Advanced glycation end products increases matrix metalloproteinase‐1, ‐3, and ‐13, and TNF‐α in human osteoarthritic chondrocytes

Abstract

We investigated the effects of advanced glycation end products (AGE) which accumulate in articular cartilage with age in human osteoarthritic chondrocytes. We found AGE-BSA significantly increased MMP-1, -3, and -13, and TNF-alpha in a dose-dependent manner. AGE-BSA-stimulated JNK, p38, and ERK and NF-kappaB activity. The stimulatory effect of AGE-BSA on MMP-1, -3, and -13 were reversed by treatment with specific JNK, p38 inhibitors, suggesting JNK and p38 are involved in AGE-BSA-induced MMPs and TNF-alpha. We also observed that NF-kappaB is involved in AGE-BSA-induced TNF-alpha. Pretreatment with soluble receptor for AGE (sRAGE) also reduced AGE-stimulated MMPs and TNF-alpha, implicating the involvement of receptor for AGE (RAGE). In conclusion, accumulation of AGE may have a role in the development of osteoarthritis by increasing MMP-1, -3, and -13, and TNF-alpha.