Inhibition by minodronate of basic fibroblast growth factor-stimulated vascular endothelial growth factor synthesis in osteoblast-like cells.

In our previous study, we showed that basic fibroblast growth factor (bFGF) stimulates the synthesis of vascular endothelial growth factor (VEGF) via the activation of p44/p42 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of minodronate, a newly developed bisphosphonate, on bFGF-induced VEGF synthesis in MC3T3-E1 cells. Minodronate significantly reduced the synthesis of VEGF induced by bFGF in a dose-dependent manner in a range between 3 and 100 µM. The bFGF-stimulated phosphorylation of p44/p42 MAP kinase and SAPK/JNK was reduced by minodronate. These results strongly suggest that minodronate suppresses bFGF-stimulated VEGF synthesis via the inhibition of p44/p42 MAP kinase and SAPK/JNK in osteoblasts.