed using one-way analysis of variance (anova), followed by Dunnett's test. P values below 0.05 were considered significant. Results: LL37 significantly reduced the cell viability of hDPCs in a dose-dependent manner (P < 0.01). LL37 (10 μmol L−1) binding to heparin within a limited concentration range (2~6 μg mL−1) eliminated the cytotoxicity for hDPCs (P < 0.01) whilst exerting potent antimicrobial effects against Streptococcus mutans, Streptococcus sobrinus, Streptococcus salivarius, Aggegatibacter actinomycetemcomitans and Escherichia coli. LL37 (10 μmol L−1) binding to chondroitin sulphate exhibited similar functions (P < 0.01); however, the effective chondroitin sulphate concentration was highly restricted (3 μg mL−1). LL37 (10 μmol L−1) binding to hyaluronic acid was unable to abrogate the cytotoxicity of LL37 even at higher concentrations (10 and 100 μg mL−1). Moreover, exogenous addition of LPS dose-dependently reduced the amount of LL37 precipitated with the heparin–LL37 agarose beads (P < 0.01), and the released LL37 simultaneously neutralized the pro-inflammatory ability of LPS in macrophages (P < 0.01). Conclusions: Heparin–LL37 complexes generated at suitable concentration ratios are easy to make, are less cytotoxic and are broad-range antimicrobial materials that can neutralize LPS by providing LL37 in accordance with the amount of free LPS. They may be a potential treatment to save dental pulp tissue from the acute inflammation exacerbated by invading bacteria and the LPS they release.

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  • Cyclic Stretch Force Induces Periodontal Ligament Cells to Secrete Exosomes That Suppress IL-1β Production Through the Inhibition of the NF-κB Signaling Pathway in Macrophages Reviewed International journal

    Shigeki Suzuki

    Frontiers in Immunology   10   1310 - 1310   2019.6

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    In the oral mechanical environment, periodontal ligament cells (PDL cells) contribute to maintaining periodontal tissue homeostasis. Recent studies showed that exosomes, which are small vesicles secreted by various types of cells, play a pivotal role in cell-to-cell communication in biological processes. We examined the secretion of exosomes from PDL cells stimulated with cyclic stretch and their role in the inflammatory response of macrophages using the human macrophage cell line THP-1 and human primary monocytes/macrophages. We prepared supernatants from human PDL cells (PDL-sup) stimulated with cyclic stretch. The treatment of macrophages with PDL-sup, but not PDL-sup from unstimulated PDL cells, inhibited the production of IL-1β in LPS/nigericin-stimulated macrophages. The pretreatment of PDL cells with GW4869, an inhibitor of exosome secretion, or siRNA for Rab27B, which controls exosome secretion, abrogated the inhibitory effects of PDL-sup. A transmission electron microscopy analysis demonstrated the existence of exosomes with diameters ranging between 30 and 100 nm in PDL-sup, suggesting that exosomes in PDL-sup contribute to this inhibition. An immunofluorescence microscopy analysis revealed that exosomes labeled with PKH67, a fluorescent dye, were incorporated by macrophages as early as 2 h after the addition of exosomes. Purified exosomes inhibited IL-1β production in LPS/nigericin-stimulated macrophages and the nuclear translocation of NF-κB as well as NF-κB p65 DNA-binding activity in LPS-stimulated macrophages, suggesting that exosomes suppress IL-1β production by inhibiting the NF-κB signaling pathway. Our results indicate that PDL cells in mechanical environments contribute to the maintenance of periodontal immune/inflammatory homeostasis by releasing exosomes.

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  • 非翻訳長鎖RNAによるエピジェネティクスな遺伝子発現調節機構と歯周炎感受性との関連性 Invited Reviewed

    鈴木 茂樹, 袁 航, 栗田 真夏, 山田 聡

    日本歯周病学会会誌   61 ( 1 )   1 - 8   2019.3

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    非翻訳長鎖RNA(IncRNA)はエピジェネティクスな遺伝子発現調節機構を担う主要な制御因子であると認識されてきている。炎症性疾患では特徴的なIncRNAが同定されており、歯周炎においてもいくつかの歯周炎関連遺伝子座を近傍または遠隔に制御するIncRNAの存在が推定される。IncRNAと歯周炎、歯周組織恒常性維持責任遺伝子座であるSIB-LINGs、unspliced DMP-1による近傍遺伝子発現制御について概説した。

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  • Genome-wide identification of chromatin-enriched RNA reveals that unspliced dentin matrix protein-1 mRNA regulates cell proliferation in squamous cell carcinoma Reviewed

    Shigeki Suzuki, Hiroaki Hoshino, Kazuma Yoshida, Jun Nakanishi, Shizu Tsuchiya-Hirata, Seiji Kobuke, Naoto Haruyama, Fusanori Nishimura, Hideki Shiba

    Biochemical and Biophysical Research Communications   495 ( 3 )   2303 - 2309   2018.1

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    © 2017 Elsevier Inc. Chromatin-enriched noncoding RNAs (ncRNAs) have emerged as key molecules in epigenetic processes by interacting with chromatin-associated proteins. Recently, protein-coding mRNA genes have been reported to be chromatin-tethered, similar with ncRNA. However, very little is known about whether chromatin-enriched mRNA is involved in the chromatin modification process. Here, we comprehensively examined chromatin-enriched RNA in squamous cell carcinoma (SQCC) cells by RNA subcellular localization analysis, which was a combination of RNA fractionation and RNA-seq. We identified 11 mRNAs as highly chromatin-enriched RNAs. Among these, we focused on the dentin matrix protein-1 (DMP-1) gene because its expression in SQCC cells has not been reported. Furthermore, we clarified that DMP-1 mRNA was retained in chromatin in its unspliced form in SQCC in vitro and in vivo. As the inhibition of the unspliced DMP-1 mRNA (unspDMP-1) expression resulted in decreased cellular proliferation in SQCC cells, we performed ChIP-qPCR to identify cell cycle-related genes whose expression was epigenetically modified by unspDMP-1, and found that the CDKN1B promoter became active in SQCC cells by inhibiting unspDMP-1 expression. This result was further validated by the increased CDKN1B gene expression in the cells treated with siRNA for unspDMP-1 and by restoration of the decreased cellular proliferation rate by simultaneously inhibiting CDKN1B expression in SQCC cells. Further, to examine whether unspDMP-1 was able to associate with the CDKN1B promoter region, SQCC cells stably expressing PP7-mCherry fusion protein were transiently transfected with the unspDMP-1 fused to 24 repeats of the PP7 RNA stem loop (unspDMP-1-24xPP7) and we found that unspDMP-1-24xPP7 was efficiently precipitated with the antibody against mCherry and was significantly enriched in the CDKN1B promoter region. Thus, unspDMP-1 is a novel chromatin-enriched RNA that epigenetically regulates cellular proliferation of SQCC.

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  • Epicatechin downregulates adipose tissue CCL19 expression and thereby ameliorates diet-induced obesity and insulin resistance Reviewed

    T. Sano, S. Nagayasu, S. Suzuki, M. Iwashita, A. Yamashita, T. Shinjo, T. Sanui, A. Kushiyama, T. Kanematsu, T. Asano, F. Nishimura

    NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES   27 ( 3 )   249 - 259   2017.3

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    Background and aims: Epicatechin (EC) intake has been suggested to be beneficial for the prevention of cardiovascular disorders, and it is well known that adipose tissue inflammation is one of the major risk factors for coronary heart diseases. The purpose of the present study was to determine the in vitro and in vivo effects of EC on adipose tissue inflammation and obesity.
    Methods and results: DNA microarray analysis was performed to evaluate the effects of EC on gene expression in adipocytes co-cultured with bacterial endotoxin-stimulated macrophages. To determine the in vivo effects of the catechin, C57BL/6 mice were fed either a high-fat diet (HFD) or HFD combined with EC, and metabolic changes were observed EC suppressed the expression of many inflammatory genes in the adipocytes co-cultured with endotoxinstimulated macrophages. Specifically, EC markedly suppressed chemokine (C-C motif) ligand 19 (CCL19) expression. The target cell of EC appeared to macrophages. The in vivo study indicated that mice fed the EC-supplemented HFD were protected from diet-induced obesity and insulin resistance. Accordingly, the expression levels of genes associated with inflammation in adipose tissue and in the liver were downregulated in this group of mice.
    Conclusions: EC exerts beneficial effects for the prevention of adipose tissue inflammation and insulin resistance. Since we previously reported that mice deficient in the CCL19 receptor were protected from diet-induced obesity and insulin resistance, it can be concluded that the beneficial effects of EC could be mediated, at least in part, by marked suppression of CCL19 expression. (C) 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

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  • Dentin sialophosphoprotein is a potentially latent bioactive protein in dentin Invited Reviewed

    Shigeki Suzuki, Jun Nakanishi, Kazuma Yoshida, Hideki Shiba

    Journal of Oral Biosciences   58 ( 4 )   134 - 142   2016.11

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    Background Dentin sialophosphoprotein (DSPP) belongs to the family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs), which share common biochemical features such as an arginine-glycine-aspartic acid (RGD) integrin-binding site. However, amino acid sequence analyses suggest that DSPP has lost some common features, but acquired other unique features, such as repeat sequences of serine-serine-aspartic acid (SDrr) that are not observed in other SIBLINGs proteins. Highlight We review the biochemical features of DSPP using genetically modified mice and proteomic analyses. DSPP of some species lack the RGD sites unlike other SIBLING proteins such as dentin matrix protein-1 (DMP-1) and bone sialoprotein (BSP). We previously identified that mouse and human RGD domains in DSPP required the cleavage of an Ala-Ser peptide bond, next to the RGD domains, to become active. Other species such as bovine, sheep, and bears, possess a Thr-Ser bond next to the RGD domain, which is intrinsically unable to sequester the ability of the RGD domain. To predict the functional importance of certain proteins/domains based on evolutionary conservation rates, the RGD domain of DSPP did not appear to have pivotal roles compared to other SIBLINGs. However, upon investigating the peptide bond next to the RGD domains of DSPP in 37 species, we found most catarrhini, in which humans are classified, possess the Ala-Ser bond. Conclusion The functions of DSPP for integrin-mediated signaling possibly arize from the proteolytic cleavage of the peptide bonds close to the RGD domain and induce reactionary dentinogenesis in vivo.

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  • N-terminal Dentin Sialoprotein fragment induces type I collagen production and upregulates dentinogenesis marker expression in osteoblasts Reviewed

    Jaha, H., Husein, D., Ohyama, Y., Xu, D., Suzuki, S., Huang, G.T.-J., Mochida, Y.

    Biochemistry and Biophysics Reports   6   190 - 196   2016.6

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  • Relationship between length variations in Ser/Asp-rich repeats in phosphophoryn and in vitro precipitation of calcium phosphate Reviewed

    Seiji Kobuke, Shigeki Suzuki, Hiroaki Hoshino, Naoto Haruyama, Fusanori Nishimura, Hideki Shiba

    ARCHIVES OF ORAL BIOLOGY   60 ( 9 )   1263 - 1272   2015.9

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    Objective: Phosphophoryn (PP) is generated from the proteolytic cleavage of dentin sialophosphoprotein (DSPP). PP which contains tandem serine/asparatic acid rich repeats (SDrr) is known to enhance dentin mineralization. The nucleotide sequences coding SDrr are identified in the DSPP genes of toothed animals and the length variations of SDrr between intra- and inter-species have been reported. However, it remains unknown about the relationship between the length variations in SDrr and the functions of PP in matrix mineralization.
    Design: By utilizing a mammalian expression system, we generated several recombinant PP proteins (rPP) containing SDrr of different lengths and analyzed their effects on the precipitation of calcium phosphate with an in vitro gel diffusion system.
    Results: rPP-Delta 37.6 SDrr and rPP-Delta 63.5 SDrr, which possessed shortened SDrr that accounted for 62.4 and 36.5% the length of SDrr in full-length rPP (rPP-full), respectively, induced the precipitation of calcium phosphate similar to that of rPP-full at the same molar concentration, whereas rPP-Delta SDrr, in which SDrr were flipped, did not. Furthermore, rPP-Delta 63.5 SDrr significantly increased the accumulation of calcium compared with rPP-full at adjusted concentrations so that the same amounts of SDrr were embedded. The results of an ELISA analysis indicated that the amounts of rPP-Delta 37.6 SDrr and rPP-Delta 63.5 SDrr secreted from transfected cells were 5.2- and 7.1-fold greater than that of rPP-full, respectively.
    Conclusions: The generated rPP-Delta 63.5 SDrr which can be substituted for rPP-full may be a candidate for a therapeutic molecule to facilitate hard tissue generation such as reparative dentin formation. (C) 2015 Elsevier Ltd. All rights reserved.

