SDF-1/CXCR4 AXIS REGULATE BOTH VASCULOGENESIS AND OSTEOGENESIS FOR BONE FRACTURE HEALING

Introduction CXC chemokine receptor 4 (CXCR4) is a specific receptor for stromal-derived-factor 1 (SDF-1). SDF-1/CXCR4 interaction contributes to the regulation of endotherial progenitor cell (EPC) recruitment in ischemic tissues. The purpose of this study is to investigate the mechanistic function of CXCR4 on EPCs for bone fracture healing. Materials and methods We made CXCR4 gene knockout mice using the Cre/loxP system. A reproducible model of femoral fracture was created in both Tie2-Cre CXCR4 knockout mice (CXCR4KO) and wild type mice (control). To evaluate gain function of the SDF-1/CXCR4 pathway, we set three groups of the SDF-1 intraperitoneally injected group, wild type group, and SDF-1 injected CXCR4 KO group. Results In morphological examinations, relative callus area at week 2 was significantly greater in control group. Real time RT-PCR analysis showed that the gene expressions of angiogenic and osteogenic markers were higher in wild type group. CXCR4KO group represented a significantly lower perfusion value at fracture site than control group. In gain function study, the fracture in the SDF-1 injected group is significantly faster healed. Conclusion Our results indicated the significance of SDF-1/CXCR4 signal in EPCs to bone fracture healing. This study also suggested that the promotion of CXCR4/SDF-1 signal on EPCs lead to the acceleration of bone fracture healing for new therapeutic strategies to fracture repair.