Attempt to establish chimeric osteoclast co-culture system and mechanistic analysis of osteoclast differentiation

• Project/Area Number: 15K10488
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Saitama Medical University
• Principal Investigator: SATO Kojiro 埼玉医科大学, 医学部, 准教授 (10372434)
• Research Collaborator: YANAGISAWA Maiko ; TACHIBANA Hideyuki ; AIZAKI Yoshimi ; YAZAWA Hiroaki ; ARAKI Yasuto ; MIMURA Toshihide
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 破骨細胞 / 骨芽細胞 / 滑膜由来線維芽細胞 / 破骨細胞分化因子 / 滑膜細胞 / 関節リウマチ / RANKL / M-CSF / OPG / 滑膜線維芽細胞

Outline of Final Research Achievements

Synovial fibroblasts cannot be substituted for osteoblasts in osteoclast differentiation. They apparently do not provide sufficient survival factor(s). They also do not provide enough RANKL. Instead, they produce a large amount of OPG. Thus, osteoclasts observed in the pannus may be dependent on RANKL from other sources, or may be differentiated by stimulation of cytokines other than RANKL, such as TNF-α and IL-6. Mouse osteoblasts also produce a large amount of OPG, which may function as a mechanism for preventing ectopic osteoclastogenesis.

Research Products

• [Journal Article] Altered gene expression profiles of histone lysine methyltransferases and demethylases in rheumatoid arthritis synovial fibroblasts. (2018)
  • Author(s): Araki Y, Aizaki Y, Sato K, Oda H, Kurokawa R, Mimura T.
  • Journal Title: Clinical and Experimental Rheumatology Volume: 印刷中
  • Peer Reviewed
• [Journal Article] A case of new-onset rheumatoid vasculitis becoming evident in the course of treatment for <i>Pneumocystis jirovecii</i> pneumonia (2017)
  • Author(s): Ikuma D, Yokota K, Sato K, Mimura T.
  • Journal Title: Japanese Journal of Clinical Immunology Volume: 40 Issue: 1 Pages: 78-82
  • DOI: 10.2177/jsci.40.78
  • NAID: 130005665661
  • ISSN: 0911-4300, 1349-7413
  • Peer Reviewed / Open Access
• [Journal Article] Porphyromonas gingivalis誘発TNF産生はRA樹状細胞で障害されている (2017)
  • Author(s): 佐藤 浩二郎
  • Journal Title: リウマチ科 Volume: 57 Pages: 63-67
• [Journal Article] Changes in the pattern of cytokine production from peripheral blood mononuclear cells in patients with rheumatoid arthritis treated with infliximab and their relation to plasma arginase activity (2016)
  • Author(s): Fumihiko Miyoshi, Kojiro Sato and Toshihide Mimura
  • Journal Title: International Journal of Rheumatic Diseases Volume: in press Issue: 11 Pages: 1907-1914
  • DOI: 10.1111/1756-185x.12864
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Histone Methylation and STAT-3 Differentially Regulate Interleukin-6-Induced Matrix Metalloproteinase Gene Activation in Rheumatoid Arthritis Synovial Fibroblasts. (2016)
  • Author(s): Araki Y, Tsuzuki Wada T, Aizaki Y, Sato K, Yokota K, Fujimoto K, Kim YT, Oda H, Kurokawa R, Mimura
  • Journal Title: Arthritis Rheumatol. Volume: 68 Issue: 5 Pages: 1111-23
  • DOI: 10.1002/art.39563
  • Peer Reviewed / Open Access
• [Journal Article] A case of systemic lupus erythematosus with multiple nodules in the bilateral lungs and vertebrae (2016)
  • Author(s): Takuma Tsuzuki Wada, Kojiro Sato, Toshihide Mimura
  • Journal Title: European Journal of Rheumatology Volume: 3 Issue: 1 Pages: 38-40
  • DOI: 10.5152/eurjrheum.2015.0026
  • Peer Reviewed
• [Journal Article] Immune complexes regulate bone metabolism through FcRγ signalling (2015)
  • Author(s): Negishi-Koga T, Gober HJ, Sumiya E, Komatsu N, Okamoto K, Sawa S, Suematsu A, Suda T, Sato K, Takai T, Takayanagi H.
  • Journal Title: Nat Commun Volume: 6 Issue: 1 Pages: 6637-6637
  • DOI: 10.1038/ncomms7637
  • Peer Reviewed / Open Access
• [Journal Article] Phosphoproteomic analysis of kinase-deficient mice reveals multiple TAK1 targets in osteoclast differentiation. (2015)
  • Author(s): Sumiya E, Negishi-Koga T, Nagai Y, Suematsu A, Suda T, Shinohara M, Sato K, Sanjo H, Akira S, Takayanagi H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 463 Issue: 4 Pages: 1284-90
  • DOI: 10.1016/j.bbrc.2015.06.105
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] A NOVEL HIERARCHICAL RELATIONSHIP BETWEEN INTERLEUKIN-17A AND INTERFERON-ALPHA IS INDICATED BY ANALYSIS OF MULTIPLE CYTOKINES IN THE SERUM OF ADULT-ONSET STILL’S DISEASE AND BEHCET’S DISEASE (2017)
  • Author(s): Sato Kojiro
  • Organizer: EULAR 2017 Congress Madrid
  • Int'l Joint Research
• [Presentation] キメラ培養系を用いたヒト破骨細胞培養系確立の試み (2016)
  • Author(s): 柳澤 麻依子
  • Organizer: 第60回日本リウマチ学会総会・学術集会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2016-04-21
• [Presentation] 破骨細胞分化におけるNFATc1 isoformにおける機能的差異の検討 (2016)
  • Author(s): 立花 秀介
  • Organizer: 第60回日本リウマチ学会総会・学術集会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2016-04-21
• [Book] リウマチ・膠原病治療薬ハンドブック (2018)
  • Author(s): 川畑仁人編集、三村俊英、佐藤浩二郎 他著
  • Total Pages: 238
  • Publisher: 文光堂
  • ISBN: 9784830620485
• [Book] リウマチ病学テキスト 改訂第２版 (2016)
  • Author(s): 日本リウマチ財団 日本リウマチ学会 編
  • Total Pages: 576
  • Publisher: 診断と治療社
• [Remarks] 埼玉医科大学リウマチ膠原病科
  • URL: http://www.saitama-med.ac.jp/uinfo/riumachi/index.html
• [Remarks] 埼玉医科大学リウマチ膠原病科ホームページ
  • URL: http://www.saitama-med.ac.jp/uinfo/riumachi/index.html