Morroniside alleviates CoCrMo particle-induced osteogenic impairment by activating Wnt/β-catenin signalling

Periprosthetic osteolysis (PPO) is the main cause of aseptic loosening after total joint arthroplasty, often resulting from wear particle-induced osteogenic impairment. Morroniside (Mor), a major bioactive iridoid glycoside from C. officinalis, has been shown to have protective effects in osteoporosis. However, its efficacy against wear particle-induced osteolysis remains elusive. Herein, we evaluated the anti-PPO efficacy of Mor using a CoCrMo particle (CoP)-induced murine calvarial osteolysis model, and investigated the protective effects and signalling pathways associated with osteogenesis in CoP-stimulated mice and MC3T3-E1 cells. The results demonstrated that Mor effectively attenuated CoP-induced osteolysis in mice. Additionally, it reversed osteogenic impairment in both CoP-stimulated mice and MC3T3-E1 cells. Mechanistically, this protection was mediated by activating the Wnt/β-catenin signalling pathway in both in vivo and in vitro models. Notably, inhibiting the Wnt signalling pathway with XAV939 abolished the protective effects of Mor in both models. These findings indicate that Mor alleviates CoP-induced osteolysis by restoring osteogenic function via the Wnt/β-catenin pathway, highlighting its potential as a therapeutic agent for PPO.