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The molecular target of heat shock protein in bone metabolism

Research Project

Project/Area Number 15K10487
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionNagoya City University

Principal Investigator

Otsuka Takanobu  名古屋市立大学, 大学院医学研究科, 教授 (10185316)

Co-Investigator(Kenkyū-buntansha) 水谷 潤  名古屋市立大学, 大学院医学研究科, 准教授 (70326156)
鈴木 伸幸  名古屋市立大学, 大学院医学研究科, 助教 (50551230)
小澤 修  岐阜大学, 大学院医学系研究科, 教授 (90225417)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥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骨芽細胞 / Heat shock protein / HSP27 / HSP22 / 骨代謝 / 骨粗鬆症 / osteoblast / heat shock protein / PDGF-BB / migration / TGF-β
Outline of Final Research Achievements

Heat shock proteins (HSPs) are induced by a variety of physiological and environmental stresses, such as heat. As molecular chaperones, HSPs facilitate the refolding of unfolded proteins. However, the details behind the HSP-mediated effects on osteoblasts remain to be clarified. In the present study, in order to investigate the exact mechanism of HSPs in osteoblasts, we explored the molecular targets of HSP27 and HSP22 using osteoblast-like MC3T3-E1 cells. Our results strongly suggest that HSP27 functions as a negative regulator in the PDGF-BB-stimulated migration of osteoblasts, and the suppressive effect is amplified by the phosphorylation state of HSP27. HSP22 functions as a negative regulator in the TGF-β-stimulated migration of osteoblasts via suppression of the Smad-dependent pathway. In addition, HSP22 interacts with mTOR and regulates TNF-α-induced IL-6 synthesis in osteoblasts.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (6 results)

All 2018 2017 2016

All Journal Article (6 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 3 results)

  • [Journal Article] Association of HSP22 with mTOR in osteoblasts: regulation of TNF-α-stimulated IL-6 synthesis2018

    • Author(s)
      Sakai Go、Tokuda Haruhiko、Yamamoto Naohiro、Matsushima-Nishiwaki Rie、Fujita Kazuhiko、Kawabata Tetsu、Kozawa Osamu、Otsuka Takanobu
    • Journal Title

      FEBS Letters

      Volume: 592 Issue: 7 Pages: 1202-1210

    • DOI

      10.1002/1873-3468.13028

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Heat shock protein 70 negatively regulates TGF-β-stimulated VEGF synthesis via p38 MAP kinase in osteoblasts.2017

    • Author(s)
      Sakai G, Tokuda H, Fujita K, Kainuma S, Kawabata T, Matsushima-Nishiwaki R, Kozawa O, Otsuka T.
    • Journal Title

      Cell. Physiol. Biochem.

      Volume: 44 Issue: 3 Pages: 1133-1145

    • DOI

      10.1159/000485418

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Suppression by HSP90 inhibitors of BMP-4-stimulated osteoprotegerin synthesis in osteoblasts: Attenuation of p70 S6 kinase2017

    • Author(s)
      Kawabata Tetsu、Otsuka Takanobu、Fujita Kazuhiko、Kainuma Shingo、Yamamoto Naohiro、Kuroyanagi Gen、Sakai Go、Matsushima-Nishiwaki Rie、Kozawa Osamu、Tokuda Haruhiko
    • Journal Title

      Molecular Medicine Reports

      Volume: 16 Issue: 6 Pages: 8507-8512

    • DOI

      10.3892/mmr.2017.7639

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Heat shock protein 27 (HSPB1) suppresses the PDGF-BB-induced migration of osteoblasts2017

    • Author(s)
      Kainuma Shingo、Tokuda Haruhiko、Yamamoto Naohiro、Kuroyanagi Gen、Fujita Kazuhiko、Kawabata Tetsu、Sakai Go、Matsushima-Nishiwaki Rie、Kozawa Osamu、Otsuka Takanobu
    • Journal Title

      International Journal of Molecular Medicine

      Volume: 40 Issue: 4 Pages: 1057-1066

    • DOI

      10.3892/ijmm.2017.3119

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] HSP90 inhibitors potentiate PGF2α-induced IL-6 synthesis via p38 MAP kinase in osteoblasts2017

    • Author(s)
      Fujita Kazuhiko、Tokuda Haruhiko、Kuroyanagi Gen、Yamamoto Naohiro、Kainuma Shingo、Kawabata Tetsu、Sakai Go、Matsushima-Nishiwaki Rie、Kozawa Osamu、Otsuka Takanobu
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 5 Pages: e0177878-e0177878

    • DOI

      10.1371/journal.pone.0177878

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Heat shock protein 22 (HSPB8) limits TGF-β-stimulated migration of osteoblasts.2016

    • Author(s)
      Yamamoto N, Tokuda H, Kuroyanagi G, Kainuma S, Matsushima-Nishiwaki R, Fujita K, Kozawa O, Otsuka T.
    • Journal Title

      Mol Cell Endocrinol

      Volume: 436 Pages: 1-9

    • DOI

      10.1016/j.mce.2016.07.011

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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