TMF protects chondrocytes from ER stress-induced apoptosis by down-regulating GSK-3β.

Endoplasmic reticulum (ER) stress-induced chondrocyte apoptosis plays a critical role in osteoarthritis cartilage degeneration. Previous studies showed that 5,7,3',4'-tetramethoxyflavone (TMF) exhibited chondroprotective activity through inhibiting PGE2-induced ER stress and down regulating the expression of GSK-3β. To further investigate the role of GSK-3β in ER stress-induced chondrocytes apoptosis and the protective role of TMF, GSK-3β siRNA and pcDNA3.1-myc-GSK-3β were employed to knock down and overexpress GSK-3β, respectively, in chondrocytes. Results showed that TM-induced ER stress significantly promoted chondrocytes apoptosis. These could be effectively reversed by GSK-3β deficiency, while GSK-3β overexpression significantly up regulated ER stress and increased chondrocytes apoptosis. In addition, TMF down regulated the expression of GSK-3β and inhibited ER stress-induced chondrocytes apoptosis. Collectively, TMF is a potential natural compound with chondroprotective property through inhibition of ER stress-induced apoptosis with down regulation of GSK-3β.