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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Cell Survival / drug effects
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Chondrocytes / drug effects*
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Chondrocytes / metabolism
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Chondrocytes / pathology
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Glycation End Products, Advanced / pharmacology*
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Humans
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Matrix Metalloproteinase 1 / metabolism*
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Matrix Metalloproteinase 13 / metabolism*
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Matrix Metalloproteinase 3 / metabolism*
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Middle Aged
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Osteoarthritis / metabolism*
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Osteoarthritis / pathology
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Phenotype
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Receptor for Advanced Glycation End Products
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Receptors, Immunologic / metabolism
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Receptors, Immunologic / physiology
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Signal Transduction / drug effects
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Tumor Necrosis Factor-alpha / metabolism*
Substances
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Glycation End Products, Advanced
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Receptor for Advanced Glycation End Products
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Receptors, Immunologic
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Tumor Necrosis Factor-alpha
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MMP13 protein, human
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Matrix Metalloproteinase 13
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MMP3 protein, human
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Matrix Metalloproteinase 3
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Matrix Metalloproteinase 1