2006 Fiscal Year Final Research Report Summary
Pathological studies on the tissue destruction by metalloproteinases
| Project/Area Number |
16209015
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Keio University |
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Principal Investigator |
OKADA Yasunori Keio University, School of Medicine, Professor, 医学部, 教授 (00115221)
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| 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)
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| Project Period (FY) |
2004 – 2006
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| Keywords | ADAM / MMP / osteoarthritis / CD151 / tissue destruction / regeneration / knockout mice / wound healing |
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| 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.
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Research Products
(13 results)
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[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.
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Journal Title
Bichem. Biophys. Res. Commun (In press)
Description
「研究成果報告書概要(和文)」より
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[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
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Journal Title
Bichem. Biophys. Res. Commun. (In press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Proteinases and matrix degradation.2007
Author(s)
Okada Y.
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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
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[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.
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Journal Title
Nat. Med. 12
Pages: 1151-1159
Description
「研究成果報告書概要(和文)」より
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[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.
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Journal Title
Nat. Med. 12
Pages: 1151-1159
Description
「研究成果報告書概要(欧文)」より
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