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Analysis of signaling pathways involved in polarization of osteoclasts.

Research Project

Project/Area Number 05454507
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionShowa University

Principal Investigator

TAKAHASHI Naoyuki  School of Dentistry, Showa University Associate Professor, 歯学部, 助教授 (90119222)

Co-Investigator(Kenkyū-buntansha) SASAKI Takahisa  School of Dentistry, Associate Professor, 歯学部, 助教授 (50129839)
UDAGAWA Nobuyuki  School of Dentistry, Assistant, 歯学部, 助手 (70245801)
SUDA Tatsuo  School of Dentistry, Professor, 歯学部, 教授 (90014034)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1994: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1993: ¥3,700,000 (Direct Cost: ¥3,700,000)
Keywordsosteoclast / ruffled border / clear zone / podosme / calcitonin / p60^<c-src> / PI-3 kinase / small GTP binding protein rho / Pl-3キナーゼ / op / opマウス / oc / ocマウス / c-src / Focal adhesion kinase / ポドソーム形成 / 吸収窩
Research Abstract

(1) We have previously established a culture system for examining osteoclast formation. In the present study, a new resorption assay system was also established using osteoclast-like cells formed in vitro. Therefore, it is now possible to examine the effect of various compounds on the recruitment of osteoclasts and pit formation by the same osteoclasts in a series of experiments.
(2) Using op/op mouse-derived osteoblastic cells, we found that M-CSF is indispensable not only for proliferation of osteoclast precursors but also for their differentiation into osteoclasts.
(3) When osteoclasts were placed on dentine slices or plastic dishes, they formed the ringed structure of podosomes (actin rings). The ringed structure is shown to correspond to clear zones of bone resorbing osteoclasts. The Formation and disruption of the actin ring were correlated well with pit forming activity of osteoclasts.
(4) It was shown that signaling pathways meditated by p60^<c-src>, PI-3 kinase, focal adhesion kinase and small GTP binding protein, rho, are essentially involved in actin ring formation by osteoclasts. It has been proposed that calcitonin receptors are coupled to the pathways associated with both protein kinase A and protein kinase C.We examined the signaling pathway of calcitonin action in osteoclast-like cells. We found that calcitonin-induced dramatic alteration in the cytoskeleton is mainly mediated by the protein kinase A pathway.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Nakamura,I.et al.: "Wortmannin,a specific inhibitor of phosphatidylinosi-tol-3 kinase,bolcks osteoclastic bone resorption." FEBS Lett.in press. (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahashi,N.et al.: "Regulation of osteoclast function by calcitonin and its related peptides" Osteoporosis Japan. 3. 17-29 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Wada,S.et al.: "Glucocorticoid regulation of calcitonin receptor in mouse osteoclast-like multinucleated cells." J Bone Miner.Res.9. 1705-1712 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nishihara,T.et al.: "Membrane-associated interleukin-1 promotes osteoclast-like cell formation in vitro." Bone Miner.25. 15-24 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahashi,N.et al.: "Postmitoic osteoclast precursors are mononuclear cells which express macrophage-associated phenotypes." Dev.Biol.163. 212-221 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tamura,T.et al.: "Soluble interleukin-6 receptor triggers osteoclast formation by interleukin-6" Proc.Natl.Acad.Sci.USA. 90. 11924-11928 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakamura, I.et al.: "Wortmannin, a specific inhibitor of phosphatidylinositol-3 kinase, blocks osteoclastic bone resorption" FEBS Lett.(in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahashi, N.et al.: "Regulation of osteoclast function by calcitonin" Osteoporosis Japan. 3. 17-29 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Wada, S.et al.: "Glucocorticoid regulation of calcitonin receptor in mouse osteoclast-like multinucleated cells." J.Bone Miner Res.9. 1705-1712 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nishihara, T.et al.: "Membrane-associated interleukin-1 promotes osteoclast-like cell formation in vitro." Bone Miner.91, 25. 257-263 , 15-24 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahashi, N.et al.: "Postmitotic osteoclast precursors are mononuclear cells which express macrophage-associated phenotypes." Developmental Biol.163. 212-221 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tamura, T.et al.: "Soluble Interleukin-6 receptor triggers osteoclast formation by interleukin-6." Proc.Natl.Acad.Sci.USA. 90. 11924-11928 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakamura,I.et al.: "Wortmannin,a specific inhibitor of phosphatidylinositol-3 kinase,bolcks osteoclastic bone resorption." FEBS Lett.in press. (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tanaka,S.et al.: "Possible involvement of focal adhesion kinase,p125^<FAK>,in osteoclastic bone resorption." J.Cell Biochem.in press. (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takahashi,N.et al.: "Regulation of osteoclst function by calcitonin and its related peptides." Osteoporosis Japan. 3. 17-29 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Wada,S.et al.: "Glucocorticoid regulation of calcitonin receptor in mouse osteoclast-like multinucleated cells." J.Bone Miner.Res.9. 1705-1712 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nishihara,T.et al.: "Membrane-associated interleukin-1 promotes osteoclast-like cell formation in vitro." Bone Miner.25. 15-24 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takahashi,N.et al.: "Postmitotic osteoclast precursors are mononuclear cells which express macrophage-associated phenotypes." Dev.Biol.163. 212-221 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tanaka,S.et al.: "Macrophage colony-stimulating tactor (M-SCF) is indespesable for both proliferation and differentiation of osteoclast progenitors." J.Clin.Invest.91. 257-263 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tamura,T.et al.: "A new resorption assay with mouse osteoclast-like multinucleated cells formed invitro." J.Bone Miner.8. 953-960 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tamura,T.et al.: "Soluble interleukin-6 receptor tirggers osteoclast formation by interleukin 6." Proc.Natl.Acad.Sci.USA. 90. 11924-11928 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takahashi,N.et al.: "Postmitotic osteoclast precursors are mononuclear cells which express macrophage-associated phenotypes." Dev.Biol.(in press). (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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