RESUMO
Aim To explore the mechanism of the protective effect of curcumin on advanced glycation end products (AGEs)-induced chondrocyte apoptosis and mitochondrial dysfunction whether by elevating peroxisome proliferators-activated receptor-γ (PPARγ) or not.Methods The ratio of apoptotic cells was assayed by TUNEL;the mitochondrial membrane potential(△Ψm) was evaluated by Rhodamine-123 fluorescence.The ATP content was assayed by related kits.The activity of caspase-3 was detected by spectrophotometry.The expression of cytochrome C,Bax,and Bcl-2 was detected by Western blot.The PPARγ expression was determined by Western blot and real-time PCR;in addition,its activity was assayed by DNA-binding method.Results AGEs could induce chondrocyte apoptosis and up-regulate the levels of cytochrome C and caspase-3.Simultaneously,AGEs decreased the levels of △ Ψm and ATP production.Mitochondrial permeability conversion pore inhibitor cyclosporine A could significantly protect the cells from apoptosis.In addition,both PPARγ specific agonist pioglitazone and curcumin significantly inhibited AGEs-induced chondrocytes apoptosis and mitochondrial dysfunction.However,pretreatment with PPARγ specific inhibitor GW9662 (10 μ mol · L-1) could significantly antagonize the protective effect of curcumin on mitochondrial damage induced by AGEs.Curcumin could also significantly increase PPARγtranscriptional activity induced by AGEs,together with a significant induction of PPARγprotein and mRNA expression.Conclusion Curcumin could effectively protect AGEs-induced chondrocyte mitochondrial dysfunction by upregulating PPARγ,thus protecting chondrocytes from apoptosis.