EPO could be regulated by HIF-1 and promote osteogenesis and accelerate bone repair

Abstract

Bone defects caused by many factors prompt further study of pathological process and restoration methods. This study was aimed to clarify the effect of erythropoietin on the repair of bone defect. We added the designated concentration of rhEPO to endothelial progenitor cells and marrow stromal cells, then detected its osteogenic and angiogenesis effects. The results showed that rhEPO promoted the proliferation of EPC and ST2 by promoting the mitosis without affecting cell apoptosis. The protein and mRNA levels of angiogenesis and osteogenic related factors exhibited higher expressions. Additionally, rhEPO encapsulated in PLGA scaffolds accelerated the new bone formation in rat calvaria bone defect model. Since the centre of bone defect was hypoxia environment, we cultured EPC and ST2 under hypoxia. SiRNA and an inhibitor of HIF-1 were used to interfere HIF-1, then the following changes of VEGF and EPO were detected. The results showed that all the factors were upregulated under the hypoxia environment. The expression of VEGF at protein and mRNA level decreased as HIF-1 was inhibited or interfered from 6 h, while the mRNA expression of EPO from 6 h and changed significantly at protein level from 12 h. Therefore, EPO is a promising factor for further studies.

Keywords

• Hypoxia-inducible factor
• erythropoietin
• bone defects
• angiogenesis
• osteogenesis