Oxymatrine exerts protective effects on osteoarthritis via modulating chondrocyte homoeostasis and suppressing osteoclastogenesis

Osteoarthritis (OA) is a common degenerative disease characterized by the progressive destruction both articular cartilage and the subchondralbone. The agents that can effectively suppress chondrocyte degradation and subchondral bone loss are crucial for the prevention and treatment of OA. Oxymatrine (OMT) is a natural compound with anti-inflammatory and antitumour properties. We found that OMT exhibited a strong inhibitory effect on LPS-induced chondrocyte inflammation and catabolism. To further support our results, fresh human cartilage explants were treated with LPS to establish an exvivo degradation model, and the results revealed that OMT inhibited the catabolic events of LPS-stimulated human cartilage and substantially attenuated the degradation of articular cartilage exvivo. As subchondral bone remodelling is involved in OA progression, and osteoclasts are a unique cell type in bone resorption, we investigated the effects of OMT on osteoclastogenesis, and the results demonstrated that OMT suppresses RANKL-induced osteoclastogenesis by suppressing the RANKL-induced NFATc1 and c-fos signalling pathway invitro. Further, we found that the anti-inflammatory and anti-osteoclastic effects of oxymatrine are mediated via the inhibition of the NF-B and MAPK pathways. In animal studies, OMT suppressed the ACLT-inducedcartilage degradation, and TUNEL assays further confirmed the protective effect of OMT on chondrocyte apoptosis. MicroCT analysis revealed that OMT had an attenuating effect on ACLT-induced subchondral bone loss invivo. Taken together, these results show that OMT interferes with the vicious cycle associated with OA and may be a potential therapeutic agent for abnormalsubchondral bone loss and cartilage degradation in osteoarthritis.