Effects of Different Ratios of BMP2 and VEGFA on the Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells

Abstract Bone morphogenetic protein-2 (BMP2) and vascular endothelial growth factor (VEGF) have been shown to synergistically promote bone formation via cell-based gene therapy. However, the optimal ratio of BMP2 to VEGFA required to enhance the beneficial effect on bone formation remains unclear. In the present study, bone narrow-derived mesenchymal stem cells (BMSCs) were adenovirally transduced to express BMP2 and VEGFA. Cell proliferation and the expressions of transduced genes BMP2 and VEGF were examined.The different proportion of BMP2 and VEGF (BMP-2:VEGFA = 1:3, 1:1, 3:1; BMP2 only; VEGFA only; control) in BMSCs were applied. After 2–3 weeks, Osteocalcin (OC) and Runt-related transcription factor 2 (Runx2), ALP activity, and ARS staining were detected. Our results showed that the high ratio of BMP2 to VEGFA enhanced bone formation and the low ratio lost the beneficial effect on the bone formation. The present study revealed that the synergistic effect of BMP2 and VEGFA on bone healing depends critically on the ratio of these two genes, providing important evidence for cell-based gene therapy and tissue engineering for bone healing.