Dexamethasone induces ferroptosis in MC3T3-E1 cells by promoting DNMT3a-mediated Sirt1 DNA hypermethylation in the context of steroid-induced osteonecrosis of the femoral head

• Dexamethasone induces ferroptosis in MC3T3-E1 osteoblast cells via downregulation of Sirt1, a novel mechanism in steroid-induced osteonecrosis of the femoral head (SONFH). • Sirt1 overexpression rescues ferroptosis by upregulating SLC7A11 and GPX4, key ferroptosis suppressors, suggesting a potential therapeutic target. • Dexamethasone promotes DNMT3a-mediated hypermethylation of the Sirt1 promoter, linking epigenetic regulation to ferroptosis in SONFH. • This study provides new insights into the molecular pathogenesis of SONFH, offering potential biomarkers and targets for early diagnosis and therapy.