https://scholars.lib.ntu.edu.tw/handle/123456789/563772
標題: | Stromal cell-derived factor-1 induces matrix metalloprotease-13 expression in human chondrocytes | 作者: | Chiu Y.-C. RONG-SEN YANG Hsieh K.-H. Fong Y.-C. Way T.-D. Lee T.-S. Wu H.-C. WEN-MEI FU Tang C.-H. |
公開日期: | 2007 | 卷: | 72 | 期: | 3 | 起(迄)頁: | 695-703 | 來源出版物: | Molecular Pharmacology | 摘要: | 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-1α increased the secretion of MMP-13 in cultured human chondrocytes, as shown by reverse transcriptase-polymerase chain reaction, Western blot, and zymographic analysis. SDF-1α also increased the surface 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-1α-induced increase of MMP-13 expression. The transcriptional regulation of MMP-13 by SDF-1α was mediated by 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-1α. Cotransfection with dominant-negative mutant of ERK2 or c-Fos and c-Jun antisense oligonucleotide inhibited the potentiating action of SDF-1α on MMP-13 promoter activity. Taken together, our results provide evidence that SDF-1α acts through CXCR4 to 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. Copyright ? 2007 The American Society for Pharmacology and Experimental Therapeutics. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-34548316592&doi=10.1124%2fmol.107.036541&partnerID=40&md5=f6bb26c6772297ee79e624632aac3297 https://scholars.lib.ntu.edu.tw/handle/123456789/563772 |
ISSN: | 0026-895X | DOI: | 10.1124/mol.107.036541 | SDG/關鍵字: | 1,1' [1,4 phenylenebis(methylene)]bis(1,4,8,11 tetraazacyclotetradecane); 2 (2 amino 3 methoxyphenyl)chromone; 2 morpholino 8 phenylchromone; 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole; anthra[1,9 cd]pyrazol 6(2h) one; chemokine receptor CXCR4; collagenase 3; messenger RNA; protein c fos; protein c jun; small interfering RNA; stromal cell derived factor 1; transcription factor AP 1; article; articular cartilage; bone destruction; cartilage cell; controlled study; drug effect; drug inhibition; enzyme phosphorylation; flow cytometry; human; human cell; immunoprecipitation; osteoarthritis; priority journal; protein expression; reverse transcription polymerase chain reaction; rheumatoid arthritis; synovial fluid; transcription regulation; Western blotting; zymography; Anti-HIV Agents; Arthritis, Rheumatoid; Cells, Cultured; Chemokines, CXC; Chondrocytes; Dose-Response Relationship, Drug; Heterocyclic Compounds; Humans; Matrix Metalloproteinase 13; Osteoarthritis; Receptors, CXCR4; RNA, Messenger; RNA, Small Interfering; Stromal Cells; Synovial Fluid; Synovial Membrane |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。