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  • Wnt Acts as a Prosurvival Signal to Enhance Dentin Regeneration Reviewed

    Daniel J. Hunter, Claire Bardet, Sylvain Mouraret, Bo Liu, Gurpreet Singh, Jeremy Sadoine, Girija Dhamdhere, Andrew Smith, Xuan Vinh Tran, Adrienne Joy, Scott Rooker, Shigeki Suzuki, Annukka Vuorinen, Susanna Miettinen, Catherine Chaussain, Jill A. Helms

    JOURNAL OF BONE AND MINERAL RESEARCH   30 ( 7 )   1150 - 1159   2015.7

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    Wnt proteins are lipid-modified, short-range signals that control stem cell self-renewal and tissue regeneration. We identified a population of Wnt responsive cells in the pulp cavity, characterized their function, and then created a pulp injury. The repair response was evaluated over time using molecular, cellular, and quantitative assays. We tested how healing was impacted by wound environments in which Wnt signaling was amplified. We found that a Wnt-amplified environment was associated with superior pulp healing. Although cell death was still rampant, the number of cells undergoing apoptosis was significantly reduced. This resulted in significantly better survival of injured pulp cells, and resulted in the formation of more tertiary dentin. We engineered a liposome-reconstituted form of WNT3A then tested whether this biomimetic compound could activate cells in the injured tooth pulp and stimulate dentin regeneration. Pulp cells responded to the elevated Wnt stimulus by differentiating into secretory odontoblasts. Thus, transiently amplifying the body's natural Wnt response resulted in improved pulp vitality. These data have direct clinical implications for treating dental caries, the most prevalent disease affecting mankind. (c) 2015 American Society for Bone and Mineral Research.

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  • Adhesive and Migratory Effects of Phosphophoryn Are Modulated by Flanking Peptides of the Integrin Binding Motif Reviewed

    Shigeki Suzuki, Seiji Kobuke, Naoto Haruyama, Hiroaki Hoshino, Ashok B. Kulkarni, Fusanori Nishimura

    PLoS ONE   9 ( 11 )   e112490 - e112490   2014.11

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    Phosphophoryn (PP) is generated from the proteolytic cleavage of dentin sialophosphoprotein (DSPP). Gene duplications in the ancestor dentin matrix protein-1 (DMP-1) genomic sequence created the DSPP gene in toothed animals. PP and DMP-1 are phosphorylated extracellular matrix proteins that belong to the family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs). Many SIBLING members have been shown to evoke various cell responses through the integrinbinding Arg-Gly-Asp (RGD) domain; however, the RGD-dependent function of PP is not yet fully understood. We demonstrated that recombinant PP did not exhibit any obvious cell adhesion ability, whereas the simultaneously purified recombinant DMP-1 did. A cell adhesion inhibitory analysis was performed by pre-incubating human osteosarcoma MG63 cells with various PP peptides before seeding onto vitronectin. The results obtained revealed that the incorporation of more than one amino acid on both sides of the PP-RGD domain was unable to inhibit the adhesion of MG63 cells onto vitronectin. Furthermore, the inhibitory activity of a peptide containing the PP-RGD domain with an open carboxyl-terminal side (H-463SDESDTNSESANESGSRGDA482-OH) was more potent than that of a peptide containing the RGD domain with an open amino-terminal side (H-478SRGDASYTSDESSDDDNDSDSH499-OH). This phenomenon was supported by the potent cell adhesion and migration abilities of the recombinant truncated PP, which terminated with Ala482. Furthermore, various point mutations in Ala482 and/or Ser483 converted recombinant PP into cell-adhesive proteins. Therefore, we concluded that the Ala482-Ser483 flanking sequence, which was detected in primates and mice, was the key peptide bond that allowed the PPRGD domain to be sequestered. The differential abilities of PP and DMP-1 to act on integrin imply that DSPP was duplicated from DMP-1 to serve as a crucial extracellular protein for tooth development rather than as an integrin-mediated signaling molecule.

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  • The inflammation–lipocalin 2 axis may contribute to the development of chronic kidney disease Reviewed

    Atsushi Hashikata, Akiko Yamashita, Shigeki Suzuki, Shintaro Nagayasu, Takanori Shinjo, Ataru Taniguchi, Mitsuo Fukushima, Yoshikatsu Nakai, Kazuko Nin, Naoya Watanabe, Tomoichiro Asano, Yoshimitsu Abiko, Akifumi Kushiyama, Shoichiro Nagasaka, Fusanori Nishimura

    Nephrology Dialysis Transplantation   29 ( 3 )   611 - 618   2014.3

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    BackgroundChronic kidney disease (CKD) is an important risk factor for coronary heart disease, and previous studies indicated the involvement of low-grade inflammation in the pathogenesis of CKD.MethodsThe study was designed to (i) identify and confirm genes and their products upregulated in mesangial cells cocultured with endotoxin-stimulated macrophages and (ii) determine the clinical relevance of genes and proteins upregulated in mesangial cells under inflammatory conditions by an epidemiological approach.ResultsDNA microarray analysis revealed upregulated expression of many genes and their products including several cytokines and chemokines, as well as the inflammatory marker, lipocalin 2 gene. The gene expression and protein upregulation of lipocalin 2 were synergistically affected by endotoxin and tumor necrosis factor (TNF)-α stimulation. In human studies, lipocalin 2 level was significantly associated with creatinine (r = 0.419, P < 0.001) and negatively associated with eGFR (r = -0.365, P < 0.001). Multiple logistic regression analysis revealed a significant association between lipocalin 2 and soluble tumor necrosis factor receptor 2 (sTNF-R2), eGFR and uric acid in general subjects attending regular annual medical check-up (n = 420). When subjects with diabetes were excluded from the analysis, lipocalin 2 remained associated with sTNF-R2, eGFR and uric acid.ConclusionsSince an activated TNF system, as demonstrated by elevated sTNF-R2, and elevated uric acid were recently implicated in an elevated CKD risk, we conclude that inflammation could play an important role in the pathogenesis of CKD, and that lipocalin 2 is a potential universal marker for impaired kidney function. Furthermore, the results obtained by the current microarray analysis could improve the understanding of gene profiles associated with the pathophysiology of CKD under inflammatory conditions. © 2013 © The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

    DOI: 10.1093/ndt/gft449

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  • The Effects of Matrix Trioxide Aggregate (MTA) on the Adhesion, Migration and Apoptosis of Dental Pulp Cells Reviewed

    Shigeki SUZUKI, Shintaro NAGAYASU, Makoto ARAKAWA, Seiji KOBUKE, Hiroaki HOSHINO, Atsushi HASHIKATA, Tomotoku MOTOYAMA, Fusanori NISHIMURA

    Jpn J Conserv Dent   57 ( 6 )   547 - 554   2014

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    Purpose: Matrix trioxide aggregate (MTA) has been used for direct pulp-capping as well as perforation repair due to its potent ability to induce hard tissue regeneration. Pulp exposure, usually caused by tooth fracture and carious tooth treatment, involves the physical damage of pulp extracellular matrix. Therefore, when cells invade the damaged space from surrounding tissue, the existence of an adhesive substrate to aid cell proliferation and differentiation of invading cells is the key factor influencing the prognosis of pulp-capping treatment. In this study, we examined the effects of MTA on the adhesion, proliferation and apoptosis of human dental pulp cells (hDPCs) by comparison with composite resin (CR) and glass ionomer cement (GIC).<br> Materials and methods: Ninety-six-well plates were coated with MTA, CR, GIC and fibronectin. Cells were suspended in serum-free medium and then seeded onto coated wells. After 1.5-hr incubation at 37°C, the wells were rinsed to remove non-adherent cells. The number of adherent cells was quantified using the Cell Titer Glo Luminescent Cell Viability Assay Kit. For proliferation assay, these cells were seeded onto MTA, CR and GIC and attached cells were quantified. After 1.5-hr incubation, serum-free medium was replaced with 10% serum medium and cells were cultured onto these substrates for 72 hrs. The ability to induce apoptosis was evaluated by caspase 3/7 activity.<br> Result: MTA facilitated the adhesion of hDPCs, while CR and GIC did not. However, the adhesive effect of MTA was much weaker than that of fibronectin. hDPCs could attach onto MTA but not CR or GIC, even 72 hrs after seeding, although the number of attached cells gradually decreased during the culture period. These observations suggest that MTA could be used as a substrate for the adhesion, but not a scaffold for the proliferation, of hDPCs. A drastic increase of caspase 3/7 activity was observed when hDPCs were cultured onto CR and GIC. In contrast, MTA did not induce it.<br> Conclusions: Compared with CR and GIC, MTA is a good substrate for hDPC adhesion. These differential adhesive effects may be explained by the differential abilities for inducing pro-apoptotic signals in hDPCs. However, the effect of MTA as a cell adhesion substrate was much weaker than that of fibronectin. More importantly, MTA was unable to induce the proliferation of hDPCs on it. Thus, the co-addition of MTA with other adhesive and migratory proteins such as fibronectin may induce better wound healing and pulp tissue regeneration in vivo.

    DOI: 10.11471/shikahozon.57.547

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    Other Link: http://search.jamas.or.jp/link/ui/2015182150

  • Lessons Learned from Mouse Models of DSPP, DSP, and DPP Invited Reviewed

    Shigeki Suzuki

    Series Title: Frontiers Between Science and Clinic in Odontology Volume Title: Phosphorylated Extracellular Matrix Proteins of Bone and Dentin   10   221 - 230   2012.9

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    DOI: 10.2174/978160805465711202010221

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  • Dentin sialophosphoprotein and dentin matrix protein-1: Two highly phosphorylated proteins in mineralized tissues Reviewed

    Shigeki Suzuki, Naoto Haruyama, Fusanori Nishimura, Ashok B. Kulkarni

    ARCHIVES OF ORAL BIOLOGY   57 ( 9 )   1165 - 1175   2012.9

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    Dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1) are highly phosphorylated proteins that belong to the family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and are essential for proper development of hard tissues such as teeth and bones. In order to understand how they contribute to tissue organization, DSPP and DMP-1 have been analyzed for over a decade using both in vivo and in vitro techniques. Among the five SIBLINGs, the DSPP and DMP-1 genes are located next to each other and their gene and protein structures are most similar. In this review we examine the phenotypes of the genetically engineered mouse models of DSPP and DMP-1 and also introduce complementary in vitro studies into the molecular mechanisms underlying these phenotypes. DSPP affects the mineralization of dentin more profoundly than DMP-1. In contrast, DMP-1 significantly affects bone mineralization and importantly controls serum phosphate levels by regulating serum FGF-23 levels, whereas DSPP does not show any systemic effects. DMP-1 activates integrin signalling and is endocytosed into the cytoplasm whereupon it is translocated to the nucleus. In contrast, DSPP only activates integrin-dependent signalling. Thus it is now clear that both DSPP and DMP-1 contribute to hard tissue mineralization and the tissues affected by each are different presumably as a result of their different expression levels. In fact, in comparison with DMP-1, the functional analysis of cell signalling by DSPP remains relatively unexplored. (C) 2012 Elsevier LtdElsevier Ltd. All rights reserved.

