Studies on the destruction of articular cartilage by matrix metalloproteinases

基质金属蛋白酶破坏关节软骨的研究

基本信息

  • 批准号:
    07457049
  • 负责人:
  • 金额:
    $ 4.93万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    1995
  • 资助国家:
    日本
  • 起止时间:
    1995 至 1996
  • 项目状态:
    已结题

项目摘要

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.
基质金属蛋白酶(Matrix metalloproteinases,MMPs)由至少15种不同的分子组成,其活性受其共同的组织金属蛋白酶抑制剂(tissue inhibitor of metalloproteinases,TIMP-1,2,3,4)的严格调控。在本研究中,我们已经证明,膜型1基质金属蛋白酶(MT 1-MMP)是高表达的人骨关节炎软骨显示与MMP-2(明胶酶A)的激活呈正相关。我们还发现,MT 1-MMP是一种细胞外基质(ECM)降解蛋白酶,能够消化间质胶原和聚集蛋白聚糖以及proMMP-2的激活剂。在骨关节炎和类风湿性关节炎中,软骨基质蛋白和ECM过度表达,表明这可能是继发于软骨中表达的MMP降解ECM组分的组织反应。实际上,在各种间充质细胞中刺激ECM产生的TGF-β在TGF-β/核心蛋白聚糖复合物被MMP降解后释放。为了确定生产水平,还开发了MMP-7和MMP-8的夹心酶免疫测定法。TIMP-2对MT 1-MMP的抑制机制以及TIMP-1、2、3、4在骨关节炎和类风湿关节炎软骨中的表达的研究正在进行中。

项目成果

期刊论文数量(19)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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 (199
Ohashi K.、Kawai R.、Hara M.、Okada Y.、Tachibana S.和 Ogura Y.:“基质金属蛋白酶的增加可能是长期血液透析和 β2-微球蛋白淀粉样变性中骨关节组织破坏的原因。”
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    0
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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)
Okimura A.、Okada Y.、Makihira S.、Pan H.、Yu L.、Tanne K.、Imai K.、Yamada H.、Kawamoto T.、Noshiro M.、Yan W.和 Kato Y.:“软骨
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    0
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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)
Imai K.:“基质金属蛋白酶对核心蛋白聚糖的降解。切割位点的鉴定、动力学分析和转化生长因子-β1 释放。Biochem J.(出版中)。”
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    0
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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)
Matsuki H.、Fujimoto N.、Iwata K.、Knauper V.、Okada Y. 和 Hayakawa T.:“使用单克隆抗体对人基质金属蛋白酶 8(中性粒细胞胶原酶)进行一步夹心酶免疫测定” Clin.Chim.Acta
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    0
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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)
Ito M.、Masuda K.、Ito Y.、Akizawa T.、Yoshioka M.、K.Imai、Okada Y.、Sato H. 和 Seiki M.:“重组人 proMMP-7(pro-matrilysin)的纯化和重折叠
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OKADA Yasunori其他文献

OKADA Yasunori的其他文献

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{{ truncateString('OKADA Yasunori', 18)}}的其他基金

Pathological study on metalloproteinases in tissue remodeling under pathological conditions
病理条件下金属蛋白酶参与组织重塑的病理学研究
  • 批准号:
    24249022
  • 财政年份:
    2012
  • 资助金额:
    $ 4.93万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Study of integral transformations in hyperfunctions and differential operators of infinite order
超函数积分变换和无限阶微分算子的研究
  • 批准号:
    22540173
  • 财政年份:
    2010
  • 资助金额:
    $ 4.93万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Functional analyses and regulation of the metabolism of tissue microenvironmental factors by metalloproteinases
金属蛋白酶对组织微环境因子代谢的功能分析和调节
  • 批准号:
    19109004
  • 财政年份:
    2007
  • 资助金额:
    $ 4.93万
  • 项目类别:
    Grant-in-Aid for Scientific Research (S)
Pathological studies on the tissue destruction by metalloproteinases
金属蛋白酶组织破坏的病理学研究
  • 批准号:
    16209015
  • 财政年份:
    2004
  • 资助金额:
    $ 4.93万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Study of global solutions to Fuchsian equations and local solutions to linear PDE
Fuchsian方程全局解和线性偏微分方程局部解的研究
  • 批准号:
    15540156
  • 财政年份:
    2003
  • 资助金额:
    $ 4.93万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Research concerning Privacy Protection Principles about Data Transfer from EU to the United States
欧盟至美国数据传输隐私保护原则研究
  • 批准号:
    14520022
  • 财政年份:
    2002
  • 资助金额:
    $ 4.93万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Regulation of MT1-MMP gene expression by HMGI-C
HMGI-C对MT1-MMP基因表达的调控
  • 批准号:
    11694311
  • 财政年份:
    1999
  • 资助金额:
    $ 4.93万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Molecular Pathology of Cartilage destruction in Rheumatoid Arthritis
类风湿关节炎软骨破坏的分子病理学
  • 批准号:
    10470051
  • 财政年份:
    1998
  • 资助金额:
    $ 4.93万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Analyzes on ECM metabolism in transgenic and knockout mice
转基因和基因敲除小鼠 ECM 代谢分析
  • 批准号:
    08044262
  • 财政年份:
    1996
  • 资助金额:
    $ 4.93万
  • 项目类别:
    Grant-in-Aid for international Scientific Research

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成纤维细胞亚群之间的衰老差异是否可以解释随着年龄的增长,类风湿关节炎和骨关节炎的进展加快?
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