Phellopterin Inhibits Inflammation and Relieves Cartilage Degradation by Suppressing MAPK Signaling in Osteoarthritis

Osteoarthritis (OA) is thought to be the most common joint disorder and a major cause of disability and socioeconomic burden worldwide. Phellopterin has been demonstrated to exert anti-inflammatory effects in various diseases. However, the function of phellopterin in OA remains unclear. In this study, we aimed to investigate the role and mechanism of action of phellopterin in OA. We found that phellopterin promoted the proliferative ability and repressed the apoptotic ability of interleukin-1β (IL-1β)-treated ATDC5 cells. Our data also confirmed that phellopterin relieved inflammatory mediators release and extracellular matrix (ECM) degradation in vitro. In vivo, phellopterin significantly attenuated cartilage degradation and inflammation in OA rats. Moreover, we demonstrated that phellopterin could inhibit the activation of mitogen-activated protein kinase (MAPK) signaling pathway in both IL-1β-induced ATDC5 cells and OA rats. Rescue experiment results revealed that overexpression of extracellular signal-regulated kinase, c-Jun N-terminal kinase, or p38 MAPK reversed the influences of phellopterin on the proliferation, apoptosis, inflammatory mediators release, and ECM degradation in IL-1β-treated ATDC5 cells. Collectively, these findings demonstrated that phellopterin could inhibit inflammatory response and ameliorate cartilage degradation by suppressing MAPK signaling pathway in OA.