Phosphoproteome and proteome analysis of mice primary osteoblasts and osteoclasts after high iron treatment

Osteoporosis (OP) is a systemic bone disease characterized by low bone mass, damaged bone microarchitecture, increased fragility, and susceptibility to fractures. Osteoporotic fractures are one of the main causes of death and disability in elderly patients. Ferroptosis is a novel form of programmed cell death caused by uncontrolled iron-dependent lipid peroxidation. In this study, we found that high-iron intervention induced ferroptosis in osteoblasts through in vivo and in vitro experiments. Ferroptotic osteoblasts secrete factors such as RANKL to promote osteoclast differentiation, resulting in an osteoporotic phenotype in mice. We believe that high-iron intervention in mice can serve as a new model simulating clinical osteoporosis, and targeting ferroptosis in osteoblasts may become a potential therapeutic target for osteoporosis. In a word, our research provides new insights into the pathogenesis of OP and offers new potential therapeutic targets for treatment of clinical OP.