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Pathological studies on the tissue destruction by metalloproteinases

金属蛋白酶组织破坏的病理学研究

基本信息

批准号：
16209015
负责人：
OKADA Yasunori
金额：
$ 31.95万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

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.

CD151是Tetraspanin家族的成员，与基质金属蛋白酶-7共定位于骨关节炎软骨细胞中，CD151的表达与软骨细胞的Mankin评分和克隆程度呈正相关。这些分子在骨关节炎软骨细胞中的共同定位导致了原基质金属蛋白酶-7在细胞周围的激活。提示CD151可能通过激活原基质金属蛋白酶-7参与骨关节炎关节软骨的破坏和软骨细胞的再生。在ADAM8、9、10、12、15、17、20、21、28和30中，ADAM12选择性表达于骨关节炎软骨细胞，其在骨关节炎软骨中的免疫反应与软骨细胞克隆程度呈正相关。转化生长因子-β可促进软骨细胞增殖和ADAM12的表达，而ADAM抑制剂、抗ADAM12抗体或ADAM12的小干扰RNA可抑制细胞增殖。ADAM12通过消化IGF-BP从IGF-PIGF-BP复合体释放IGF-I的研究结果表明，ADAM12通过增加骨关节炎中IGF-I的可获得性而参与软骨细胞的增殖。对野生型、MMP13-/-、MMP9-/-和MMP9/13-/-小鼠的伤口愈合过程进行了分析和比较。与野生型小鼠相比，MMP9/13-/-、MMP9-/-和MMP13-/-小鼠的再上皮化时间依次延迟，肉芽组织中的血管生成也受到抑制。这些数据表明，基质金属蛋白酶-9和基质金属蛋白酶-13在再上皮化和基质金属蛋白酶-13在血管生成中都起着重要的作用。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

7th edition, Elsevier Saunders. Philadelphia

第七版，爱思唯尔桑德斯。

DOI：
发表时间：
2005
期刊：
影响因子：
0
作者：
S.Inomata;N.Shijubo;S.Kon;M.Maeda;G.Yamada;N.Sato;S.Abe;T.TUede;Okada Y.
通讯作者：
Okada Y.

Impaired bone fracture healing in matrix metalloproteinase 13 (MMP-13) deficient mice.

基质金属蛋白酶 13 (MMP-13) 缺陷小鼠的骨折愈合受损。

DOI：
发表时间：
2007
期刊：
Bichem. Biophys. Res. Commun. (In press)
影响因子：
0
作者：
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
通讯作者：
D'Armiento J

Serum levels of matrix metalloproteinase-3 (stromelysin 1) for monitoring synovitis in rheumatoid arthritis.

用于监测类风湿性关节炎滑膜炎的基质金属蛋白酶 3（溶基质素 1）的血清水平。