To investigate the protective effects of Selenomethionine （Se） against Dexamethasone （DEX）-induced apoptosis and osteogenic inhibition in osteoblasts （OB），and evaluate its protective role in steroid-induced osteonecrosis of femoral head （SONFH） in rats.

MC3T3-E1 cells were cultured in vitro and divided into 3 groups： control group （no intervention），DEX group （10 μmol/L DEX），and DEX+Se group （DEX 10 μmol/L + Se 10 μmol/L）. Cell proliferation was assessed using the CCK-8 assay. Osteogenic differentiation was evaluated via Real-time PCR and Western blot analysis. Intracellular reactive oxygen species （ROS） accumulation was measured using the 2'，7'-dichlorofluorescein diacetate （DCFH-DA） probe. Apoptosis was analyzed by flow cytometry，Real-time PCR，and Western blot. The effects of Se on the PI3K/Akt/GSK-3β signaling pathway under DEX exposure were examined using Western blot. Tweleve eight-week-old male SD rats were divided into 3 groups with 4 rats in each group. They were divided into normal saline control group, methylprednisolone (MPS) model group and MPS+Se intervention group respectively for intervention after all received intramuscular injection of lipopolysaccharide. Histological evaluation via hematoxylin-eosin （HE） staining was performed to assess the occurrence and treatment of empty bone lacunae.

Treatment with DEX increased ROS production，enhanced apoptosis levels and significantly suppressed osteogenic differentiation capacity in MC3T3-E1 cells. However, Se could inhibit cell apoptosis by reducing the accumulation of ROS in DEX-mediated OB potentially through activation of the PI3K/Akt/GSK-3β signaling pathway and also effectively alleviated DEX-mediated ostengenic dysfunction. In rats administered Selenium by gavage, the arrangement and quantity of trabecular bone were significantly improved compared with those in the MPS model group, the number of empty bone lacunae was reduced, and manifestation of osteonecrosis was between that of control group and MPS model group.

Selenomethionine may protect against SONFH by activating the PI3K/Akt/GSK-3β signaling pathway，thereby reversing DEX-induced osteogenic inhibition，oxidative stress damage，and apoptosis in osteoblasts. Se could serve as a potential therapeutic agent for the prevention and treatment of SONFH.