In the present study, we aimed to investigate three problems: (1) whether GC could induce mitochondrial-mediated apoptosis and inhibit angiogenesis of EPCs, (2) whether inhibition of PTEN with VO-OHpic could ameliorate the detrimental effects of GC via activating Nrf2 signaling pathway and inhibiting the mitochondrial apoptosis pathway, and (3) whether intraperitoneal injection of VO-OHpic could promote angiogenesis and inhibit osteonecrosis in GC associated ONFH in rats. Here, NFE2L2 is linked to osteonecrosis.