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1996 Fiscal Year Final Research Report Summary

Studies on the destruction of articular cartilage by matrix metalloproteinases

Research Project

Project/Area Number 07457049
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionKanazawa University

Principal Investigator

OKADA Yasunori  Kanazawa University Cancer Research Institute, Dep.of Mol.Immunol., Professor, がん研究所, 教授 (00115221)

Project Period (FY) 1995 – 1996
KeywordsMatrix metalloproteinase / Rheumatoid arthritis / Osteoarthritis / Cartilage destruction / Degradation / Tissue inhibitor / Cytokine / Activation
Research Abstract

Matrix metalloproteinases (MMPs) are composed of at least 15 different molecules and their activities are strictly regulated by their common tissue inhibitors of metalloproteinases (TIMP-1,2,3,4). In the present studies, we have demonstrated that membrane-type 1 matrix metalloproteinase (MT1-MMP) is highly expressed in the human osteoarthritic cartilage showing a positive correlation with activation of proMMP-2 (progelatinase A). We have also revealed that MT1-MMP is an extracellular matrix (ECM) -degrading proteinase capable of digesting interstitial collagens and aggrecan as well as an activator of proMMP-2. In osteoarthritis and rheumatoid arthritis, cartilage matrix protein and SPARC were overexpressed, suggesting that it may be a tissue reaction secondary to the degradation of the ECM components by MMPs expressed in the cartilages. Actually, TGF-beta which stimulates ECM production in various mesenchymal cells was released after degradation of the TGF-beta/decorin complex by MMPs. To determine the production levels, sandwich enzyme immunoassays for MMP-7 and MMP-8 were also developed. Research projects on the mechanisms of MT1-MMP inhibition by TIMP-2 and expression of TIMP-1,2,3,4 in osteoarthritic and rheumatoid arthritic cartilages are now under way.

  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Ohuchi E.: "A ono-step sandwich enzyme immunoassay for human matrix metallo-proteinase 7 (matrilysin) using monoclonal antibodies." Clin. Chim. Acta. 244. 181-198 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura S.: "Enhancement of SPARC/osteonectin synthesis in articular cartilage. Its increased levels in synovial fluids from patients with rheumatoid arthritis and regulation by growth factors and cytokines in chondrocyte cultures." Arthritis Rheum.39. 539-551 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohuchi E.: "Membrane-type l-matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules." J. Biol. Chem.272. 2446-2451 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imai K.: "Degradation of decorin by matrix metalloproteinases. Identification of the cleavage sites, kinetic analyses and transforming growth factor-βl release." Biochem. J.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okimura A.: "Cartilage-matrix protein (CMP) synthesis is enhanced in arthritic cartilage." Arthritis Rheum.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imai K.: "Expression of membrane-type 1 matrix metalloproteinase and activation of progelatinase A in human osteoarthritic cartilage." Am. J. Pathol.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagase H.: "Proteinases and matrix degradation. Textbook of Rheumatology" W. B. Saunders Com., Philadelphia, 1904 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohuchi E., Azumano I., Yoshida S., Iwata K.and Okada Y.: "A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 7 (matrilysin) using monoclonal antibodies." Clin.Chim.Acta. 244. 181-198 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuki H., Fujimoto N., Iwata K., Knauper V., Okada Y.and Hayakawa T.: "A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 8 (neutrophil collagenase) using monoclonal antibodies" Clin.Chim.Acta. 244. 129-143 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura S., Kamihagi K., Satakeda H., Katayama M., Pan H., Okamoto H., Noshiro M., Takahashi K., Yoshihara Y., Shinmei M., Okada Y.and Kato Y.: "Enhancement of SPARC/osteonectin synthesis in articular cartilage. Its increased levels in synovial fluids from patients with rheumatoid arthritis and regulation by growth factors and cytokines in chondrocyte cultures." Arthritis Rheum. 39. 539-551 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito M., Masuda K., Ito Y., Akizawa T., Yoshioka M., K.Imai, Okada Y., Sato H.and Seiki M.: "Purification and refolding of recombinant human proMMP-7 (pro-matrilysin) expressed in Echelichia coil and its characterization." J.Biochem. 119. 667-673 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohashi K., Kawai R., Hara M., Okada Y., Tachibana S.and Ogura Y.: "Increased matrix metalloproteinases as possible cause of osseo-articular tissue destruction in long term hemodailysis and beta2-microglobulin amyloidosis." Virchows Archiv. 428. 37-46 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Imai K., Ohuchi E., Aoki T., Nomura H., Fujii Y., Sato H., Seiki M.and Okada Y.: "Membranetype matrix metalloproteinase 1 is a gelatinolytic enzyme and secreted in a complex with tissue inhibitor of metalloproteinases 2." Cancer Res. 56. 2707-2710 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato H., Takino T., Kinoshita T., Imai K., Okada Y., Stetler-Stevenson W.G.and Seiki M.: "Cell surface binding and activation of gelatinase A induced by expression of membrane-type matrix metalloproteinase-1 (MT-MMP-1)." FEBS Lett.385. 238-240 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohuchi E., Imai K., Fujii Y., SatoH., Seiki M.and Okada Y.: "Membrane-type 1-matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules." J.Biol.Chem.272. 2446-2451 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagase H.and Okada Y.: "Proteinases and matrix degradation. In Textbook of Rheumatology." Ed.by Kelley W.N., Harris E.D., Jr., Ruddy S.and Sledge C.B.5th edition, W.B.Saunders Company.Philadelphia. 323-341 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Imai K., Hiramatsu A., Fukushima D., Pierschbacher M.D.and Okada Y.: "Degradation of decorin by matrix metalloproteinases. Identification of the cleavage sites, kinetic analyzes and transforming growth factor-beta1 release." Biochem.J.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ueno H., Nakamura H., Inoue M., Imai K., Noguchi M., Sato H., Seiki M.and Okada Y.: "Expression and tissue localization of membrane-type 1,2 and 3 matrix metalloproteinases in human invasive breast carcinomas" Cancer Res.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okimura A., Okada Y., Makihira S., Pan H., Yu L., Tanne K., Imai K., Yamada H., Kawamoto T., Noshiro M., Yan W.and Kato Y.: "Cartilage-matrix protein (CMP) synthesis is enhanced in arthritic cartilage." Arthritis Rheum. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Imai K., Ohta S., Matsumoto T., Fujimoto N., Sato H., Seiki M.and Okada Y.: "Expression of membrane-type 1 matrix metalloproteinase and activation of progelatinase A in human osteoarthritic cartilage." Am.J.Pathol. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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