骨科CHIU, YUNG-CHENGYUNG-CHENGCHIUYANG, RONG-SENRONG-SENYANGHSIEH, KUO-HSIENKUO-HSIENHSIEHFONG, YI-CHINYI-CHINFONGWAY, TZONG-DERTZONG-DERWAYLEE, TU-SHENGTU-SHENGLEEWU, HSI-CHINHSI-CHINWUFU, WEN-MEIWEN-MEIFUTANG, CHIH-HSINCHIH-HSINTANG2008-12-222018-07-132008-12-222018-07-132007http://ntur.lib.ntu.edu.tw//handle/246246/92434ABSTRACT 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.en-USSTIMULATES FIBRONECTIN EXPRESSIONSIGNAL-REGULATED KINASES-1/2RHEUMATOID-ARTHRITISCHEMOKINE RECEPTOR-4PHOSPHOLIPASE-CCARCINOMA-CELLS