5,7,3',4'-Tetramethoxyflavone exhibits chondroprotective activity by targeting β-catenin signaling in vivo and in vitro.

Osteoarthritis (OA) is a progressive joint disorder, which remains the leading cause of chronic disability in aged people. This study is the first report which demonstrates the cartilage protective effect of 5,7,3',4'-tetramethoxyflavone (TMF) by decreasing the concentration of IL-1β, TNF-α and PGE2 in the knee synovial fluid in OA rat models in vivo. In vitro, after induced by PGE2, the apoptosis rate of chondrocytes was significantly increased. In addition, PGE2 increased the expression of cAMP/PKA signaling pathway in chondrocytes, stabilized and accumulated β-catenin, and activated the expression of β-catenin signaling pathway. These activities were counteracted by TMF dose-dependently. Collectively, TMF is a potential compound with chondroprotective activity by inhibiting both EP/cAMP/PKA signaling pathway and β-catenin signaling pathway.