• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2006 Fiscal Year Final Research Report Summary

Pathological studies on the tissue destruction by metalloproteinases

Research Project

Project/Area Number 16209015
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionKeio University

Principal Investigator

OKADA Yasunori  Keio University, School of Medicine, Professor, 医学部, 教授 (00115221)

Co-Investigator(Kenkyū-buntansha) IKEDA Eiji  Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (30232177)
FUJII Yutaka  University of Fukui Faculty of Medical Science, Biochemistry and Bio informative Sciences, Associate Professor, 化学, 助教授 (80211522)
Project Period (FY) 2004 – 2006
KeywordsADAM / MMP / osteoarthritis / CD151 / tissue destruction / regeneration / knockout mice / wound healing
Research Abstract

CD151, a member of the tetraspanin family, was co-localized with MMP-7 in the chondrocytes of osteoarthritic cartilage, showing positive correlations of the CD151 immunoreactivity with Mankin scores and degree of chondrocyte cloning. Co-localization of the molecules in osteoarthritic chondrocytes resulted in pericellular activation of proMMP-7. These data suggest that CD151 is implicated in the destruction of articular cartilage and chondrocyte regeneration through the proMMP-7 activation in osteoarthritis. Among the proteinase-type ADAM8, 9, 10, 12, 15, 17, 20, 21, 28 and 30, ADAM12 was selectively expressed in the osteoarthritic chondrocytes and its immunoreactivity in osteoarthritic cartilage showed a direct correlation with degree of chondrocyte cloning. Cell proliferation and ADAM12 expression were induced by the chondrocyte treatment with TGF-β, and cell proliferation was inhibited with ADAM inhibitor, neutralizing anti-ADAM12 antibody or siRNA for ADAM12. The findings that ADAM 12 releases IGF-I from the IGF-PIGF-BP complex through digestion of IGF-BP suggest that ADAM12 is involved in chondrocyte proliferation through enhanced availability of IGF-I in osteoarthritis. Wound healing processes were analyzed in wild type, MMP-13-/-, MMP-9-/-and MMP-9/13-/-mice and compared each other. Re-epithelialization was delayed in MMP-9/13-/-, MMP-9-/-and MMP-13-/-mice compared with wild type mice in this order, and angiogenesis in the granulation tissue was retarded in MMP-9/13-/-and MMP-13-/-mice. These data suggest the important roles of both MMP-9 and MMP-13 in re-epithelialization and of MMP-13 in angiogenesis.

  • Research Products

    (13 results)

All 2007 2006

All Journal Article (12 results) Book (1 results)

  • [Journal Article] Joint diseases and matrix metalloproteinases : A role for MMP-132007

    • Author(s)
      Takaishi H., Kimura T., Dalal S., Okada Y., D'Armiento J.
    • Journal Title

      Cur. Pharma. Biotechonol. (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Impaired bone fracture healing in matrix metalloproteinase 13 (MMP-13) deficient mice.2007

    • Author(s)
      Kosaki N., Takaishi H, Kamekura S., Kimura.T., Okada Y., Minqi L., Amizuka N., Chung U., Nakamura.K., Kawaguchi H., Toyama Y., D'Armiento J.
    • Journal Title

      Bichem. Biophys. Res. Commun (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Serum levels of matrix metalloproteinase-3 (stromelysin 1) for monitoring synovitis in rheumatoid arthritis.2007

    • Author(s)
      Kobayashi A., Okazaki S., Enomoto H., Shiomi T., Obata K., Okada Y.
    • Journal Title

      Arch. Pathol. Lab. Med. (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Joint diseases and matrix metalloproteinases : A role for MMP-13.2007

    • Author(s)
      Takaishi H., Kimura T., Dalai S., Okada Y, D'Armiento J
    • Journal Title

      Cur. Pharma. Biotechonol. (In press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Impaired bone fracture healing in matrix metalloproteinase 13 (MMP-13) deficient mice.2007

    • Author(s)
      Kosaki N., Takaishi H., Kamekura S., Kimura T., Okada Y, Minqi L., Amizuka N., Chung U., Nakamura K., Kawaguchi H., Toyama Y, D'Armiento J
    • Journal Title

      Bichem. Biophys. Res. Commun. (In press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Serum levels of matrix metalloproteinase-3 (stromelysin 1) for monitoring synovitis rheumatoid arthritis.2007

    • Author(s)
      Kobayashi A., Okazaki S., Enomoto EL, Shiomi T., Obata K., Okada Y
    • Journal Title

      Arch. Pathol. Lab. Med. (In press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Proteinases and matrix degradation.2007

    • Author(s)
      Okada Y.
    • Journal Title

      Kelley's Textbook of Rheumatology. Ed. by Harris E. D., Jr., Budd R. C., Ruddy S., Genovese M.C., Firestein G S. and Sargent J. S. 8th edition, Elsevier Saunders. Philadelphia (In press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Tetraspanin CD151 is expressed in osteoarthritic cartilage and is involved in pericellular activation of zymogen of matrix metalloproteinase-7 (matrilysin 1) in osteoarthritic cartilage.2006

    • Author(s)
      Fujita Y., Shiomi T., Yanagimoto S., Matsumoto H., Toyama Y., Okada Y
    • Journal Title

      Arthritis Rheum. 54

      Pages: 3233-3243

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differential expression of WNTs and FRPs in the synovium of rheumatoid arthritis and osteoarthritis.2006

    • Author(s)
      Imai K, Morikawa M, D'Arminento J, Matsumoto H, Komiya K, Okada Y.
    • Journal Title

      Biochem. Biophys. Res. Commun. 345

      Pages: 1615-1620

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Chondromodulin-I maintain cardiac valvular function by preventing angiogenesis.2006

    • Author(s)
      Yoshioka M, Yuasa.S., Matsumura K', Shiomi.T., Shukunami C, Okaqa Y., Mukai M., Shin H., Yozu R., Sata M., Ogawa S, Hiraki Y., Fukuda K.
    • Journal Title

      Nat. Med. 12

      Pages: 1151-1159

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Tetraspanin CD151 is expressed in osteoarthritic cartilage and is involved in pericellular activation of zymogen of matrix metalloproteinase-7 (matrilysin 1) in osteoarthritic cartilage.2006

    • Author(s)
      Fujita Y, Shiomi T., Yanagimoto S., Matsumoto H., Toyama Y., Okada Y.
    • Journal Title

      Arthritis Rheum. 54

      Pages: 3233-3243

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Chondromodulin-I maintain cardiac valvular function by preventing angiogenesis.2006

    • Author(s)
      Yoshioka M., Yuasa S., Matsumoto K., Shiomi T., Shukunami C, Okada Y, Mukai M., Shin H., Yozu R., Sata M., Ogawa S., Hiraki Y, Fukuda K.
    • Journal Title

      Nat. Med. 12

      Pages: 1151-1159

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Proteinases and matrix degradation.(Ed. by Harris E. D., Jr., Budd R. C., Ruddy S., Genovese M.C., Firestein G. S. and Sargent J. S. 8th edition.)2007

    • Author(s)
      Okada Y.
    • Publisher
      Kelley's Textbook of Rheumatology. Elsevier Saunders. Philadelphia.(In press)
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2008-05-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi