Abstract:Objective: To investigate the role of Netrin-1-enhanced bone marrow mesenchymal stem cells (BMSC) on the treatment of osteoporotic fracture and its mechanism. Methods: The apoptotic level of BMSC and the expression of human leukocyte antigen-G (HLA-G) were detected by flow cytometry. Mice models with osteoporotic fracture were built. Concentrations of alkaline phosphatase, tartrate resistant acid phosphatase (TRAP) and osteocalcin were detected by ELISA, and the number of human BMSC and macrophages in bone tissue was detected by immunohistochemistry. Results: Flow cytometry showed that Netrin-1 was able to inhibit the apoptosis of BMSC induced by ischemia and hypoxia (F=27.311, P=0.000), and increase the expression of HLA-G (F=27.094, P=0.000). BMSC was able to reduce the concentration of alkaline phosphatase and TRAP in serum, and increase the concentration of osteocalcin in serum, the number of osteocytes in bone tissue and the bone mineral density. Netrin-1 was able to further enhance functions of BMSC. Compared with the BMSC group, the difference was statistically significant. Immunohistochemical results showed that the number of surviving BMSCs in the BMSC group was (10.401±1.392) /high-power field (HPF) and was (25.506±2.257) /HPF in the Netrin-1 group, with significant differences between two groups (t=5.694, P=0.000). The number of macrophages in the BMSC group was (21.900±4.458) /HPF, which was significantly different from that in the osteoporosis group. The number of macrophages in the Netrin-1 group was (11.500±3.808) /HPF, which was significantly different from that in the BMSC group (F=79.863, P=0.000). Conclusion: Netrin-1 can enhance the therapeutic effect of BMSC on osteoporotic fracture through cell protection and regulation of inflammatory reaction.
