https://scholars.lib.ntu.edu.tw/handle/123456789/204751
標題: | Stromal Cell-Derived Factor-1 Induces Matrix Metalloprotease-13 Expression in Human Chondrocytes | 作者: | CHIU, YUNG-CHENG YANG, RONG-SEN HSIEH, KUO-HSIEN FONG, YI-CHIN WAY, TZONG-DER LEE, TU-SHENG WU, HSI-CHIN FU, WEN-MEI TANG, CHIH-HSIN |
關鍵字: | STIMULATES FIBRONECTIN EXPRESSION;SIGNAL-REGULATED KINASES-1/2;RHEUMATOID-ARTHRITIS;CHEMOKINE RECEPTOR-4;PHOSPHOLIPASE-C;CARCINOMA-CELLS | 公開日期: | 2007 | 卷: | v.72 | 期: | n.3 | 起(迄)頁: | 695-703 | 來源出版物: | MOLECULAR PHARMACOLOGY | 摘要: | ABSTRACT The production of chemokine stromal cell-derived factor(SDF)-1 is significantly higher in synovial fluid of patients with osteoarthritis and rheumatoid arthritis. Matrix metalloproteinase (MMP)-13 may contribute to the breakdown of articular cartilage during arthritis. Here, we found that SDF-1 cultured human chondrocytes, as shown by reverse transcriptase- polymerase chain reaction, Western blot, and zymographic analysis. SDF-1 expression of CXCR4 receptor in human chondrocytes. CXCR4- neutralizing antibody , CXCR4-specific inhibitor [1-[[4-(1,4, 8,11- tetrazacyclotetradec-1-ylmethyl)phenyl] methyl]-1,4,8,11- tetrazacyclotetradecane (AMD3100)], or small interfering RNA against CXCR4 inhibited the SDF-1 induced increase of MMP- 13 expression. The transcriptional regulation of MMP-13 by SDF-1 phosphorylation of extracellular signal-regulated kinases ( ERK) and activation of the activator protein (AP)- 1 components of c-Fos and c-Jun. The binding of c- Fos and c - Jun to the activator protein (AP-1) element on the MMP-13 promoter and the increase in luciferase activity was enhanced by SDF-1 mutant of ERK2 or c-Fos and c-Jun antisense oligonucleotide inhibited the potentiating action of SDF-1 results provide evidence that SDF-1 activate ERK and the downstream transcription factors (c-Fos and c-Jun), resulting in the activation of AP-1 on the MMP- 13 promoter and contributing cartilage destruction during arthritis. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/92434 |
顯示於: | 醫學系 |
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