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.

Gene Therapy Applications for Fracture Repair

“…Likewise, combination therapy of BMP-2 and BMP-7 transduction of cells implanted into a cranial defect enhanced healing (Koh et al, 2008). Combination therapy of VEGF and BMP-6 transduction of osteoprogenitor cells has also shown preliminary promising results for future fracture repair studies (Cui et al, 2010). In addition to BMPs, one study found that cells transduced with IGF-I injected post-fracture resulted in accelerated progression toward complete fracture healing as measured by percent of mineralized callus and mineralized matrix compared to controls (Shen et al, 2002).…”

Interactions between osteopontin and vascular endothelial growth factor: Implications for skeletal disorders

“…Physical scaffold parameters, such [2] and proliferation of pre-osteoblastic cells [3] A late-stage osteogenic differentiation marker, induced by Wnt/β-catenin signaling […”

“…Throughout the processes of osteoblast differentiation, matrix mineralization, tissue repair and bone regeneration, the expression and levels of OPN and VEGF vary (Table 1) [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16].…”

Emerging Ideas: Treatment of Precollapse Osteonecrosis Using Stem Cells and Growth Factors

“…Combined use of VEGF and BMP-2 [19,24,34,35,37,40] and BMP-4 [20,25,36] showed synergistic effects in osteogenesis. It has been shown that combined use of VEGF with one of the most potent BMPs, BMP-6 [23,26], enhances osteogenesis and angiogenesis of mouse bone marrow stem cells in vitro and in vivo [8], however, the effectiveness of this therapy for ON has not been determined.…”

“…It has been shown that VEGF enhances BMP-6-induced osteogenesis of mouse stem cells in vitro and in vivo, however, the effectiveness of this therapy for ON has not been determined [8]. If it is effective in treating ON induced in an animal model, then the composite graft material can be used to treat the human form of the disease.…”