Advanced Glycation End Products Increase Matrix Metalloproteinases in Human Osteoarthritic Chondrocytes / 대한류마티스학회지

ABSTRACT

OBJECTIVE: Although increased expression of receptor for advanced glycation end products (AGE) in osteoarthritis (OA) has been reported, little is known concerning the role of AGEs in the pathogenesis of OA. This study was undertaken to determine the effect of AGEs on the regulation of matrix metalloproteinase (MMP) expressions and activities in human OA chondrocytes METHODS: OA chondrocytes were treated with increasing doses of AGE-bovine serum albumin (AGE-BSA). The expressions of MMPs were determined by both enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis. The activities of MMPs were evaluated by both gelatin and casein zymography assays. In addition, electrophoretic mobility shift assay (EMSA) was employed to investigate the DNA binding activity of nuclear factor-kappa B (NF-kappaB) by AGE-BSA treatment. RESULTS: The productions of MMP-1, -3, and -13 were significantly elevated by AGE-BSA in a dose dependent manner. The elevated activities of MMP-1, -3, and -13, and TNF-alpha by AGE-BSA were also observed. DNA binding activity of NF-kappaB was markedly increased by AGE-BSA treatment implicating possible involvement of NF-kappaB mediated pathway in the AGE-BSA induced MMP-1, -3, and -13, and TNF-alpha productions in OA chondrocytes. Taken together, this study demonstrates the stimulatory effect of AGE-BSA on the productions of MMPs and TNF-alpha and suggests the possible involvement of NF-kappaB mediated pathway in OA chondrocytes. CONCLUSION: These results suggest that AGE may play a role in pathogenesis of OA.