Stromal Cell-Derived Factor-1 Induces Matrix Metalloprotease-13 Expression in Human Chondrocytes
Resource
MOLECULAR PHARMACOLOGY v.72 n.3 pp.695-703
Journal
MOLECULAR PHARMACOLOGY
Journal Volume
v.72
Journal Issue
n.3
Pages
695-703
Date Issued
2007
Date
2007
Author(s)
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
Abstract
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.
Subjects
STIMULATES FIBRONECTIN EXPRESSION
SIGNAL-REGULATED KINASES-1/2
RHEUMATOID-ARTHRITIS
CHEMOKINE RECEPTOR-4
PHOSPHOLIPASE-C
CARCINOMA-CELLS