    DOI: 10.1016/j.archoralbio.2012.03.005

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  • Smoking and adipose tissue inflammation suppress leptin expression in Japanese obese males: potential mechanism of resistance to weight loss among Japanese obese smokers Reviewed

    Shintaro Nagayasu, Shigeki Suzuki, Akiko Yamashita, Ataru Taniguchi, Mitsuo Fukushima, Yoshikatsu Nakai, Kazuko Nin, Naoya Watanabe, Shoichiro Nagasaka, Daisuke Yabe, Fusanori Nishimura

    TOBACCO INDUCED DISEASES   10 ( 10:3 )   2012.2

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    Background: The effect of smoking on leptin regulation is controversial. Smoking may induce low-grade inflammation. Recent series of studies indicated the critical role of macrophage migration in the establishment of adipose tissue inflammation. In this study, we aimed to see the effects of smoking and inflammation on leptin regulation both at cellular and epidemiological levels.
    Methods: We compared the concentration of inflammatory markers and serum leptin levels among Japanese male subjects. Additionally, leptin and intercellular adhesion molecule (ICAM) -1 gene expression was assessed in adipocytes co-cultured with or without macrophages in the presence or absence of nicotine and/or lipopolysaccharide (LPS).
    Results: In subjects with BMI below 25 kg/m(2), both WBC counts and soluble-ICAM-1 levels are significantly higher in smokers than in non-smokers. However, leptin concentration did not differ according to smoking status. However, in subjects with BMI over 25 kg/m(2), smokers exhibited significantly lower serum leptin level as well as higher WBC counts and s-ICAM-1 concentration as compared with non-smokers. Leptin gene expression was markedly suppressed in adipocytes co-cultured with macrophages than in adipocyte culture alone. Furthermore, nicotine further suppressed leptin gene expression. ICAM-1 gene expression was markedly up-regulated in adipocytes co-cultured with macrophages when stimulated with LPS.
    Conclusions: Adipose tissue inflammation appears to down-regulate leptin expression in adipose tissues. Nicotine further suppresses leptin expression. Thus, both smoking and inflammation may diminish leptin effect in obese subjects. Therefore, obese, but not normal weight, smokers might be more resistant to weight loss than nonsmokers.

    DOI: 10.1186/1617-9625-10-3

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  • A Method for Rapid Demineralization of Teeth and Bones Reviewed

    Shigeki Suzuki

    The Open Dentistry Journal   15 ( 4 )   223 - 229   2010.12

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    <jats:p>Tooth and bone specimen require extensive demineralization for careful analysis of cell morphology, as well as gene and protein expression levels. The LacZ gene, which encodes the ß-galactosidase enzyme, is often used as a reporter gene to study gene-structure function, tissue-specific expression by a promoter, cell lineage and fate. This reporter gene is particularly useful for analyzing the spatial and temporal gene expression pattern, by expressing the LacZ gene under the control of a promoter of interest. To analyze LacZ activity, and the expression of other genes and their protein products in teeth and bones, it is necessary to carry out a complete demineralization of the specimen before cutting sections. However, strong acids, such as formic acid used for tooth demineralization, destroy the activities of enzymes including those of ß-galactosidase. Therefore, most protocols currently use mild acids such as 0.1 M ethylene diamine tetra-acetic acid (EDTA) for demineralization of tooth and bone specimen, which require a longer period of treatment for complete demineralization. A method by which hard tissue specimens such as teeth and bones can be rapidly, but gently, decalcified is necessary to save time and effort. Here, we report a suitable method for rapid demineralization of mouse teeth in 0.1M EDTA at 42˚C without any loss of ß-galactosidase activity.</jats:p>

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  • Extracellular heat shock protein HSP90 beta secreted by MG63 osteosarcoma cells inhibits activation of latent TGF-beta 1 Reviewed

    Shigeki Suzuki, Ashok B. Kulkarni

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   398 ( 3 )   525 - 531   2010.7

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

    Transforming growth factor-beta 1 (TGF-beta 1) is secreted as a latent complex, which consists of latency-associated peptide (LAP) and the mature ligand. The release of the mature ligand from LAP usually occurs through conformational change of the latent complex and is therefore considered to be the first step in the activation of the TGF-beta signaling pathway. So far, factors such as heat, pH changes, and proteolytic cleavage are reportedly involved in this activation process, but the precise molecular mechanism is still far from clear. Identification and characterization of the cell surface proteins that bind to LAP are important to our understanding of the latent TGF-beta activation process. In this study, we have identified heat shock protein 90 beta (HSP90 beta) from the cell surface of the MG63 osteosarcoma cell line as a LAP binding protein. We have also found that MG63 cells secrete HSP90 beta into extracellular space which inhibits the activation of latent TGF-beta 1, and that there is a subsequent decrease in cell proliferation. TGF-beta 1 -mediated stimulation of MG63 cells resulted in the increased cell surface expression of HSP90 beta. Thus, extracellular HSP90 beta is a negative regulator for the activation of latent TGF-beta 1 modulating TGF-beta signaling in the extracellular domain. Published by Elsevier Inc.

    DOI: 10.1016/j.bbrc.2010.06.112

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  • 歯面コート材によるコーティングがもたらす歯質の脱灰抑制効果 Reviewed

    荒川真, 白井憲一, 鈴木茂樹, 本山直世, 山下明子, 峯岡茜, 藤井理史, 西村英紀

    日本歯科保存学雑誌   53   73 - 78   2010

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    DOI: 10.11471/shikahozon.53.73

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  • Dentin sialoprotein and dentin phosphoprotein have distinct roles in dentin mineralization Reviewed

    Shigeki Suzuki, Taduru Sreenath, Naoto Haruyama, Cherlita Honeycutt, Anita Terse, Andrew Cho, Thomas Kohler, Ralph Mueller, Michel Goldberg, Ashok B. Kulkarni

    MATRIX BIOLOGY   28 ( 4 )   221 - 229   2009.5

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    Dentin sialophosphoprotein (DSPP), a major non-collagenous matrix protein of odontoblasts, is proteolytically cleaved into dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Our previous studies revealed that DSPP null mice display a phenotype similar to human autosomal dominant dentinogenesis imperfecta. in which teeth have widened predentin and irregular dentin mineralization resulting in sporadic unmineralized areas in dentin and frequent pulp exposure. Earlier in vitro studies suggested that DPP, but not DSP, plays a significant role in initiation and maturation of dentin mineralization. However, the precise in vivo roles of DSP and DPP are far from clear. Here we report the generation of DPPcKO mice, in which only DSP is expressed in a DSPP null background, resulting in a conditional DPP knockout. DPPcKO teeth show a partial rescue of the DSPP null phenotype with the restored predentin width, an absence of irregular unmineralized areas in dentin, and less frequent pulp exposure. Micro-computed tomography (micro-CT) analysis of DPPcKO molars further confirmed this partial rescue with a significant recovery in the dentin volume, but not in the dentin mineral density. These results indicate distinct roles of DSP and DPP in dentin mineralization, with DSP regulating initiation of dentin mineralization, and DPP being involved in the maturation of mineralized dentin. Published by Elsevier B.V.

    DOI: 10.1016/j.matbio.2009.03.006

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  • Genetic evidence for key roles of decorin and biglycan in dentin mineralization Reviewed

    Naoto Haruyama, Taduru L. Sreenath, Shigeki Suzuki, Xiaomei Yao, Zhigang Wang, Yong Wang, Cherlita Honeycutt, Renato V. Iozzo, Marian F. Young, Ashok B. Kulkarni

    MATRIX BIOLOGY   28 ( 3 )   129 - 136   2009.4

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    Targeted disruption of the dentin sialophosphoprotein (DSPP) gene in the mice (Dspp(-/-)) results in dentin mineralization defects with enlarged predentin phenotype similar to human dentinogenesis imperfecta type Ill. Using DSPP/biglycan (Dspp(-/-)Bgn(-/0)) and DSPP/decorin (Dspp(-/-)Dcn(-/-)) double knockout mice, here we determined that the enlarged predentin layer in Dspp(-/-) teeth is rescued in the absence of decorin, but not in the absence of biglycan. However, Fourier transform infrared (FTIR) spectroscopy analysis reveals similar hypomineralization of dentin in both Dspp(-/-)Bgn(-/0) and Dspp(-/-)Dcn(-/-) teeth. Atomic force microscopy (AFM) analysis of collagen fibrils in dentin shows subtle differences in the collagen fibril morphology in these genotypes. The reduction of enlarged predentin in Dspp(-/-)Dcn(-/-) mice suggests that the elevated level of decorin in Dspp(-/-) predentin interferes with the mineralization process at the dentin mineralization front. On the other hand, the lack of DSPP and biglycan leads to the increased number of calcospherites in Dspp(-/-)Bgn(-/0) predentin, suggesting that a failure in coalescence of calcospherites was augmented in Dspp(-/-)Bgn(-/0) teeth as compared to Dspp(-/-) teeth. These findings indicate that normal expression of small leucine rich proteoglycans, such as biglycan and decorin, plays an important role in the highly orchestrated process of dentin mineralization. Published by Elsevier B.V.

    DOI: 10.1016/j.matbio.2009.01.005

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  • Synergistic Roles of Amelogenin and Ameloblastin Reviewed

    J. Hatakeyama, S. Fukumoto, T. Nakamura, N. Haruyama, S. Suzuki, Y. Hatakeyama, L. Shum, C. W. Gibson, Y. Yamada, A. B. Kulkarni

    JOURNAL OF DENTAL RESEARCH   88 ( 4 )   318 - 322   2009.4

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    Amelogenin and ameloblastin, the major enamel matrix proteins, are important for enamel mineralization. To identify their synergistic roles in enamel development, we generated Amel X(-/-)/Ambn(-/-) mice. These mice showed additional enamel defects in comparison with Amel X(-/-) or Ambn(-/-) mice. In 7-day-old Amel X(-/-)/Ambn(-/-) mice, not only was the ameloblast layer irregular and detached from the enamel surface, as in Ambn(-/-), but also, the enamel width was significantly reduced in the double-null mice as compared with Amel X(-/-) or Ambn(-/-) mice. Proteomic analysis of the double-null teeth revealed increased levels of RhoGDI (Arhgdia), a Rho-family-specific guanine nucleotide dissociation inhibitor, which is involved in important cellular processes, such as cell attachment. Both Amel X(-/-)/Ambn(-/-) mice and Ambn(-/-) mice displayed positive staining with RhoGDI antibody in the irregularly shaped ameloblasts detached from the matrix. Ameloblastin-regulated expression of RhoGDI suggests that Rho-mediated signaling pathway might play a role in enamel formation.

    DOI: 10.1177/0022034509334749

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Books

  • 臨床歯周病学

    山田 聡, 鈴木茂樹( Role: Contributor ,  5章 炎症反応・免疫反応p42-49)

    医歯薬出版株式会社  2020 

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  • 歯科再生医学

    鈴木茂樹, 山田聡( Role: Contributor ,  第2章05歯科再生医学にかかわるメカノトランスダクション)

    2019.4 

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  • 歯内療法のレベルアップ&ヒント

    鈴木茂樹, 柴秀樹( Role: Contributor ,  第11章02生物学的歯内療法)

    デンタルダイヤモンド社  2017 

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  • 保存修復学専門用語集 第2版 Glossary of Operative Dentistry 2017

    鈴木茂樹, 柴秀樹( Role: Contributor ,  601セレクティブエッチング: 54)

    医歯薬出版株式会社  2017 

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  • バイオロジカルな歯髄創傷治癒誘導-SIBLINGファミリー.

