Selenium Attenuates Dexamethasone-Induced Osteoblast Dysfunction and Prevents Femoral Head Osteonecrosis via...

Glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) represents a devastating complication of steroid therapy, primarily driven by osteoblast apoptosis and impaired osteogenesis. Although selenium (Se) is renowned for its potent bone-protective properties, its therapeutic potential, and specific mechanisms in GC-ONFH remain largely unexplored and thus require further investigation.

To assess the therapeutic effectiveness of oral selenium supplementation in GC-ONFH, a rat model of GC-ONFH was utilized. The rats were randomly allocated into three groups (n = 6 per group): (1) Control group, (2) Methylprednisolone sodium succinate (MPS) group, and (3) Se group. The intervention was carried out for 4 weeks. In vitro experiments utilized primary rat osteoblasts and MC3T3-E1 cells to elucidate the mechanisms through which selenium mitigates dexamethasone (DEX)-induced alterations in cell proliferation, apoptosis, and osteogenic differentiation. The assessments were conducted using micro-CT and histomorphometry, CCK-8 assays and flow cytometry, as well as RT-qPCR, Western blotting, and immunofluorescence.

Selenium supplementation effectively prevented trabecular collapse and significantly reduced the number of empty lacunae in rats with GC-ONFH. Specifically, an optimal dose of 10 μmol Se successfully reversed the damage induced by DEX, including the restoration of cell proliferation, suppression of apoptosis, and rescue of osteogenic activity. Mechanistically, Se counteracts the DEX-induced suppression of phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-AKT), and phosphorylated glycogen synthase kinase 3β (GSK3β) (p-GSK3β), thereby activating the PI3K/AKT/GSK3β signaling pathway, which promotes cell proliferation, inhibits apoptosis, and enhances osteogenesis in osteoblasts.

Selenium can activate the PI3K/AKT/GSK3β pathway, reverse DEX-induced hypoproliferation and apoptosis, restore osteogenic capacity, prevent trabecular collapse, and attenuate GC-ONFH in rat models. Our findings demonstrate that selenium supplementation can be regarded as a clinically applicable strategy for impeding the progression of GC-ONFH in at-risk patients.