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摘要
Objective: Advanced glycation end products (AGEs) play a pivotal role in the initiation and progression of osteoarthritis (OA). Peroxisome proliferator-activated receptor-gamma (PPAR gamma) has been shown to exhibit anti-inflammatory and anticatabolic properties and to be protective in animal models of OA. This study was aimed to investigate the possible protective effect of the PPAR gamma agonist pioglitazone on AGE-induced chondrocyte damage. Methods: Cultured chondrocytes were stimulated with AGEs in the presence or absence of an antibody against the receptor for AGEs (anti-RAGE), an inhibitor of NF-kappa B (pyrrolidine dithiocarbamate) and pioglitazone. The RNA expression levels of TNF-alpha, matrix metalloproteinase (MMP)-13 and PPAR gamma were detected by RT-PCR. The expression of nuclear p65 was determined by Western blot analysis. Results: Upregulation of TNF-alpha and MMP-13 as well as downregulation of PPAR gamma were induced by AGEs in a time-and dose-dependent manner. The maximum effect was induced by 100 mu g/ml AGEs. This effect can be inhibited by anti-RAGE. Pioglitazone dose-dependently inhibited the expression of TNF-alpha and MMP-13 induced by AGEs, which was combined with the inhibition of nuclear p65 expression. Conclusion: The PPAR gamma agonist pioglitazone modulates TNF-alpha and MMP-13 expression in cultured rabbit chondrocytes via NF-kappa B signaling. It indicates that pioglitazone may have therapeutic potential in OA.