    鈴木茂樹( Role: Sole author ,  124:100-103)

    歯界展望  2014 

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  • 歯内療法学専門用語集 Glossary of Endodontics

    鈴木茂樹, 西村英紀( Role: Contributor ,  429神経ペプチドから447垂直破折まで: 43-44)

    医歯薬出版株式会社  2013 

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MISC

  • セメント芽細胞由来エクソソームによる破骨細胞分化制御 RANKL誘導性破骨細胞形成に対する増強作用

    佐藤 令, 丸山 顕太郎, 根本 英二, 向阪 幸彦, 鈴木 茂樹, 黎 家君, 沼崎 研人, 多田 浩之, 山田 聡

    日本歯周病学会会誌   64 ( 秋季特別 )   129 - 129   2022.8

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  • 新規PPARγアゴニストprocyanidin B2による歯周炎発症抑制とPPARγ遺伝子座転写産物の関与

    山本 真豊, 鈴木 茂樹, 佐藤 瞭子, 佐々木 健人, 大道寺 美乃, 根本 英二, 斎藤 正寛, 山田 聡

    日本歯周病学会会誌   64 ( 秋季特別 )   113 - 113   2022.8

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  • メカノレスポンス受容機構活性化による歯周組織再生

    佐藤 瞭子, 鈴木 茂樹, 山本 真豊, 佐々木 健人, 大道寺 美乃, 根本 英二, 齋藤 正寛, 山田 聡

    日本歯周病学会会誌   64 ( 秋季特別 )   110 - 110   2022.8

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  • 歯周病治療へのエピゲノム診断の利用を目指して

    鈴木 茂樹

    文部科学省共同利用・共同研究拠点 / 令和3年度生体医歯工学共同研究拠点成果報告会 / 第12回IDEA連携シンポジウム 抄録   2022.3

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  • 全身性強皮症患者に出現した多発性歯根外部吸収のメカニズム解明

    目見田 匠, 松田 真司, 鈴木 茂樹, 加治屋 幹人, 應原 一久, 岡信 愛, 畑野 紗希, 古玉 大祐, 柴 秀樹, 山田 聡, 水野 智仁

    日本歯周病学会会誌   63 ( 秋季特別 )   122 - 122   2021.10

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  • Development of regenerative medical therapy for hard tissues applying of hybrid recombinant Phosphophoryn.

    中西惇, 鈴木茂樹, 吉田和真, 平田(土屋)志津, 山田聡, 柴秀樹

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)   155th   2021.10

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    J-GLOBAL

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  • 周期的伸展刺激を受容したヒト歯根膜線維芽細胞はPGE2を介してM2マクロファージ分化を誘導する

    丸山 顕太郎, 佐藤 令, 向阪 幸彦, 鈴木 茂樹, 根本 英二, 山田 聡

    日本歯周病学会会誌   63 ( 秋季特別 )   139 - 139   2021.10

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  • PPARγ-induced global acetylation is required to maintain osteo/cementogenic abilities of periodontal ligament fibroblasts

    Yuan Hang, Shigeki Suzuki, Akiko Sato, Eiji Nemoto, Masahiro Saito, Hideki Shiba, Satoru Yamada

    日本歯周病学会会誌   63 ( 秋季特別 )   124 - 124   2021.10

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  • IκBζによるH3K4 のトリメチル化を介した反応性象牙質形成制御機構の解析

    鈴木茂樹, YUAN Hang, 平田(土屋)志津, 根本英二, 齋藤正寛, 柴秀樹, 山田聡

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)   155th   2021.10

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  • Elucidation mechanisms of multiple root resorption in systemic sclerosis patients

    Takumi Memida, Shinji Matsuda, Shigeki Suzuki, Mikihito Kajiya, Kazuhisa Ouhara, Ai Okanobu, Saki Hatano, Daisuke Furutama, Hideki Shiba, Satoru Yamada, Noriyoshi Mizuno

    63 ( 秋季特別 )   122 - 122   2021.10

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  • Human periodontal ligament fibroblasts that receive cyclic stretch induce M2 macrophage differentiation via PGE2.

    Kentaro Maruyama, Rei Sato, Yukihiko Sakisaka, Shigeki Suzuki, Eiji Nemoto, Satoru Yamada

    63 ( 秋季特別 )   139 - 139   2021.10

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  • The loss of IkBz accelerates dentin formation and matrix gene expression

    H. Yuan, S. Suzuki, H. Terui, S. Hirata-Tsuchiya, E. Nemoto, K. Yamasaki, M. Saito, H. Shiba, S. Aiba, S. Yamada

    The 69th Annual Meetings of Japanese Association for Dental Research   2021.10

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  • PPARγ is required for periodontal ligament cells to retain cemento/osteogeneity

    H. YUAN, S. SUZUKI, A. SATO, T. YAMAMOTO, E. NEMOTO, M. SAITO, S. YAMADA

    2020.11

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  • Effects of bone formation by drug repositioning of aspirin.

    HIRATA-TSUCHIYA Shizu, SUZUKI Shigeki, NAKANISHI Jun, TAKEDA Katsuhiro, SHIBA Hideki

    2020.11

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  • 間葉系幹細胞が高発現するMXRA5が持つ細胞増殖能・遊走能への効果

    吉田 和真, 鈴木 茂樹, 中西 惇, 平田 志津, 屋, 山田 聡, 柴 秀樹

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集 152回 114-114   2020.6

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  • PPARG is required for periodontal ligament cells to retain differentiation capacity of hard-tissue formation

    Yuan Hang,Shigeki Suzuki,Akiko Sato,Tadahiro Yamamoto,Eiji Nemoto,Masahiro Saito,Satoru Yamada

    日本歯周病学会会誌   62 ( 春季特別 )   125 - 125   2020.5

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  • メカノレスポンス因子MAP4K4の歯根膜における発現とその機能解析

    佐藤 瞭子, 鈴木 茂樹, 袁 航, 山本 真豊, 根本 英二, 齋藤 正寛, 山田 聡

    日本歯周病学会会誌 62(春季特別) 129-129   2020.5

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  • 炎症・メカニカル環境下における歯根膜細胞の新たな抗炎症システム~マクロファージIL-10分泌誘導因子の発現~

    佐藤令, 丸山顕太郎, 向阪幸彦, 根本英二, 鈴木茂樹, 山田聡

    日本歯周病学会会誌(Web)   62   2020

  • 精密マイクロパンチ加工で製作された純チタン多孔膜上における骨芽細胞様細胞培養

    ZHANG Jingyu, 向坂幸彦, 丸山顕太郎, 石幡浩志, 鈴木茂樹, 根本英二, 山田聡

    日本歯周病学会会誌(Web)   62   2020

  • NF-κB阻害薬MTI-IIはp65-Smad4複合体のSmad binding elementへの結合に関与する

    平田 志津, 鈴木 茂樹, 岡本 一起, 西藤 法子, 山田 聡, 柴 秀樹, 北村 知昭

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   151回   108 - 108   2019.10

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  • 周期的伸展刺激を受容したヒト歯根膜細胞はマクロファージからのIL-10産生を促進する

    丸山 顕太郎, 根本 英二, 鈴木 茂樹, 山田 聡

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   150回   98 - 98   2019.5

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  • DMP-1遺伝子座アンチセンス非翻訳長鎖RNAによる口腔上皮由来細胞の遊走能制御

    鈴木 茂樹, 袁 航, 栗田 真夏, 大森 雅人, 根本 英二, 山田 聡

    日本歯周病学会会誌   61 ( 春季特別 )   126 - 126   2019.5

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  • Heparinとの可逆的な結合は抗菌活性およびLPS中和能を減弱することなく、高濃度LL37の細胞障害性を改善する

    吉田 和真, 鈴木 茂樹, 中西 惇, 平田 志津[土屋], 山田 聡, 柴 秀樹

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   150回   92 - 92   2019.5

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  • Phosphophorynの抗炎症メカニズムの解析

    中西 惇, 鈴木 茂樹, 吉田 和真, 平田 志津[土屋], 山田 聡, 柴 秀樹

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   150回   91 - 91   2019.5

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  • DMP-1遺伝子座アンチセンス非翻訳長鎖RNAによる口腔上皮由来細胞の遊走能制御

    鈴木茂樹, YUAN Hang, 栗田真夏, 大森雅人, 根本英二, 山田聡

    日本歯周病学会会誌(Web)   61   2019

  • Long non-coding RNAs (lncRNAs)-mediated epigenetic status is possibly involved in the susceptibility of periodontal disease

    鈴木茂樹, Yuan Hang, 栗田真夏, 山田聡

    日本歯周病学会会誌(Web)   61 ( 1 )   2019

  • Effects of Aspirin on BMP-induced osteoblastogenesis.

    2018.11

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  • ヒト歯根膜細胞は周期的伸展刺激により抗炎症性エクソソームを分泌する

    王 祝愉, 根本 英二, 丸山 顕太郎, 鈴木 茂樹, 多田 浩之, 向阪 幸彦, 須藤 瑞樹, 山田 聡

    日本歯周病学会会誌   60 ( 秋季特別 )   118 - 118   2018.10

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  • ヒト歯根膜細胞は周期的伸展刺激により抗炎症性エクソソームを分泌する

    WANG Zhuyu, 根本英二, 丸山顕太郎, 鈴木茂樹, 多田浩之, 向阪幸彦, 須藤瑞樹, 山田聡

    日本歯周病学会会誌(Web)   60   2018

  • Phosphophorynの持つ抗炎症機能領域の探索.

    中西 惇, 鈴木茂樹, 吉田和真, 本山直世, 小武家誠司, 永安慎太郎, 平田, 土屋志津, 柴 秀樹

    特定非営利活動法人 日本歯科保存学会 2017年度秋季学術大会(第147回)プログラムおよび講演抄録集   2017.10

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  • クロマチン局在DMP‒1遺伝子による細胞増殖制御機構の解明.

    鈴木茂樹,吉田和真,中西 惇,平田‒土屋志津,小武家誠司,永安慎太郎,本山直世,柴 秀樹

    特定非営利活動法人 日本歯科保存学会 2017年度秋季学術大会(第147回)プログラムおよび講演抄録集   2017.10

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  • 抗菌ペプチドLL37 の宿主細胞傷害性低減を目指した複合体の開発

    吉田和真, 鈴木茂樹, 中西 惇, 小武家誠司, 本山直世, 永安慎太郎, 平田, 土屋志津, 柴 秀樹

    特定非営利活動法人 日本歯科保存学会 2017年度秋季学術大会(第147回)プログラムおよび講演抄録集   2017.10

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  • 培養ヒト歯髄細胞上清からの炎症促進Microvesicles の単離

    永安慎太郎,鈴木茂樹,中西 惇,吉田和真,小武家誠司,本山直世,土屋志津,西村英紀,柴 秀樹

    特定非営利活動法人 日本歯科保存学会 2017年度秋季学術大会(第147回)プログラムおよび講演抄録集   2017.10

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  • BMP‒Smad シグナルにMTI‒II Peptide Anti‒Inflammator y Drug(MPAID)が与える影響

    平田‒土屋志津,岡本一起,鈴木茂樹,本山直世,永安慎太郎,小武家誠司,柴 秀樹,北村知昭

    特定非営利活動法人 日本歯科保存学会 2017年度春季学術大会(第146回) プログラムおよび講演抄録集   2017.6

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  • マクロファージからのTNF‒α産生を誘導する歯髄細胞特異的因子の探索

    永安慎太郎,鈴木茂樹,中西 惇,吉田和真,土屋志津,本山直世,小武家誠司,柴 秀樹

    特定非営利活動法人 日本歯科保存学会 2016年度秋季学術大会(第145回) プログラムおよび講演抄録集   2016.10

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  • Heparin‒LL37複合体による抗菌作用の検討.

