• Dexamethasone induces ferroptosis in osteoblasts by downregulating SLC7A11 and GPX4, leading to lipid peroxidation and cell death.
• lncRNA XR_877193.1 is significantly upregulated in Dex-treated MC3T3-E1 cells, and its knockdown suppresses ferroptosis and promotes osteogenic differentiation.
• The protective effect of lncRNA XR_877193.1 knockdown is mediated via activation of the PI3K/AKT signaling pathway.
• Targeting lncRNA XR_877193.1 may offer a novel therapeutic strategy for treating steroid-induced osteonecrosis of the femoral head.