VEGF and BMP-6 enhance bone formation mediated by cloned mouse osteoprogenitor cells.
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.
Cui
Fuai
F
Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong, 250012, PR China. cuifuai@sdu.edu.cn
Wang
Xiuli
X
Liu
Xianxi
X
Dighe
Abhijit S
AS
Balian
Gary
G
Cui
Quanjun
Q
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055418:Bone Morphogenetic Protein 6 / Q000235:genetics*; D001861:Bone Regeneration; D002113:Calcification, Physiologic; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D015675:Osteocalcin / Q000032:analysis; D010012:Osteogenesis; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D055418:Bone Morphogenetic Protein 6; D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; D042461:Vascular Endothelial Growth Factor A; D015675:Osteocalcin; D000469:Alkaline Phosphatase