Horm Metab Res 2006; 38(3): 152-158
DOI: 10.1055/s-2006-925177
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Minodronate Suppresses Prostaglandin F2α-induced Vascular Endothelial Growth Factor Synthesis in Osteoblasts

Y.  Hanai1, 2 , H.  Tokuda1, 2 , S.  Takai1 , A.  Harada3 , T.  Ohta4 , O.  Kozawa1
  • 1Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan
  • 2Department of Clinical Laboratory, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Aichi, Japan
  • 3Functional Restoration, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Aichi, Japan
  • 4Internal Medicine, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Aichi, Japan
Further Information

Publication History

Received 12 July 2005

Accepted after revision 7 December 2005

Publication Date:
27 April 2006 (online)

Abstract

In our previous study, we showed that prostaglandin F (PGF) 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 PGF-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 PGF-induced VEGF synthesis in MC3T3-E1 cells. Minodronate significantly reduced VEGF synthesis induced by PGF dose-dependently at levels between 3 and 100 µM. PGF-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 PGF-induced VEGF synthesis. Taken together, these results indicate that minodronate suppresses PGF-stimulated VEGF synthesis at the point between PKC and Raf-1 in osteoblasts.

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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