HIF-1α Transgenic Bone Marrow Cells Can Promote Tissue Repair in Cases of Corticosteroid-Induced Osteonecrosis of the Femoral Head in Rabbits

Abstract

Although corticosteroid-induced osteonecrosis of the femoral head (ONFH) is common, the treatment for it remains limited and largely ineffective. We examined whether implantation of hypoxia inducible factor-1α (HIF-1α) transgenic bone marrow cells (BMCs) can promote the repair of the necrotic area of corticosteroid-induced ONFH. In this study, we confirmed that HIF-1α gene transfection could enhance mRNA expression of osteogenic genes in BMCs in vitro. Alkaline phosphatase activity assay and alizarin red-S staining indicated HIF-1α transgenic BMCs had enhanced osteogenic differentiation capacity in vitro. Furthermore, enzyme linked immunosorbent assay (ELISA) for VEGF revealed HIF-1α transgenic BMCs secreted more VEGF as compared to normal BMCs. An experimental rabbit model of early-stage corticosteroid-induced ONFH was established and used for an evaluation of cytotherapy. Transplantation of HIF-1α transgenic BMCs dramatically improved the bone regeneration of the necrotic area of the femoral head. The number and volume of blood vessel were significantly increased in the necrotic area of the femoral head compared to the control groups. These results support HIF-1α transgenic BMCs have enhanced osteogenic and angiogenic activity in vitro and in vivo. Transplantation of HIF-1α transgenic BMCs can potentially promote the repair of the necrotic area of corticosteroid-induced ONFH.

Osteonecrosis of the femoral head: treatment with ancillary growth factors

“…It is known that hypoxia-inducible factor-1α (HIF-1α) is upregulated and increases the expression of other pro-angiogenic factors in the setting of ON, and as such, it is thought that the increased production of HIF-1α could lead to healing of the necrotic lesions [56,57]. In a rabbit model for ON, Ding and colleagues used a viral vector to increase the production of HIF-1α by bone marrow-derived MSCs implanted at the time of a core decompression [58]. The authors noted that through the increased production of HIF-1α, there was an increase in the expression of VEGF and increased osteogenesis [58].…”

“…In a rabbit model for ON, Ding and colleagues used a viral vector to increase the production of HIF-1α by bone marrow-derived MSCs implanted at the time of a core decompression [58]. The authors noted that through the increased production of HIF-1α, there was an increase in the expression of VEGF and increased osteogenesis [58]. This translated into the rabbit model, where the increased HIF-1α led to increased new blood vessel volume and bone formation in the necrotic lesion [58].…”

“…The authors noted that through the increased production of HIF-1α, there was an increase in the expression of VEGF and increased osteogenesis [58]. This translated into the rabbit model, where the increased HIF-1α led to increased new blood vessel volume and bone formation in the necrotic lesion [58].…”

Avascular necrosis of bone in childhood cancer patients: a possible role of genetic susceptibility

“…Ding et al in 2013 confi rmed the implementation of HIF-1α in activation of osteogenic genes expression and angiogenic activity by enhanced secretion of VEGF (66).…”

Biomarkers and pharmaceutical strategies in steroid-induced osteonecrosis of the femoral head: A literature review

“…Transplantation of hypoxia inducible factor (HIF)-1a transgenic bone marrow cells improved bone regeneration in necrotic regions of ONFH by enhancing mRNA expression of osteogenic genes and osteogenic differentiation. 43 …”