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Horm Metab Res 2009; 41(8): 612-616
DOI: 10.1055/s-0029-1220684
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Inhibition of the Mevalonate Pathway Rescues the Dexamethasone-induced Suppression of the Mineralization in Osteoblasts via Enhancing Bone Morphogenetic Protein-2 Signal

I. Kanazawa 1 , T. Yamaguchi 1 , S. Yano 1 , K. Hayashi 1 , M. Yamauchi 1 , T. Sugimoto 1
  • 1Department of Internal Medicine 1, Shimane University Faculty of Medicine, lzumo Japan
Further Information

Publication History

received 15.01.2009

accepted 25.03.2009

Publication Date:
21 April 2009 (online)

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Abstract

We used dexamethasone (DEX)-treated osteoblastic MC3T3-E1 cells, and investigated the effects of an AMP-activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleoside (AICAR), a Rho-associated protein kinase inhibitor, fasudil hydrochrolide, as well as HMG-CoA reductase inhibitors, simvastatin and pitavastatin, all of which inhibit the mevalonate pathway. DEX (10−8 M) significantly enhanced mRNA expression of bone morphogenetic protein (BMP)-2 antagonists, follistatin and Dan, and addition of each of 10−4 M AICAR, 10−5 M fasudil, 10−6 M simvastatin, and 10−6 M pitavastatin significantly reversed the enhancement in mRNA expression of follistatin and Dan and stimulated that of BMP-2 in the cells (p<0.05). DEX (10−8 M) also significantly suppressed mineralization in the cells, and addition of each of these agents significantly reversed the suppression of mineralization (p<0.05). These findings suggest that the mevalonate pathway was involved in glucocorticoid-induced osteoblast dysfunction, and that its inhibition might promote bone formation through BMP-2 and alleviate glucocorticoid-induced osteoporosis.

Key words

glucocorticoid - osteoblast - BMP-2 - mevalonate pathway

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Correspondence

T. Yamaguchi

Department of Internal Medicine 1

Shimane University Faculty of Medicine

89-1 Enya-cho

Izumo 693-8501

Japan

Phone: +81/853/20 21 83

Fax: +81/853/23 86 50

Email: yamaguch@med.shimane-u.ac.jp

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