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破骨細胞形成の分子機構

Research Project

Project/Area Number 09877284
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionMie University

Principal Investigator

伊藤 康彦  三重大学, 医学部, 教授 (00022872)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Keywords破骨細胞 / FRP-1 / CD98 / 血液単球 / c-src / Protein Kinase / マウスFRP-1 / Protein Tyrosine Kinase
Research Abstract

抗FRP-1抗体による破骨細胞形成機構に関して以下の事を明らかにした。
(a)血液細胞の中では、FRP-1は単球に選択的に存在する。Tリンパ球を活性化すると、FRP-1は発現してくる。(b)血液単球に抗FRP-1抗体(mAb 6-1-13)を作用させると、数時間以内に細胞凝集が24時間以内に細胞融合が出現する。(c)抗FRP-1抗体によって誘導された融合細胞は、培養するに従って、大きくなり、多核巨細胞を形成する。(d)多核巨細胞は、TRAP陽性、カルシトニン-レセプター陽性及び骨融解能を示す様になり、破骨細胞へと分化した。(e)血液単球に抗FRP-1抗体(mAb6-1-13)を作用させると、破骨細胞へと分化とその増殖に関与すると予想される遺伝子のうち、c-srcmRNAが特異的に誘導されてくることを見い出した。c-src蛋白も発現する様になった。(f)抗FRP-1抗体の一つ(HBJ127)はmAb 6-1-13による多核巨細胞形成や破骨細胞形成を阻害した。(g)HBJ127はmAb 6-1-13によるc-src発現誘導も阻害した。(h)FRP-1システムはc-src発現誘導を介して破骨細胞形成に強く関与していることが推測された。

Report

(2 results)
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Shigeomi Higuchi: "Induction of human osteoclast-like cells by treatment of blood monocytes with anti-fusion regulatory protein-1/CD98 monoclonal antibodies." Journal of Bone and Mineral Research. Vol.13. 44-49 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masato Tsurudome: "Identification of regions on the fusion protein of human parainfluenza type 2 virus which are required for haemagglutinin-neuraminidase proteins to promote cell fusion." Journal of General Virology. Vol.79. 279-289 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hideki Tsumura: "Mouse alloantigen Ly10 is identical to murine fusion regulatory protein-1(mFRP-1)/4F2/CD98:Aberrant expression of mFRP-1/Ly10 alltypes in cells derived from CDE1 mice." Cellular Immunology. Vol.184. 153-160 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masato Tsurudome: "Primary structure of the light chain of FRP-1/CD98/4F2 predicts a protein with multiple transmembrane domains that is almost identical to the amino acid transporter E16." Journal of Immunology. Vol.162. in the press (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Murphy,Y.: "A functional antigenomic promoter for the paramyxovirus simian virus 5 requires proper spacing between an essential internal segment and the 3' terminus" J.Virology. Vol.72. 10-19 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hideki Tsumura: "Isolatron and Characterization of Monoclonal Antibodies Directed Agains Murine FRP-1/CD98/4F2 Heavy Chain:" Immunology and Cell Biology. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Kousuke Okamoto: "An anti-fusion regulatory protein-1 monoclonal antibody suppresses human parainfluenza virus type 2-induced cell fusion." Journal of General Virology. Vol.78. 83-89 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kousuke Okamoto: "Paramyxovirus-induced syncytium cell formation is suppressed by a dominant negative fusion regulatory protein-1(FRP-1)/CD98 mutated construct." Journal of General Virology. Vol.78. 775-783 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kousuke Okamoto: "Enhancement of human parainfluenza virus-induced cell fusion by pradimicin, a low molecular weight mannose-binding antibiotic." Medical Microbiology and Immunology. Vol.186. 101-108 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shigeru Suga: "Human immunodeficiency virus type-1 envelope glycoprotein gp120 induces expression of fusion regulatory protein(FRP)-1/CD98 on CD4_+ T cells." Medical Microbiology and Immunology. Vol.186. 237-243 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Machiko Nishio: "Human parainfluenza virus type 2 phosphoprotein : Mapping of monoclonal antibody epitopes and location of the multimerization domain." Journal of General Virology. Vol.78. 1303-1308 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Morihiro Ito: "Role of a single amino acid at the amino terminus of the simian virus 5 F2 subunit in syncytium formation." Journal of Virology. Vol.71. 9855-9858 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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