rhBMP-2 regulates vascular endothelial growth factor expression in human adipose mesenchymal stem cells via p38 pathway

Objective To study the role of p38 pathway in the regulation of vascular endothelial growth factor (VEGF) expression by recombinant human bone morphogenetic protein-2 (rhBMP-2) in human adipose-derived stem cells (hADSCs).Methods hADSCs were isolated from adult human adipose tissue and cultured until passage 3.Then the cells were induced with rhBMP-2 at final concentrations of 0 ng/mL,50 ng/mL,100 ng/mL and 200 ng/mL respectively.Samples were collected after incubation for 24 hours.Before using 100 ng/mL rhBMP-2,the cells were first inhibited by p38 inhibitor sb203580 at concentrations of 0 μmol/mL,5 μ mol/mL and 15 μmol/mL for 30 minutes.Samples were collected after incubation for 24 hours.RT-PCR and Western-blot were used to detect the changes in expressions of VEGF and p38 and their relevance was compared.Results The expression of VEGF was closely related to the phosphorylation of p38.In 0 ng /mL group,the expression of VEGF and activation level of p-p38 were low.In 100 ng/mL group,the expression of VEGF and the activation level of p-p38 were significantly higher than in other groups (P ＜ O.05).In 200 ng/mL group,rhBMP-2 inhibited the VEGF expression and the activation level of p-p38 was also inhibited.p38 inhibitor sb203580 inhibited the VEGF expression in a concentration dependent manner,with the VEGF barely expressed in 15 μmol/mL group.Conclusion p38 signaling pathways is involved in the regulation of VEGF expression by rhBMP-2 in hADSCs. Key words: Bone morphogenetic proteins;  Vascular endothelial growth factor;  Mesenchymal stem cells