VEGF and BMP-6 enhance bone formation mediated by cloned mouse osteoprogenitor cells

Abstract

New strategies such as combined utilization of growth factors may provide a better treatment for difficult fractures. We have demonstrated enhanced angiogenesis and osteogenesis through the actions of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-6 (BMP-6) on the osteogenic differentiation of a cloned mouse osteoprogenitor cell in vitro and ectopic bone formation in vivo. Human VEGF and BMP-6 genes expressed together produced a significant increase in alkaline phosphatase activity, expression of the RunX2 and osteocalcin genes and mineralization. Microcomputed tomographic analysis of subcutaneous implants consisting of cells transfected with VEGF and BMP-6 cDNA and delivered on a 3D poly (lactic-co-glycolic acid) scaffold confirmed the additive effects between VEGF and BMP-6. Ectopic bone formation in the VEGF plus BMP-6 group was greatest compared to that in either VEGF or BMP-6 alone. This is the first study that demonstrates osteogenesis in vitro and in vivo through the additive effects of VEGF and BMP-6.

Keywords::

• Osteogenesis
• bone morphogenetic protein-6
• vascular endothelial growth factor
• angiogenesis

Acknowledgments

The authors wish to thank Dr Gerald Hankins for his kind gift of Human VEGF plasmid.

Declaration of interest: This study was partly supported by a grant from Orthopaedic Research and Education Foundation (OREF) and a grant from Synthes. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.