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DOI: 10.1055/s-2006-925177
Minodronate Suppresses Prostaglandin F2α-induced Vascular Endothelial Growth Factor Synthesis in Osteoblasts
Publication History
Received 12 July 2005
Accepted after revision 7 December 2005
Publication Date:
27 April 2006 (online)
![](https://www.thieme-connect.de/media/hmr/200603/lookinside/thumbnails/10.1055-s-2006-925177-1.jpg)
Abstract
In our previous study, we showed that prostaglandin F2α (PGF2α) stimulates vascular endothelial growth factor (VEGF) synthesis via activation of p44/p42 mitogen-activated protein (MAP) kinase via protein kinase C (PKC) in osteoblast-like MC3T3-E1 cells. In addition, we demonstrated that incadronate amplified, and tiludronate suppressed PGF2α-induced VEGF synthesis among bisphosphonates, while alendronate or etidronate had no effect. In the present study, we investigated the effects of minodronate, a newly developed bisphosphonate, on PGF2α-induced VEGF synthesis in MC3T3-E1 cells. Minodronate significantly reduced VEGF synthesis induced by PGF2α dose-dependently at levels between 3 and 100 µM. PGF2α-stimulated phosphorylation of Raf-1, MEK1/2 and p44/p42 MAP kinase were suppressed by minodronate. 12-O-tetradecanoylphorbol-13-acetate (TPA), a direct activator VEGF synthesis induced by PKC, was inhibited by minodronate. Minodronate inhibited Raf-1, MEK1/2 and p44/p42 MAP kinase phosphorylation induced by TPA. Mevalonate failed to affect the suppressive effect of minodronate on PGF2α-induced VEGF synthesis. Taken together, these results indicate that minodronate suppresses PGF2α-stimulated VEGF synthesis at the point between PKC and Raf-1 in osteoblasts.
Key Words
Bisphosphonate - prostaglandin F2α - vascular endothelial growth factor - osteoblast
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Osamu Kozawa
Department of Pharmacology · Gifu University Graduate School of Medicine
1-1 Yanagido · Gifu 501-1194 · Japan
Phone: +81 (58) 230-6214
Fax: +81 (58) 230-6215
Email: okozawa@cc.gifu-u.ac.jp