Erythropoietin suppresses osteoblast apoptosis and ameliorates steroid-induced necrosis of the femoral head in rats by inhibition of STAT1-caspase 3 signaling pathway.

Background: Steroid-induced avascular necrosis of the femoral head (SANFH) is characterized by osteoblast apoptosis, leading to a loss of bone structure and impaired hip joint function. It has been demonstrated that erythropoietin (EPO) performs a number of biological roles.

Objective: We examined the effects of EPO on SANFH and its regulation of the STAT1-caspase 3 signaling pathway.

Method: In vitro, osteoblasts were treated with dexamethasone (Dex) or EPO. We identified the cytotoxicity of EPO by CCK-8, the protein expression of P-STAT1, cleaved-caspase9, cleaved-caspase3, Bcl-2, BAX, and cytochrome c by Western blotting, and evaluated the apoptosis of osteoblasts by flow cytometry. In vivo, we analyzed the protective effect of EPO against SANFH by hematoxylin and eosin (H&E), Immunohistochemical staining, and Micro-computed tomography (CT).

Results: In vitro, EPO had no apparent toxic effect on osteoblasts. In Dex-stimulated cells, EPO therapy lowered the protein expression of BAX, cytochrome c, p-STAT1, cleaved-caspase9, and cleaved-caspase3 while increasing the expression of Bcl-2. EPO can alleviate the apoptosis induced by Dex. In vivo, EPO can lower the percentage of empty bone lacunae in SANFH rats.

Conclusion: The present study shows that EPO conferred beneficial effects in rats with SANFH by inhibiting STAT1-caspase 3 signaling, suggesting that EPO may be developed as a treatment for SANFH.