TMF通过调控Sirt1/STAT3信号通路抑制骨关节炎软骨胞外基质降解OA

Objective:Osteoarthritis(OA)is a degenerative joint disease characterized by extracellular matrix(ECM)degradation,chondrocyte apoptosis,and chronic inflammation.Cartilage destruction and ECM degeneration contribute to joint function loss and disability.Signal transducer and activator of transcription 3(STAT3)up-regulates the expression of MMP-13,which degrades collagen Ⅱ.Our previous study found that 5,7,3',4'-tetramethoxyflavone(TMF)exhibited protective effects on OA chondrocytes.This study aims to investigate the protective role of TMF in inhibiting ECM degradation by mediating the Sirt1/STAT3 signaling pathway.Methods:Rat OA models were established by the injection of monosodium iodoacetate(MIA).Hematoxylin&eosin(HE)staining and immunohistochemistry(IHC)analysis were performed.IL-1β stimulated C28/I2 cells were used as OA-like chondrocyte cell model.Western blotting assays were used to determine the protein expression.Results:The expression of MMP-13 was upregulated while type Ⅱ collagen expression is downregulated,and the phosphorylation level of STAT3 is increased in rat OA models.TMF reverses the STAT3-mediated expression of MMP-13 and type v collagen.Activation of STAT3 or inhibition of Sirt1 function attenuates the inhibitory effect of TMF on ECM degradation.Conclusion:TMF can inhibit ECM degradation mediated by the STAT3 signal pathway by activating Sirt1 expression in OA cell and animal models.