    吉田和真,鈴木茂樹,中西 惇,永安慎太郎,小武家誠司,柴 秀樹

    特定非営利活動法人 日本歯科保存学会 2016年度秋季学術大会(第145回) プログラムおよび講演抄録集   2016.10

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  • Phosphophoryn の持つ抗炎症作用の検討

    中西 惇,鈴木茂樹,小武家誠司,吉田和真,永安慎太郎,柴 秀樹

    特定非営利活動法人 日本歯科保存学会 2016年度春季学術大会(第144回) プログラムおよび講演抄録集   2016.6

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  • Phosphophorynのセリン・アスパラギン酸繰り返し配列の長さと細胞外基質石灰化効果との関連性

    小武家誠司, 鈴木茂樹, 星野博昭, 柴秀樹

    特定非営利活動法人 日本歯科保存学会 2015年度春季学術大会(第142回) プログラムおよび講演抄録集   2015.6

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  • The Effects of Matrix Trioxide Aggregate (MTA) on the Adhesion, Migration and Apoptosis of Dental Pulp Cells

    Shigeki SUZUKI, Shintaro NAGAYASU, Makoto ARAKAWA, Seiji KOBUKE, Hiroaki HOSHINO, Atsushi HASHIKATA, Tomotoku MOTOYAMA, Fusanori NISHIMURA

    Jpn J Conserv Dent   57 ( 6 )   547 - 554   2014.10

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    Purpose: Matrix trioxide aggregate (MTA) has been used for direct pulp-capping as well as perforation repair due to its potent ability to induce hard tissue regeneration. Pulp exposure, usually caused by tooth fracture and carious tooth treatment, involves the physical damage of pulp extracellular matrix. Therefore, when cells invade the damaged space from surrounding tissue, the existence of an adhesive substrate to aid cell proliferation and differentiation of invading cells is the key factor influencing the prognosis of pulp-capping treatment. In this study, we examined the effects of MTA on the adhesion, proliferation and apoptosis of human dental pulp cells (hDPCs) by comparison with composite resin (CR) and glass ionomer cement (GIC).<br> Materials and methods: Ninety-six-well plates were coated with MTA, CR, GIC and fibronectin. Cells were suspended in serum-free medium and then seeded onto coated wells. After 1.5-hr incubation at 37°C, the wells were rinsed to remove non-adherent cells. The number of adherent cells was quantified using the Cell Titer Glo Luminescent Cell Viability Assay Kit. For proliferation assay, these cells were seeded onto MTA, CR and GIC and attached cells were quantified. After 1.5-hr incubation, serum-free medium was replaced with 10% serum medium and cells were cultured onto these substrates for 72 hrs. The ability to induce apoptosis was evaluated by caspase 3/7 activity.<br> Result: MTA facilitated the adhesion of hDPCs, while CR and GIC did not. However, the adhesive effect of MTA was much weaker than that of fibronectin. hDPCs could attach onto MTA but not CR or GIC, even 72 hrs after seeding, although the number of attached cells gradually decreased during the culture period. These observations suggest that MTA could be used as a substrate for the adhesion, but not a scaffold for the proliferation, of hDPCs. A drastic increase of caspase 3/7 activity was observed when hDPCs were cultured onto CR and GIC. In contrast, MTA did not induce it.<br> Conclusions: Compared with CR and GIC, MTA is a good substrate for hDPC adhesion. These differential adhesive effects may be explained by the differential abilities for inducing pro-apoptotic signals in hDPCs. However, the effect of MTA as a cell adhesion substrate was much weaker than that of fibronectin. More importantly, MTA was unable to induce the proliferation of hDPCs on it. Thus, the co-addition of MTA with other adhesive and migratory proteins such as fibronectin may induce better wound healing and pulp tissue regeneration in vivo.

    DOI: 10.11471/shikahozon.57.547

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    Other Link: http://search.jamas.or.jp/link/ui/2015182150

  • 新規long non-coding RNAによるepigeneticなDMP-1遺伝子発現制御機構の解析

    星野博昭, 鈴木茂樹, 小武家誠司, 西村英紀

    特定非営利活動法人 日本歯科保存学会 2014年度春季学術大会(第140回)プログラムおよび抄録集   2014.6

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  • DPP4阻害薬anagliptinは、活性化マクロファージおよびマクロファージ共培養下脂肪細胞の炎症反応を抑制する

    山下 明子, 新城尊徳, 岩下未咲, 鈴木茂樹, 西村 英紀

    日本歯周病学会会誌 第56巻 春季特別号 平成26年5月   57 ( Supplement 1 )   2014.5

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  • DPP4阻害薬anagliptinは、活性化マクロファージおよびマクロファージ共培養下脂肪細胞の炎症反応を抑制する

    山下 明子, 新城 尊徳, 岩下 未咲, 鈴木 茂樹, 西村 英紀

    日本歯周病学会会誌   56 ( 春季特別 )   117 - 117   2014.4

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  • ヒトDMP-1遺伝子領域におけるlong non-coding RNAの同定

    星野博昭, 鈴木茂樹, 小武家誠司, 藤井理史, 西村英紀

    特定非営利活動法人 日本歯科保存学会 2013年度春季学術大会(第138回) プログラムおよび講演抄録集   2013.6

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  • LPS刺激マクロファージと共存したマウスメサンギウム細胞における発現遺伝子の網羅的解析

    箸方厚之, 山下明子, 鈴木茂樹, 永安慎太郎, 安孫子宜光, 西村英紀

    日本歯周病学会会誌 第55巻 春季特別号   2013.5

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  • 多毛症を合併した先天性歯肉増殖症患者由来歯肉線維芽細胞のカテプシン活性の検討

    荒川真,半井英雄,山下明子,岩本義博,鈴木茂樹,西村英紀

    日本歯周病学会会誌 第55巻 春季特別号   2013.5

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  • 低濃度LPS刺激条件下のメサンギウム細胞・マクロファージ共培養系におけるメサンギウム細胞の網羅的遺伝子発現解析

    山下 明子, 箸方 厚之, 岩下 未咲, 鈴木 茂樹, 安孫子 宜光, 櫛山 暁史, 浅野 知一郎, 西村 英紀

    糖尿病   2013.4

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  • Dentin sialophosphoproteinの開裂がその機能発現に及ぼす影響の検討

    小武家誠司、鈴木茂樹、藤井理史、西村英紀

    特定非営利活動法人 日本歯科保存学会 2012年度秋季学術大会(第137回)プログラムおよび講演抄録集   2012.11

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  • 歯髄細胞が産生するTNF-alpha誘導因子の探索

    永安慎太郎, 鈴木茂樹, 小武家誠司, 山下明子, 安孫子宣光, 西村英紀

    特定非営利活動法人 日本歯科保存学会 2012年度秋季学術大会(第137回)プログラムおよび講演抄録集   2012.11

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  • 歯周炎症と糖尿病性腎症の関連性解明に向けた基礎研究

    山下明子,箸方厚之,鈴木茂樹,岩下未咲,西村英紀

    日本歯周病学会会誌 54(秋季特別)   2012.9

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  • Dentin Sialophosphoprotein Cleavage is Critical for Its Functional Expression.

    Suzuki S, Nishimura F

    2012.6

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  • ココアフラボノールの心血管イベント 抑制効果機序の検討~脂肪細胞・ マクロファージ相互作用の観点から~

    永安慎太郎, 山下明子, 鈴木茂樹, 安孫子宜光, 西村英紀

    日本歯周病学会会誌 54(春季特別)   2012.5

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  • TLR-4リガンド刺激マクロファージと共存する脂肪細胞で発現するケモカインの網羅的解析

    雁瀬朋美,永安慎太郎,山下明子,鈴木茂樹,安孫子宜光,西村英紀

    日本歯周病学会会誌 54(春季特別)   2012.5

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  • 局所の慢性炎症が惹起するインスリン抵抗性などのメタボリックシンドロームに関わるmiRNAの網羅的解析

    山下明子, 鈴木茂樹, 安孫子宜光, 西村英紀

    第55回日本糖尿病学会年次学術集会   2012.5

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  • ダークココアの動脈硬化抑制作用の検討 エピカテキンの抗炎症作用の観点から

    永安 慎太郎, 山下 明子, 鈴木 茂樹, 岩下 未咲, 安孫子 宜光, 西村 英紀

    日本歯周病学会会誌   54 ( 春季特別 )   115 - 115   2012.4

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  • マクロファージと共存する脂肪細胞をLPS刺激した際に発現変動するmiRNAの網羅的解析

    山下 明子, 岩下 未咲, 鈴木 茂樹, 櫛山 暁史, 安孫子 宜光, 浅野 知一郎, 西村 英紀

    糖尿病   2012.4

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  • 歯髄細胞が産生する因子のゲノミクス,プロテオミクス解析

    小武家誠司,鈴木茂樹,米廣純子,半井英雄,藤井紗貴子,西村英紀

    特定非営利活動法人 日本歯科保存学会 2011年度秋季学術大会(第135回) プログラムおよび講演抄録集   2011.10

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  • Dentin sialophosphoprotein の骨芽細胞分化誘導作用ならびにそのメカニズムの解析.

    鈴木茂樹,小武家誠司,西村英紀

    特定非営利活動法人 日本歯科保存学会 2011年度秋季学術大会(第135回) プログラムおよび講演抄録集   2011.10

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  • 喫煙がレプチン産生に与える影響についての検討

    永安慎太郎,山下明子,鈴木茂樹,岩下未咲,西村英紀

    特定非営利活動法人 第54回日本歯周病学会秋季学術大会 プログラムおよび講演抄録集   53 ( 秋季特別 )   114 - 114   2011.9

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  • ココアフラボノイドの心血管イベント抑制効果機序の解析―脂肪細胞マクロファージ相互作用の観点から.

    山下明子,永安慎太郎,鈴木茂樹,岩下未咲,半井英雄,安孫子宜光,西村英紀

    第54回日本糖尿病学会年次学術集会   2011.5

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  • 2 型糖尿病患者におけるココアフラボノールの心血管イベント抑制効果機序の検討~脂肪細胞・マクロファージ相互作用の観点から~

    永安慎太郎,山下明子,鈴木茂樹,安孫子宜光,西村英紀

    特定非営利活動法人 第54回日本歯周病学会春季学術大会 プログラムおよび講演抄録集   2011.5

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  • ココアフラボノールの抗炎症作用による動脈硬化抑制作用の検討

    永安 慎太郎, 山下 明子, 鈴木 茂樹, 半井 英雄, 岩下 未咲, 熊本 園子, 安孫子 宜光, 西村 英紀

    日本歯周病学会会誌   53 ( 春季特別 )   107 - 107   2011.4

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  • The establishment of stable cell lines expressing cleavage-resistant Dentin sialophosphoprotein.

    Suzuki S, Nishimura F

    The 89th General Session & Exhibition of the International Association for the Dental Research   2011.3

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  • Study on inhibitory effects of Cacao flavonol on arteriosclerosis by its anti-inflammatory action.

    Nagayasu Shintaro, Yamasita Akiko, Suzuki Sigeki, Nakarai Hideo, Iwasita Misaki, Kumamoto Sonoko, Abiko Yosimitu, Nisimura Fusanori

    Program and Abstracts of Annual Meeting of the Japanese Society of Periodontology   2011   23 - 23   2011

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    DOI: 10.14833/amjsp.2011s.0.23.0

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  • Adipose tissue inflammation and smoking synergistically suppress leptin expression in Japanese obese males. Potential mechanism of resistance to weight loss among obese smokers.

    Nagayasu S, Yamashita A, Suzuki S, Iwasita M, Nishimura F

    The 4th International Workshop on BioDental Education and Research   2011

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  • 開裂抵抗性Dentin sialophosphoprotein発現株の作製

    鈴木茂樹, 小武家誠司, 西村英紀

    特定非営利活動法人 日本歯科保存学会 2010年度秋季学術大会(第133回)プログラムおよび講演抄録集   2010.10

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  • ココアフラボノールの心血管イベント抑制効果の機序の検討-脂肪細胞・マクロファージ相互作用の観点から

    永安慎太郎,山下明子,鈴木茂樹,半井英雄,安孫子宜光,西村英紀

    第53回秋季日本歯周病学会学術大会 プログラムおよび講演抄録集   2010.9

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  • ココアフラボノールの心血管イベント抑制効果機序の検討-脂肪細胞・マクロファージ相互作用の観点から.

