In vitro evaluation of rhBMP-2-induced expression of VEGF in human adipose-derived stromal cells.

Bone Morphogenetic Protein 2 (BMP-2) plays a key role in skeletal development, repair and regeneration. Our previous studies indicate that recombinant human BMP-2 (rhBMP-2) can stimulate osteogenic differentiation and promote angiogenesis through the up-regulation of Vascular Endothelial Growth Factor (VEGF), while the underlying mechanism of the BMP-2 effect on human cells is not well understood. To gain a better understanding of BMP-2-induced angiogenesis, we further characterized the effect of rhBMP-2 on VEGF expression in human adipose-derived stromal cells (hASCs) by RT-PCR and ELISA. VEGF expression was induced by rhBMP-2 in a dose- and time-dependent manner, with the highest induction observed using 100 ng/ml of rhBMP-2 at 18-24 h post stimulation. In addition, Western blot analyses revealed that the phosphorylation of p38 was closely related to the expression of VEGF, and blocking the p38MAPK pathway with the specific inhibitor sb203580 resulted in the decreased VEGF expression. Our data suggest that p38 activation may be required for rhBMP-2-induced VEGF expression and angiogenesis. Information derived from this study may shed light on understanding the effect of rhBMP-2 in the angiogenesis of hASCs, which is important for designing new strategies to increase the angiogenesis of tissue engineering bone.