Potentiation by platelet-derived growth factor-BB of FGF-2-stimulated VEGF release in osteoblasts

We previously reported that basic fibroblast growth factor (FGF-2) stimulates the release of vascular endothelial growth factor (VEGF) via p44/p42 mitogenactivated protein (MAP) kinase and stress-activated protein kinase/c- Jun N-terminal kinase (SAPK/JNK) in osteoblastlike MC3T3-E1 cells. In the present study, we investigated the effect of platelet-derived growth factor-BB (PDGF-BB) on FGF-2-induced VEGF release in MC3T3-E1 cells. PDGF-BB significantly enhanced the FGF-2-stimulated VEGF release. The amplifying effect of PDGF-BB was dose dependent in the range between 0.1 and 30 ng/ml. AG1295, a selective inhibitor of PDGF receptor kinase, which reduced the autophosphorylation of PDGF receptor-®, suppressed the enhancement by PDGF-BB without affecting the FGF-2 effect. PDGF-BB failed to strengthen the FGF-2-induced phosphorylation of p44/p42 MAP kinase or SAPK/JNK. The amplification by PDGF-BB of FGF-2-stimulated VEGF release was reduced by PD98059, a specific inhibitor of MEK, or SP600125, a specific inhibitor of SAPK/JNK. These results strongly suggest that PDGF-BB potentiates FGF-2-stimulated VEGF release at a point downstream from p44/p42 MAP kinase and SAPK/JNK in osteoblasts.