Selenomethionine against titanium particle-induced osteolysis by regulating the ROS-dependent NLRP3 inflammasome activation via the ß-catenin signaling pathway
Wear debris-induced osteolysis, especially titanium (Ti) particles-induced osteolysis, is the most common cause of arthroplasty failure with no effective therapy. Previous studies have suggested that inflammation and impaired osteogenesis are associated with Ti particles -induced osteolysis. Selenium (Se) is an essential trace element in the human body, which forms selenomethionine (Se-Met) in nature, and selenoproteins has strong anti-inflammatory and antioxidant stress effects. In this study, the effects of Se-Met on Ti particles-induced osteolysis were observed and the potential mechanism was explored. We found that exogenous Se-Met relieved osteolysis induced by Ti particles in two animal models and MC3T3-E1 cells. We found that the addition of Se-Met effectively inhibited Ti particle-induced inflammation by regulating ROS-dependent NLRP3 inflammasome activation. These therapeutic effects were abrogated in MC3T3-E1 cells that had received a ß-catenin antagonist, suggesting that Se-Met alleviates inflammatory osteolysis via the ß-catenin signaling pathway. Collectively, these findings indicated that Se-Met may serve as a potential therapeutic agent for treating Ti particle-induced osteolysis. Overall design: MC3T3-E1 cells were obtained from the Cell Bank of the Chinese Academy of Sciences (Shanghai, China). MC3T3-E1 cells were maintained in a-MEM (Gibco, Brooklyn, NY) containing 10% FBS, 100 µg/ml streptomycin, and 100 U/ml penicillin in a 5% CO2 humidified atmosphere at 37 °C, adherent cells were cultured until the cells reached approximately 90% confluence. The osteogenic medium was a-MEM supplemented with 10% FBS, 10 mM ß-glycerophosphate, 0.5 mM vitamin C, and 0.1 µM dexamethasone. The induction time of Osteogenesis was induced for 14 d. Osteolysis was induced by adding 10 µg/cm2 Ti particles. Cells were cultured in 6-well plates at a density of 1 × 105 cells/well in an incomplete medium and stimulated with 10 µg/cm2 Ti particles solution, with or without Se-Met (5 µM) for 24 h. The culture medium and cells were collected for further experiments