    永安慎太郎,山下明子,鈴木茂樹,半井英雄,安孫子宜光,西村英紀

    第25回日本糖尿病合併症学会   2010

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  • 象牙質形成におけるDentin sialoprotein及びDentin phosphoproteinの機能解析

    鈴木茂樹, 西村英紀

    特定非営利活動法人 日本歯科保存学会 2009年度秋季学術大会(第131回) プログラムおよび講演抄録集   2009.10

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  • ウェルナー症候群における歯周病の実態

    荒川真,鈴木茂樹,山下明子,白井憲一,藤井理史,西村英紀

    特定非営利活動法人 日本歯科保存学会 2009年度秋季学術大会(第131回) プログラムおよび講演抄録集   2009.10

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  • Dentin sialoprotein and dentin phosphoprotein have distinct roles in dentin mineralization.

    Suzuki S, Nishimura F

    2009

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  • Molecular Roles of Dentin Sialophosphoprotein in Tooth Development and Mineralization.

    Suzuki S, Sreenath T, Haruyama N, Honeycutt C, Terse A, Kohler T, Müller R, Goldberg M, Kulkarni AB

    National Institutes of Health Research Festival   2008

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  • Molecular Roles of Dentin Sialophosphoprotein in Tooth Development and Mineralization.

    Suzuki S, Terse A, Cho A, Honeycutt C, Haruyama N, Sreenath T, Goldberg M, Kulkarni AB

    2008

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  • 歯根膜細胞硬組織形成分化過程におけるSFRP4とWnt5aの関与.鈴木茂樹* Reviewed

    鈴木茂樹

    大阪大学齒學雑誌   51   1 - 21   2007

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  • Characterization of the molecular roles of dentin sialoprotein (DSP) in dentin biomineralization.

    Suzuki S, Haruyama N, Cho A, Honeycutt C, Sreenath T, Kulkarni AB

    The 9th International Conference on the Chemistry and Biology of Mineralized Tissues (ICCBMT)   2007

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  • 歯周組織再生療法 歯根膜細胞分化におけるWnt/SFRPの関与

    山田 聡, 鈴木 茂樹, 村上 伸也

    Inflammation and Regeneration   26 ( 4 )   299 - 299   2006.7

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  • Participation of Wnt5a/SFRP4 in the differentiation process of periodontal ligament cells

    SUZUKI Shigeki, YAMADA Satoru, TOMOEDA Miki, YONEDA Shinya, FUJIWARA Chiharu, MURAKAMI Shinya

    日本歯周病学会会誌   48   136 - 136   2006.3

  • ヒト歯根膜細胞の硬組織形成分化過程における全遺伝子発現プロファイリング解析

    米田 晋也, 山田 聡, 鈴木 茂樹, 友枝 美樹, 田内 拓史, 野崎 剛徳, 北村 正博, 村上 伸也

    日本歯周病学会会誌   47 ( 秋季特別 )   116 - 116   2005.8

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  • 歯根膜細胞分化過程におけるSFRP4の関与

    鈴木 茂樹, 山田 聡, 前田 憲一郎, 友枝 美樹, 米田 晋也, 北垣 次郎太, 松原 謙一, 村上 伸也

    炎症・再生   25 ( 4 )   367 - 367   2005.7

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  • PerioGen Chipにより同定されたDAN遺伝子のヒト歯根膜細胞分化への関与

    前田 憲一郎, 山田 聡, 鈴木 茂樹, 友枝 美樹, 米田 晋也, 野崎 剛徳, 北村 正博, 村上 伸也

    日本歯周病学会会誌   47 ( 春季特別 )   53 - 53   2005.3

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  • Functional Analysis of PLAP-1 through RNA interference (RNAi).

    Tomoeda M, Yamada S, Maeda K, Suzuki S, Kitamura M, Murakami S

    The 83th General Session & Exhibition of the International Association for the Dental Research   2005

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  • Participation of Wnt5a/SFRP4 in the differentiation process of periodontal ligament cells.

    Suzuki S, Yamada S, Maeda K, Murakami S

    The 83th General Session & Exhibition of the International Association for the Dental Research   2005

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  • Participation of Wnt/SFRP in the differentiation process of periodontal ligament cells

    SUZUKI Shigeki, YAMADA Satoru, KITAGAKI Jirota, MAEDA Kenichiro, TOMOEDA Miki, YONEDA Shinya, MURAKAMI Shinya

    日本歯周病学会会誌   46 ( 秋季特別 )   91 - 91   2004.9

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  • Specific Expression and Functions of PLAP-1 in Periodontal Ligament

    TOMOEDA Miki, YAMADA Satoru, OZAWA Yasuhiro, MAEDA Kenichiro, SUZUI Shigeki, MURAKAMI Shinya

    日本歯周病学会会誌   46 ( 春季特別 )   146 - 146   2004.4

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  • Expression analysis of FGF-2-responsive genes utilizing the customized DNA chip (PerioGen Chip)

    SUZUKI Shigeki, YAMADA Satoru, OZAWA Yasuhiro, MAEDA Kenichiro, TOMOEDA Miki, NOZAKI Takenori, KITAMURA Masahiro, MURAKAMI Shinya

    日本歯周病学会会誌   45 ( 秋季特別 )   85 - 85   2003.9

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  • Construction and application of cDNA microarray specialized for periodontal ligament.

    JOURNAL OF DENTAL RESEARCH   225 - 225   2003.6

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  • Functional Analysis of PLAP-1 in Mineralized Matrix Formation

    OZAWA Yasuhiro, YAMADA Satoru, NAKAHIRA Yo, MAEDA Kenichiro, SUZUKI Sigeki, YOKOKOJI Takayoshi, IKEZAWA Kazuhiko, MURAKAMI Shinya

    日本歯周病学会会誌   45 ( 春季特別 )   115 - 115   2003.4

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  • カスタマイズドDNAチップ(PerioGen Chip)を用いた歯根膜細胞遺伝子発現の解析

    前田 憲一郎, 山田 聡, 中平 陽, 小澤 康宏, 鈴木 茂樹, 野崎 剛徳, 北村 正博, 村上 伸也

    日本歯周病学会会誌   45 ( 春季特別 )   119 - 119   2003.4

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  • Functional analysis of PLAP-1 in mineralized matrix formation.

    Y. Ozawa, S. Yamada, Y. Nakahira, K. Maeda, S. Suzuki, T. Yokokoji, S. -I. Takayama, K. Ikezawa, S. Murakami

    JOURNAL OF DENTAL RESEARCH   380 ( 380 )   2003.4

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  • 歯根膜組織由来カスタマイズドDNAチップ(PerioGen Chip)の作製とその応用

    山田 聡, 前田 憲一郎, 鈴木 茂樹, 中平 陽, 小澤 康宏, 野崎 剛徳, 北村 正博, 村上 伸也

    大阪大学歯学雑誌   47 ( 2 )   132 - 132   2003.4

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Presentations

  • 招待講演:Tissue Engineering session `Epigenetic reprogramming of odontoblasts for regenerative medicine: loss of IκBζ drives dentin formation via altered H3K4me3 status` Invited

    Shigeki Suzuki

    The International Oral Health Symposium 2022: Innovation, Strategy, and Future Perspectives hoted by Karolinska Institute  2022.6.7 

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    Event date: 2022.6.7 - 2022.6.8

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  • Metabolites Epigenetically Regulate Periodontal Tissue Homeostasis

    Shigeki Suzuki

    022 IADR/APR General Session & Exhibition Focused Learning Session  2022.6.23 

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  • 歯根膜細胞はエネルギー代謝機構を利用して分化能を維持している Invited

    鈴木茂樹

    第64回春季日本歯周病学会学術大会 第54回若手研究者の集い  2021.5.20 

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  • PPAR gamma-induced global H3K27 acetylation is required to maintain the abilities of extracellular matrix organization and osteo/cementogenesis in periodontal ligament fibroblasts: the possible link between dietary unsaturated fatty acids and periodontal tissue homeostasis Invited

    Shigeki Suzuki

    The 69th Annual Meeting of Japanese Association for Dental Research (JADR)  2021 

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  • 招待講演:第152回日本歯科保存学会シンポジウム3:歯周組織の恒常性維持機構を再考する Invited

    鈴木茂樹

    第152回日本歯科保存学会  2020 

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  • Isolation of pro-inflammatory extracellular vesicles from human dental pulp cells Invited International conference

    Shigeki Suzuki

    7th Hiroshima Conference on Education and Science in Dentistry  2018.3 

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  • The usefulness of the modified recombinant phosphophoryn in the hard tissue regeneration

    Shigeki Suzuki

    The 6th International Workshop on BioDental Education and Research, Hiroshima Peace Seminar  2015.10 

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  • 招待講演:サテライトシンポジウム12「Dentin Sialophosphoprotein (DSPP) を形態と機能から考える」講演タイトル:改変型組み換えDPPタンパク質を利用した硬組織再生における有用性. Invited

    鈴木茂樹

    第57回歯科基礎医学会学術大会  2015 

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  • 招待講演:「若手研究者が描くPulp Wound Healing & Regeneration」 講演タイトル:内在性Wntによる歯髄創傷治癒促進効果とDentin Phosphoproteinによる硬組織形成作用の検討. Invited

    鈴木茂樹

    第138回日本歯科保存学会春季学術大会シンポジウムI,  2013 

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  • The functional analysis of dentin sialophosphoprotein during dentin development. Invited International conference

    Shigeki Suzuki

    2010 

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Awards

  • 2023年度年間優秀論文 賞(歯内療法学分野)

    2024.5   日本歯科保存学会  

    鈴木 茂樹, 長谷川 龍, 佐藤 瞭子, 大道寺 美乃, 長﨑 果林, 根本 英二, 山田 聡

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  • 第155回松風優秀ポスター賞

    2021.10   日本歯科保存学会  

    鈴木 茂樹, 袁 航, 平田-土屋 志津, 根本 英二, 齋藤 正寛, 柴 秀樹, 山田 聡

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  • デンツプライ賞

    2010.6   日本歯科保存学会  

    鈴木茂樹

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  • 奨励賞

    2010.6   日本歯科保存学会  

    鈴木茂樹

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  • National Institutes of Health Visiting Program Award, USA,

    2007.8   National Institutes of Health, USA,  

    鈴木茂樹

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Research Projects

  • 歯周組織再生におけるRANK発現EVsの機能解析とその治療応用への基盤構築

    Grant number:24K12906  2024.04 - 2027.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    向阪 幸彦, 鈴木 茂樹, 根本 英二, 山田 聡

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    Grant amount:\4550000 ( Direct expense: \3500000 、 Indirect expense:\1050000 )

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  • シングルセルゲノミクスとPheWAS解析による歯周病の個別化医療・予防の確立

    Grant number:23K27767  2024.04 - 2026.03

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    山田 聡, 鈴木 茂樹, 大槻 晃史, 村上 伸也, 梶川 哲宏

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    Grant amount:\12740000 ( Direct expense: \9800000 、 Indirect expense:\2940000 )

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  • エフェロサイトーシスを基軸とした歯周組織恒常性維持機構の解明と治療への応用

    Grant number:23K24523  2024.04 - 2025.03

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    梶川 哲宏, 鈴木 茂樹, 山田 聡

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    Grant amount:\3120000 ( Direct expense: \2400000 、 Indirect expense:\720000 )

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  • 再生指向型エピゲノムに基づく歯周組織再生術前診断法と精密化療法の樹立

    Grant number:23K24524  2024.04 - 2025.03

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    鈴木 茂樹, 根本 英二, 山田 聡, 梶川 哲宏

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    Grant amount:\4550000 ( Direct expense: \3500000 、 Indirect expense:\1050000 )

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  • 歯周組織特異的CAR-MSC細胞を用いた革新的な歯周組織再生移植治療への挑戦

    Grant number:23K18350  2023.06 - 2025.03

    日本学術振興会  科学研究費助成事業  挑戦的研究(萌芽)

    山田 聡, 向阪 幸彦, 齋藤 正寛, 梶川 哲宏, 鈴木 茂樹

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    Grant amount:\6240000 ( Direct expense: \4800000 、 Indirect expense:\1440000 )

