Oxypaeoniflorin Ameliorates Titanium Particle‐Stimulated Osteolysis by Targeting Nrf2 to Reprogram Mitochondrial Homeostasis in Osteoclasts

Wear debris surrounding implants plays a crucial role in the development of periprosthetic osteolysis (PPO) by inducing the aggregation of osteoclasts around the prosthesis. Oxypaeoniflorin (OPF), a derivative of Paeoniflorin, is primarily sourced from the root of the traditional Chinese medicine peony and possesses anti-inflammatory and antioxidant properties. Currently, the effects of OPF on osteoclast activation and particle-induced bone resorption remain unclear. In this study, we examined the regulatory effect of OPF on titanium particle-induced bone erosion in vivo and utilized bone marrow macrophages to investigate the impact of OPF on osteoclast differentiation and resorptive function along with its potential mechanisms. Our results indicate that in vitro, OPF inhibits RANKL-induced osteoclastogenesis, osteoclast-dependent resorption, and the expression of osteoclast marker genes through the activation of Nrf2-mediated oxidative stress signalling. Furthermore, in vivo, OPF suppressed titanium particle-induced bone loss and osteoclast formation. Our data further confirm the protective effect of OPF against titanium particle-induced osteolysis from a novel perspective of preventing bone erosion, establishing OPF as a suitable drug for the prevention of PPO.