Hypoxia Enhanced Bone Regeneration Through the HIF-1α/β-Catenin Pathway in Femoral Head Osteonecrosis

Background Osteonecrosis of the femoral head (ONFH) is a common disease. Transplantation of bone marrow stem cells (BMSCs) is a promising method to treat ONFH but is impeded by the low survival rate and deficiency of cell bioactivity. Methods We performed hypoxic preprocessing to treat BMSCs and assessed cell viability, apoptosis, differentiation, and growth factor expression in vitro. Subsequently, we constructed the ONFH model and delivered hypoxia-pretreated BMSCs to the rabbit femoral head after core decompression surgery, evaluating its effects on bone regeneration and ONFH repair. Six weeks later, micro-computed tomography (CT) and histopathology were performed to evaluate ONFH repair. Results Our findings demonstrated that hypoxic preprocessing promoted the viability of BMSCs, increased the expression of hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), alkaline phosphatase (ALP), calcium deposition, and enhanced the formation of vessels-shaped structures. In an in vivo study, micro-CT observations demonstrated that the bone volume was increased in the hypoxia BMSCs group. Histological examination revealed reduced cellular apoptosis, lower empty lacunae rate, enhanced bone formation, and stronger trabecular bone in the hypoxia BMSCs group when compared with those transplanted with normoxia treated BMSCs. Additionally, immunological assessment of the hypoxia BMSCs group demonstrated increased expression of HIF-1α and β-catenin, as well as increased VEGF, ALP, osteocalcin (OCN), and collagen type I (Col-1). Conclusions Collectively, our findings indicated that hypoxia stimulated angiogenesis and bone regeneration via the HIF-1/β-catenin pathway in BMSCs and that the delivery of hypoxia-pretreated BMSCs contributed to the treatment of early ONFH.