SYNERGISTIC INTERACTION BETWEEN VEGF AND BMP- 6 ENHANCES BONE FORMATION MEDIATED BY A CLONED MOUSE BONE MARROW STEM CELL

Introduction Enhanced angiogenesis and osteogenesis may provide new strategies for the treatment of osteonecrosis. Methods Synergistic effects of vascular endothelial growth factor (VEGF) and bone morphogenetic protein - 6 (BMP-6) on in vitro osteogenic differentiation and in vivo ectopic bone formation mediated by a cloned mouse bone marrow stromal cell line, D1, previously isolated from Balb/c mice in our laboratory, were determined. Results When human VEGF and BMP-6 genes both were expressed in D1 cells, significant increase in alkaline phosphatase activity was observed as compared to D1 cells in control groups. In the in vivo study, D1 cells transfected with hVEGF and hBMP-6 were loaded onto a 3-D PLAGA (polylactic-co-glycolic acid) scaffold and implanted subcutaneously in Balb/c mice. Micro-CT analysis of the retrieved implants clearly indicated the synergistic interaction of VEGF with BMP-6 as greater ectopic bone formation was observed in the VEGF plus BMP-6 group as compared to VEGF or BMP-6 alone. In addition, histology of the implants showed enhanced blood vessel formation with VEGF treatments. Conclusion This study demonstrated the synergistic interaction of VEGF with BMP-6 during osteogenesis in vitro and in vivo . The results indicated that this novel combination of therapeutic growth factors should be investigated further as a potential treatment of osteonecrosis.