The Chondroprotective Role of TMF in PGE(2)-Induced Apoptosis Associating with Endoplasmic Reticulum Stress

Endoplasmic reticulum stress (ERS) has been demonstrated to exhibit a critical role in osteoarthritic chondrocytes. Whether 5,7,3′,4′-tetramethoxyflavone (TMF) plays the chondroprotective role in inhibition of PGE(2)-induced chondrocytes apoptosis associating with ERS has not been reported. To investigate this, the activation of PERK, ATF6, and IRE1 signaling pathways in ERS in chondrocytes pretreated with PGE(2) was studied. By treatment with PGE(2), the chondrocytes apoptosis was significantly increased, the proapoptotic CHOP and JNK were upregulated, the prosurvival GRP78 and XBP1 were downregulated, and GSK-3β was also upregulated. However, TMF exhibited the effectively protective functions via counteracting these detrimental effects of PGE(2). Finally, the inflammatory cytokine PGE(2) can activate ERS signaling and promote chondrocytes apoptosis, which might be associated with upregulation of GSK-3β. TMF exhibits a chondroprotective role in inhibiting PGE(2)-induced ERS and GSK-3β.