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

Zhu, Zhen-Hong; Song, Wen-Qi; Zhang, Chang-Qing; Yin, Ji-Min

Corticosteroid-induced ONFH is a major type of ONFH, which is a serious complication of corticosteroid treatment for autoimmune diseases, such as systemic lupus erythematosus, nephrotic syndrome and rheumatoid arthritis (27) . The diagnostic or therapeutic strategy for ONFH is best introduced at the early stage before the disease becomes irreversible. Currently, the treatment methods of early-stage ONFH are highly controversial (28) . Core decompression is reported to be effective for early-stage ONFH, and acts to reverse the natural process of ONFH by providing a conduit for angiogenesis to revascularize subchondral bone and reducing elevated intraosseous pressures (29, 30) . However, the majority of studies about the effectiveness of core decompression suggest that the results of this approach are not satisfactory (31, 32) . The aseptic necrotic bone in the femoral head retains its normal strength until the natural process of revascularization starts to remove the dead bone in preparation for the formation of new bone. As repair advances, the speed of angiogenesis and osteogenesis becomes slower than absorption of the dead bone, which may cause a weakening of mechanical structure (3). Jones hypothesized that new capillaries could only penetrate 10-15 mm of necrotic bone, and subchondral bone tissue usually can not be repaired (33) . Furthermore, microfractures of the subchondral bone may retard capillary penetration, and then the loaded areas would collapse (33) . Thus, it is important for ONFH treatment to increase local vascularization and new bone formation. It has been reported that the MSCs pool of the femoral head could not provide enough osteoblasts to meet the need of local bone regeneration (34) . Researchers have also suggested that MSCs in the proximal femur have a decreased proliferative and differentiation capacity at the early stage of ONFH (35, 36) . Therefore, MSCs have been employed to aid core decompression to treat early-stage ONFH (11, 12, 37) . Hypoxia inducible factor-1a (HIF-1α) is an important functional subunit of the HIF family, which are crucial mediators of the adaptive cells response to hypoxia (17) . HIF-1α arose early in evolution, and is widely expressed in most human tissues (17) . A previous study found that HIF-1α controls the expression of numerous genes in cells, cell proliferation and differentiation (38) . Our previous study showed that, compared with normal MSCs, HIF-1α transgenic MSCs had improved osteogenic and angiogenic capacity in vitro and better potential to promote bone regeneration in the necrotic area of the femoral head (19) .