Dimethyloxaloylglycine increases bone repair capacity of adipose-derived stem cells in the treatment of osteonecrosis of the femoral head.

Abstract

Mesenchymal stem cells have been widely studied to promote local bone regeneration of osteonecrosis of the femoral head (ONFH). Previous studies observed that dimethyloxaloylglycine (DMOG) enhanced the angiogenic and osteogenic activity of mesenchymal stem cells by activating the expression of hypoxia inducible factor-1α (HIF-1α), thereby improving the bone repair capacity of mesenchymal stem cells. In the present study, it was investigated whether DMOG could increase the bone repair capacity of adipose-derived stem cells (ASCs) in the treatment of ONFH. Western blot analysis was performed to detect HIF-1α protein expression in ASCs treated with different concentrations of DMOG. The results showed DMOG enhanced HIF-1α expression in ASCs in a dose-dependent manner at least for 7 days. Furthermore, DMOG-treated ASCs were transplanted into the necrotic area of a rabbit model of ONFH to treat the disease. Four weeks later, micro-computed tomography (CT) quantitative analysis showed that 58.8±7.4% of the necrotic area was regenerated in the DMOG-treated ASCs transplantation group, 45.5±3.4% in normal ASCs transplantation group, 25.2±2.8% in only core decompression group and 10.6±2.6% in the untreated group. Histological analysis showed that transplantation of DMOG-treated ASCs clearly improved the bone regeneration of the necrotic area compared with the other three groups. Micro-CT and immunohistochemical analysis demonstrated the revasculation of the necrotic area were also increased significantly in the DMOG-treated ASC group compared with the control groups. Thus, it is hypothesized that DMOG could increase the bone repair capacity of ASCs through enhancing HIF-1α expression in the treatment of ONFH.