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  • シングルセルゲノミクスとPheWAS解析による歯周病の個別化医療・予防の確立

    Grant number:23H03077  2023.04 - 2026.03

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    山田 聡, 鈴木 茂樹, 大槻 晃史, 村上 伸也, 梶川 哲宏

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    Grant amount:\18330000 ( Direct expense: \14100000 、 Indirect expense:\4230000 )

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  • 高分化型セメント細胞エクソソームを軸としたセメント質形成と歯周組織再生への応用

    Grant number:23K09163  2023.04 - 2026.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    根本 英二, 鈴木 茂樹, 山田 聡

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    Grant amount:\4810000 ( Direct expense: \3700000 、 Indirect expense:\1110000 )

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  • in situ象牙芽細胞ダイレクトリプログラミングへの挑戦

    Grant number:22K19611  2022.06 - 2024.03

    日本学術振興会  科学研究費助成事業  挑戦的研究(萌芽)

    鈴木 茂樹, 山崎 研志, 山田 聡, 土屋 志津

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    Grant amount:\6240000 ( Direct expense: \4800000 、 Indirect expense:\1440000 )

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  • 再生指向型エピゲノムに基づく歯周組織再生術前診断法と精密化療法の樹立

    Grant number:22H03266  2022.04 - 2025.03

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    鈴木 茂樹, 根本 英二, 山田 聡, 梶川 哲宏

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

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  • エフェロサイトーシスを基軸とした歯周組織恒常性維持機構の解明と治療への応用

    Grant number:22H03265  2022.04 - 2025.03

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    梶川 哲宏, 鈴木 茂樹, 山田 聡

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    Grant amount:\17810000 ( Direct expense: \13700000 、 Indirect expense:\4110000 )

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  • 歯を用いた幼少期逆境体験の遡及的定量法の開発

    2022

    科学技術振興機構  研究成果展開事業 大学発新産業創出プログラム 大学・エコシステム推進型 スタートアップ・エコシステム形成支援 

    鈴木 茂樹, 天雲 太一, 山田 聡, 斎藤 幹

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\9100000 ( Direct expense: \7000000 、 Indirect expense:\2100000 )

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  • RANKL逆シグナルと破骨細胞エクソソームを基軸とした新規歯周組織再生療法の開発

    Grant number:21K09868  2021.04 - 2024.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    向阪 幸彦, 鈴木 茂樹, 根本 英二, 山田 聡, 丸山 顕太郎

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

    エクソソームは、細胞から分泌される膜小胞であり、タンパク質のみならずメッセンジャーRNAやマイクロRNAなども含めた膨大な情報伝達物質を他の細胞に伝達する役割がある。近年、破骨細胞が分泌するエクソソーム上に発現しているRANKが、骨芽細胞のRANKLと結合することで骨芽細胞の分化を誘導することが報告されている。一方でセメント質の研究に関しては、セメント芽細胞が発現しているRANKLが破骨細胞のRANKを介して破骨細胞分化を誘導することが報告されているが、破骨細胞由来のエクソソームがセメント芽細胞分化に与える影響については報告が皆無である。本研究の目的は、破骨細胞由来のRANK発現エクソソームによるセメント芽細胞の分化誘導を検証することである。
    今年度は破骨細胞分泌エクソソームがセメント芽細胞に与える作用について検証した。まずマウスマクロファージ様細胞株RAW264.7をリコンビナントRANKL存在下にて5日間培養し破骨細胞分化を誘導した。その過程で培養3~5日目の上清を回収し、ExoQuick-TCエクソソーム単離キットを用いてエクソソームを単離した。セメント芽細胞の前駆細胞と考えられているマウス歯小嚢細胞株SVF4に単離したエクソソームで1日刺激した後にリコンビナントWnt3aで分化誘導を行ったところ、エクソソームの濃度依存的にSVF4のアルカリフォスファターゼ活性を抑制することを認めた。
    次年度は上記の知見におけるシグナル解析を行うとともに、SVF4のRANKLの発現誘導あるいは抑制を行った条件下での破骨細胞由来エクソソームの作用を検討する。

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  • Retrospective quantitative analysis of juvenile stress using dentin matrix

    Grant number:20K21668  2020.07 - 2022.03

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

    YAMADA SATORU

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    Grant amount:\6370000 ( Direct expense: \4900000 、 Indirect expense:\1470000 )

    Mice were intravenously administrated corticosterone at early childhood or juvenile stage and the amount of corticosterone in mineralized hard tissue of their teeth was quantified by ELISA method. The results revealed that corticosterone was detected in mineralized hard tissue of the teeth of corticosterone-injected group but not PBS-injected control group. This result suggested that systemically administrated corticosterone could be deposited into hard tissue of teeth. Corticosterone level in circulation of the mice received early life stress was significantly higher than that of control mice (p=0.0019). Corticosterone level in hard tissue of the teeth of adult mice that have experienced early life stress was 0.5343 pg/mg and that of control adult mice was 0.3547 mg/kg (p = 0.2046). These results indicated that corticosterone induced by early life stress at early childhood stage possibly accumulated in hard tissue of the teeth and corticosterone level was retained during the lifespan.

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  • WNT・メカノシグナルによる歯根膜幹細胞エクソソームの最適化と歯周組織再生制御

    Grant number:20K09933  2020.04 - 2023.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    根本 英二, 鈴木 茂樹, 山田 聡

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

    当該年度は,歯根膜組織に局在する細胞としてマウス由来セメント芽細胞に焦点を当てて研究を行なった。マウス由来セメント芽細胞由来エクソソームの破骨細胞分化誘導系に及ぼす影響について解析した。
    マウスセメント芽細胞株OCCM-30の培養上清からエクソソームを抽出した。透過電子顕微鏡解析を行ったところ,直径約50~200 nmのエクソソームが存在することが確認された。マウス破骨細胞前駆細胞株RAW264.7細胞を,リコンビナントreceptor activator of nuclear factor-κB ligand(rRANKL)刺激により破骨細胞へ分化させる実験系を用いて,エクソソームの影響を調べた。エクソソームは,rRANKLによって誘導される酒石酸耐性酸性ホスファターゼ(TRAP)活性陽性細胞の形成を増強した。また,リアルタイムPCR法およびWestern blot法による解析から,エクソソームは,rRANKL刺激による破骨細胞関連遺伝子およびタンパクの発現誘導に対しても増強することが明らかとなった。一方,rRANKL非存在下では,細胞外小胞による破骨細胞分化増強作用は認められなかった。Western blot法の解析から,エクソソーム自体にはRANKLの発現は検出されなかった。一方,セメント芽細胞の細胞培養上清を用いて,rRANKL誘導性破骨細胞分化に与える影響について,TRAP活性陽性細胞の形成および破骨細胞関連遺伝子の発現の観点から調べた。細胞培養上清は,rRANKL誘導性破骨細胞分化を部分的に抑制するとともに,エクソソームによるその増強作用に対して,ほぼ完全に抑制することが明らかとなった。
    以上のことから,セメント芽細胞から分泌されるエクソソームは,rRANKL誘導性破骨細胞分化に対して増強作用を有していることが明らかとなった。

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  • 共役因子MTI-Ⅱによるエストロゲンシグナル調節を介した硬組織再生療法の開発

    Grant number:20K09956  2020.04 - 2023.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    土屋 志津, 柴 秀樹, 自見 英治郎, 鈴木 茂樹

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

    女性ホルモンであるエストロゲンは様々な疾患の発症・進展の抑制に寄与する。エストロゲンは骨のリモデリングにも関与し、更年期以降のエストロゲン欠乏が骨粗鬆症の原因となることが知られている。これまでに申請者らは、「炎症制御による硬組織再生誘導」という視点から、骨芽細胞や象牙芽細胞様細胞において、グルココルチコイド受容体の共役因子Macromolecular Translocation Inhibitor-II(MTI-II)が高い抗炎症および硬組織誘導能を持つことを報告した。エストロゲン受容体とグルココルチコイド受容体は高い相同性を有するため本研究では、MTI-IIの持つ抗炎症能・硬組織形成能と、エストロゲン作用増強能を利用した硬組織再生法を開発することを目的としている。
    今年度はまず、ヒト歯髄細胞へのエストロゲンの影響を調べた。広島大学 疫学研究倫理審査委員会で承認後、研究への同意が得られた患者の抜去歯から歯髄細胞を樹立し、エストロゲンレセプター(ERa, ERb)の発現が見られるかをRT-PCR法で調べたところ、どちらの発現も確認できた。次にエストロゲン(17β-Estradiol: E2)を刺激してERaとERbの発現を確認したが、どちらもE2刺激による発現上昇は見られなかった。次に樹立した歯髄細胞の性差による硬組織形成能を比較するため、骨形成因子Bone Morphogenetic Protein-4 (BMP4) 刺激によるALP活性と遺伝子の発現変化を調べたところ、ALP活性に有意な差は認められなかった。どちらの細胞からも、BMP Response geneであるId1の遺伝子発現の上昇が認められた。

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  • 疾患由来iPS細胞レジストリとPLAP-1を基軸とした侵襲性歯周炎の分子病態解明

    Grant number:20H03862  2020.04 - 2023.03

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    山田 聡, 森崎 隆幸, 江草 宏, 鈴木 茂樹, 根本 英二, 村上 伸也, 梶川 哲宏

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    Grant amount:\17550000 ( Direct expense: \13500000 、 Indirect expense:\4050000 )

    本研究では、未だその発症・進行メカニズムの詳細が不明な侵襲性歯周炎(AgP)において、患者由来iPS細胞レジストリ(AgP-iPS細胞レジストリ)を構築し、同細胞レジストリを用いて網羅的な全ゲノム解析と細胞分化機能解析を同時に行うことで、侵襲性歯周炎の原因となる複数の新たなる遺伝子変異群を決定することを目的としている。さらには、申請者らのこれまでの研究結果から、侵襲性歯周炎原因遺伝子の一つであることが示唆されるPLAP-1/Asporinについて、AgPレジストリにおけるPLAP-1遺伝子多型解析を行うことで、PLAP-1が、侵襲性歯周炎の原因遺伝子であることを証明することを目的としている。2021度は、侵襲性歯周炎患者由来iPS細胞レジストリ構築のため、侵襲性歯周炎患者の歯周基本治療および歯周外科処置時に通常は廃棄される不良肉芽組織を回収し、回収した組織からiPS細胞作製用の培養線維芽細胞を樹立するための学内倫理研究申請を行った。さらには、健常者由来iPS細胞を用いてiPS細胞の培養系ならびに間葉系間質細胞と骨芽細胞分化誘導系の確立を行っている。さらに、侵襲性歯周炎と診断された患者の末梢血からゲノムDNAを抽出し、同DNAを大阪大学侵襲性歯周炎ゲノムバンクへ送ることで、レジストリを構築した。また、PLAP-1遺伝子多型が見られるアスパラギン酸リピート数の差異がPLAP-1タンパクの機能におよぼす影響を解析することを目的として、リピート数の異なる哺乳類細胞由来組み換えPLAP-1タンパクを発現・作製するためのベクターシステムを構築した。

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  • 長鎖非翻訳RNAによる歯周炎発症制御機構の解明

    2019 - 2021

    日本学術振興会:科学研究費助成事業  基盤(C) 

    鈴木茂樹

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    Authorship:Principal investigator  Grant type:Competitive

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  • Studies on the Pathophysiological role of TRPV3 in skin wound healing and pressure ulcers

    Grant number:18K19715  2018.06 - 2021.03

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

    Sanai Mari

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    Grant amount:\6240000 ( Direct expense: \4800000 、 Indirect expense:\1440000 )

    In this study, we investigated the effect of TRPV3 on wound healing. Intradermal administration and application of TRPV3 activator to the periwound area in skin defect, skin ulcer, and pressure ulcer models resulted in the formation of high quality granulation rich in neovascularization and accelerated wound atrophy, and at the same time, a strong pruritic reactions (scratching and biting) was also evoked. In vitro scratch assay also showed a tendency to accelerate wound healing. Furthermore, we have obtained data suggesting that skin TRPV3 may not be sufficiently activated at the skin temperature (<32°C) of the living body. We are currently investigating the effective use of TRPV3 activator, but we have not yet been able to distinguish between wound healing and pruritus. If we can control wound healing and pruritus of TRPV3 separately, it will contribute to the development of new therapies, drugs and clinical applications for intractable ulcers and pressure ulcer.

