Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/3940
標題: Cyr61 Induces Matrix Metalloprotease-13 Expression in Human Chondrocytes
探討Cyr61 刺激對人類軟骨細胞分泌基質金屬蛋白酶之作用
作者: 張家豪
Chang, Chia-Hao
關鍵字: Cyr61
基質金屬蛋白酶軟骨細胞
MMP-13
osteoarthritis
關節炎
出版社: 生醫工程研究所
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摘要: Abstract Cyr61 (CCN1) is a proinflammatory cytokine and is involved in cell adhesion, proliferation, and differentiation. Cyr61 is overexpressed in synovial tissue and fibroblast-like synovial cells derived from rheumatoid arthritis (RA) patients. Matrix metalloproteinase (MMP)-13 plays a role in the breakdown of articular cartilage during arthritis. Here, we found that Cyr61 increase the secretion of MMP-13 in cultured human chondrocytes and chondrosarcoma cell line SW-1353, as shown by Real-Time PCR reaction, Western blot, and zymographic analysis. Cyr61 also increased the surface expression of integirn αvβ3 receptor in human chondrocytes and SW-1353. RGD peptide, αvβ3 monoclonal antibody but not RAD peptide inhibited the Cyr61-induced increase MMP-13 upregulation in SW-1353. The transcriptional regulation of MMP-13 by Cyr61 was mediated by phosphorylation of focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K)/AKT pathway and Nuclear Factor-KappaB (NF-κB). The binding of p65/p50 to the NF-κB element on the MMP-13 promoter and the increase in luciferase activity was enhanced by Cyr61. Cotransfection with dominant-negative mutant of FAK, p85, AKT, IKKα, IKKβ and FAK si-RNA inhibited the potentiating action of Cyr61 on MMP-13 promoter activity. Taken together, our results provide evidence that Cyr61 acts through integrin αvβ3 to activate PI3K/AKT pathway, resulting in the activation of NF-κB on the MMP-13 promoter and contributing cartilage destruction during arthritis.
URI: http://hdl.handle.net/11455/3940
其他識別: U0005-0808201023495800
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-0808201023495800
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