Cross-Talk Between VEGF and BMP-6 Pathways Accelerates Osteogenic Differentiation of Human Adipose-Derived Stem Cells

Journal of Cellular Physiology
Ching-Ju LiQuanjun Cui

Abstract

Deficiency in vascular endothelial growth factor (VEGF) or bone morphogenetic proteins (BMPs) results in fracture non-unions. Therefore, it is indispensable to comprehend the combined effect of VEGF and BMPs on the osteogenic differentiation of osteoprogenitor mesenchymal stem cells (MSCs) that are either naturally occurring at the fracture repair site or exogenously added to enhance the bone repair. We found that the combination of VEGF and BMP-6 enhanced COL1A2 expression, which correlated with upregulated expression of osterix, Dlx5, and Msx2 in human adipose-derived stem cells (hADSCs). Cross-talk between VEGF and BMP-6 pathways upregulated activation of p38 mitogen-activated kinase (p38 MAPK) and inhibited activation of protein kinase B (PKB, also known as Akt), whereas phosphorylation of "mothers against decapentaplegic" homologs 1/5/8 (Smads 1/5/8) and extracellular signal-regulated kinases 1 and 2 (ERK 1/2) was not affected. Consistent with these findings, p38 inhibitor SB203580, or siRNA knockdown of osterix, abrogated crosstalk between the VEGF and BMP-6 pathways and significantly reduced the observed upregulation of COL1A2. Nuclear translocation of the phosphorylated form of osterix was also inhibited by SB203580. Al...Continue Reading

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