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  • Homeodynamics analysis of periodontal ligament tissue

    Grant number:17H04417  2017.04 - 2020.03

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

    Yamada Satoru

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

    In this study, we performed comprehensive transcriptome analyses to identify novel genes and molecules which are involved in periodontal tissue homeostasis. We analyzed periodontal disease animal models using a gene modified mouse to investigate more details of molecular mechanisms of periodontal medicine in terms of homeodynamics.

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  • Development of endodontic treatment through the NF-kB inhibition by the NSAIDs repositioning

    Grant number:17K11706  2017.04 - 2020.03

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

    Tsuchiya Shizu

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

    In the present study, we investigated the effect of aspirin on osteoblast differentiation and its mechanism, and simultaneously demonstrated its potential as a newly repositioned drug in bone tissue formation and suppressing inflammation. Low-dose aspirin enhanced bone morphogenetic protein (BMP)-induced ALP activity. Low-dose aspirin enhanced BMP-induced expression of Osteocalcin, Osterix, and Runx2 mRNA, markers of osteoblasts. These results suggest that low-dose aspirin accelerates the differentiation of BMP-induced osteoblasts.

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  • DPP/DMP-1ハイブリッド組み換えタンパク質を利用した硬組織再生法の樹立

    Grant number:16K11552  2016.04 - 2017.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    峯岡 茜, 鈴木 茂樹, 柴 秀樹

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

    DSPP (Dentin sialophosphoprotein) と Dentin Matrix protein-1 (DMP-1) は歯髄・象牙質に多量に存在し、DSPPの開裂C側タンパク質DPP (Dentin phosphoprotein 別名PP: Phosphophoryn) は高度にリン酸化されたSer-Aspの繰り返し配列を持ち、この繰り返し配列は歯を持つすべての動物のDPPに見られることから、DPPは歯牙硬組織形成に必須であると考えられている。DMP-1の開裂C側タンパク質C-DMP-1とDPPはインテグリン結合配列RGD (Arg-Gly-Asp) を持つが、C-DMP-1のRGDのみが細胞刺激活性を有する。本研究ではDPPおよびC-DMP-1の各活性部位をハイブリッドさせた人工組み換えタンパク質(以下rDPP -DMP-1-RGDと表記する)を作製し、その硬組織形成能をin vivo実験モデルで評価し、将来的な臨床応用の可能性を探求することを目的としていた。本研究計画においては多量の組み換えタンパク質を得るためにDPP内のSer-Aspの繰り返し配列を63.5%欠失させたrDPP並びにrDPP -DMP-1-RGDを利用した。陰イオンクロマトグラフィーで精製したrDPPをコートした培養皿にはMG63細胞は接着しなかったが、同様に作製したrDPP -DMP-1-RGDをコートした培養皿では著明な細胞接着を認めた。このことからDPPはDMP-1型のRGDを持つことで細胞接着能を獲得することが明らかとなった。さらに、これらrDPPまたはrDPP -DMP-1-RGD含有ハイドロキシアパタイト担体にヒト間葉系幹細胞を浸漬させ、ヌードマウスに皮下移植した。

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  • 新規同定した長鎖非翻訳RNAによる歯髄細胞増殖・分化誘導機序の解明.

    2016 - 2018

    日本学術振興会  科学研究費助成事業 基盤(C) 

    鈴木茂樹

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    Authorship:Principal investigator  Grant type:Competitive

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  • Usefulness of the complex of the three regenerative elements as a therapeutic agent for regeneration against endodontic diseases

    Grant number:15H05022  2015.04 - 2018.03

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

    Shiba Hideki

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    Grant amount:\17420000 ( Direct expense: \13400000 、 Indirect expense:\4020000 )

    Cells, scaffolds and regulatory factors are the three key elements for tissue engineering. LL37 possesses broad-ranged bactericidal effects and angiogenesis ability, indicating LL37 is a candidate for a regulatory factor. However, LL37 is known to exhibit cytotoxic properties for host cells. Therefore, the development of LL37-complexes, by which the cytotoxicity for host cells is eliminated without antimicrobial abilities diminished, is essential for future clinical application. We demonstrated that LL37 (10 microM) premixed with heparin (2-8 microg/ml), one of glycosaminoglycans, did not show any cytotoxic effects but retained bactericidal effects. In addition, heparin-LL37 complex had cell-functioning ability. These findings suggest that the heparin-LL37 complex is a promising regulatory factor for regenerative therapy.

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  • インテグリン結合RGD配列の近傍切断によるシグナル増強と歯髄組織創傷治癒誘導.

    2014 - 2015

    日本学術振興会  科学研究費助成事業 若手研究(B) 

    鈴木茂樹

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    Authorship:Principal investigator  Grant type:Competitive

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  • The development of direct pulp capping materials using bilogical agent

    Grant number:24592868  2012.04 - 2015.03

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

    FUJII Masashi, SUZUKI Shigeki

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    Grant amount:\5330000 ( Direct expense: \4100000 、 Indirect expense:\1230000 )

    Various cytokines and growth factors induce wound healing during inflammatory responses. Wnts are known to enhance skin wound healing. In this study, we utilized gene-modified mice in which Wnts signal is prolonged during inflammatory responses. We experimentally exposed the molars of these mice to evoke pulpal tissue inflammation to analyze the importance of Wnt signal during pulpal tissue inflammation. The wound healing responses of pulpal tissues in the molars of these gene-modified mice were enhanced compared with that of control mice. The regenerated hard tissues in these gene-modified mice were morphologically bone-like structure and immunohistochemically dentin-like tissues. These results indicated the development of methods to enhance endogenous Wnt signal in pulpal tissues could be contribute for generating biological materials for direct pulp capping.

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  • Analysis of patients with gingival hyperplasia and hypertrichosis

    Grant number:23593059  2011 - 2013

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

    ARAKAWA Makoto, SUZUKI Shigeki, YAMASHITA Akiko, NISHIMURA Fusanori

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    Grant amount:\5460000 ( Direct expense: \4200000 、 Indirect expense:\1260000 )

    Recently, it has revealed that Cathepsin activities can invole with the onset of gingival hyperplasia. And some gingival hyperplasia patients are reported to have severe hypertrichosis. Therefore, the purpose of this study is to evaluate cathepsin activities of fibroblasts from patients with gingival hyperplasia and hypertrichosis and healthy person.
    The patients' cells showed decrease in Cathepsin-L activities, and increase in Cathepsin-B activities. Furthermore, Cathepsin-L knockout mice have abnormal turn over of hair follicle.
    From these results, it is suggested that decreased activity of Cathepsin may play a role to onset of hypertrichosis.

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  • Comprehensive analysis of the molecules up- or down- regulataed in dental pulp cells co-cultured with macrophages

    Grant number:23659889  2011 - 2013

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    NISHIMURA Fusanori, SUZUKI Shigeki, YAMASHITA Akiko, ABIKO Yoshimitsu

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    Grant amount:\3510000 ( Direct expense: \2700000 、 Indirect expense:\810000 )

    Irreversible pulpitis often accompanies intolerable pain. Hoever, pulp preservation is an ideal goal of dental treatment to avoid unwanted side effects such as tooth fracture. To save dental pulp, development of adhesive materials achieving no microleakage and controling dental pulp tissue inflammation are two essential factors. This study dealt with latter issue. The purpose of this study was 1) to establish in vitro pulpitis model, 2) to explore the reagent controlling pulp inflammation and the compound carrying such reagent, and 3) to analyze molcules up- or down- regulated under inflammatory conditions in pulp cells. All these approaches contribute to develop new strategy aiming the preservation of pulp tissues. We found the reason why pulpal inflammation expands in a short period and leads to tissue necrosis. These findings are important in our understanding the patho-physiology of dental pulp inflammation.

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  • 成体由来細胞を用いてのエナメル芽細胞樹立と歯胚再生法の確立.

    2011 - 2013

    日本学術振興会  科学研究費助成事業 若手研究(B) 

    鈴木茂樹

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    Authorship:Principal investigator  Grant type:Competitive

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  • 骨及び歯牙由来高度リン酸化タンパク質の硬組織再生への応用.

    2011

    科学技術振興機構  A-STEP探索研究成果展開事業 

    鈴木茂樹

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    Authorship:Principal investigator  Grant type:Competitive

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  • 象牙質形成におけるDSPP開裂のメカニズムと意義の解明.

    2009 - 2010

    日本学術振興会  科学研究費助成事業 研究活動スタート支援 

    鈴木茂樹

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    Authorship:Principal investigator  Grant type:Competitive

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  • Development of adhesive system with capacity of self-repair applied by Sr-CaPO4 complex

    Grant number:20592227  2008 - 2010

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

    SHIRAI Kenichi, SUZUKI Shigeki, NISHIMURA Fusanori, SHIBATA Satoru

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    Grant amount:\4030000 ( Direct expense: \3100000 、 Indirect expense:\930000 )

    The aim of study is to develop adhesive system with the capacity of self-repair applied by Sr-CaPO4 complex, in order
    1. to make of the best Sr-CaPO4 complex.
    2. to make of experimentally adhesive system included Sr-CaPO4 complex.
    3. to evaluate dentin re-calcification by Sr-CaPO4 complex and the experimental bonding system contained Sr-CaPO4 complex.
    As a result, dentin re-calcification was possessed though the Sr calcium phosphate complex was not more significant than Sr and the Ca unit.

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  • 栄養素と齲蝕感受性の関連性の解明

    Grant number:20659298  2008 - 2009

    日本学術振興会  科学研究費助成事業  挑戦的萌芽研究

    西村 英紀, 鈴木 茂樹

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    Grant amount:\3200000 ( Direct expense: \3200000 )

    DSPPは象牙質に最も多く存在する非コラーゲンタンパクであり、その遺伝子の翻訳産物は常にDSPとDPPの2つに開裂されて象牙質に沈着し、象牙質形成に重要な役割を果たす。しかしながら各々の生理的な機能は未だ不明な点が多い。そこでDSPPノックアウトマウスで、DSPのみをレスキューした、すなわちDPPのみを欠損したマウスの臼歯における表現型をH&E染色、X-ray、マイクロCT等を用いて解析した。DSPPノックアウトマウスの臼歯では、象牙前質と象牙質の境界である石灰化前線が不規則であり、また象牙質内に石灰化不全領域を認めた。一方、レスキューマウスでは、DSPPノックアウトマウスとは異なり、石灰化前線は歯髄腔に沿ってスムーズに存在し、象牙質内に石灰化不全領域を認めなかった。マイクロCTを用いて象牙質量(象牙質の体積量)及び象牙質密度(象牙質単位体積あたりのハイドロキシアパタイトの量)の測定を行った結果、DSPPノックアウトマウスでは象牙質量及び象牙質密度はDSPP+/-マウスと比較して共に有意に低下した。一方、レスキューマウスでは象牙質量はほぼDSPP+/-マウスと同レベルに戻ったものの、象牙質密度はDSPPノックアウトマウスと同様に低いままであった。DSPのみをレスキューすると象牙質量は大きく回復するものの、象牙質密度は変わらない事から、DSPは象牙質形成(前象牙質から象牙質への変換)に積極的に寄与し、DPPは主に象牙質形成後の象牙質成熟に寄与することが示唆された。以上から、栄養素の過剰あるいは欠乏よる影響としてDSPP遺伝子発現や産物のみでなくDSPPを開裂する未だ未解明の酵素の制御にも着目する必要があることを明らかにした。

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