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Horm Metab Res 2009; 41(12): 861-865
DOI: 10.1055/s-0029-1233460
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Parathyroid Hormone Upregulates BMP-2 mRNA Expression Through Mevalonate Kinase and Rho Kinase Inhibition in Osteoblastic MC3T3-E1 Cells

H. Takase1 , S. Yano1 , T. Yamaguchi1 , I. Kanazawa1 , K. Hayashi1 , M. Yamamoto1 , M. Yamauchi1 , T. Sugimoto1
  • 1Shimane University Faculty of Medicine, Department of Internal Medicine 1, Enya-cho, Izumo, Japan
Further Information

Publication History

received 01.05.2009

accepted 17.06.2009

Publication Date:
11 August 2009 (online)

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Abstract

It is well known that parathyroid hormone (PTH) possesses an anabolic effect on bone. However, the mechanisms are not fully elucidated. So far, it is unclear whether or not PTH could stimulate the expression of bone morphogenetic protein-2 (BMP-2), a strong mediator for bone formation. Growing evidence suggests that BMP-2 expression is regulated by the mevalonate pathway and Rho-associated protein kinase (ROK) activity. This study was performed to examine if PTH affects BMP-2 expression and to clarify its involvement of the mevalonate pathway. Osteoblastic MC3T3-E1 cells were treated with human PTH-(1–34) to determine BMP-2 mRNA expression levels by real-time PCR and to measure the ROK activity by the kinase assay. Incubation with 10−9–10−8 M of hPTH-(1–34) for 6 h induced significant upregulation of BMP-2 mRNA levels in MC3T3-E1 cells. Short-term treatment of hPTH-(1–34) suppressed Rho kinase activity and mevalonate kinase mRNA levels. PTH-induced BMP-2 mRNA upregulation was selectively reversed by geranylgeranyl pyrophosphate (GGPP) pretreatment, but not by mevalonate pretreatment. These findings suggest that BMP-2 mRNA expression was upregulated by PTH in MC3T3-E1 cells mediated by mevalonate pathway suppression followed by ROK inhibition. We have now demonstrated for the first time that PTH stimulated BMP-2 mRNA expression via the mevalonate pathway and ROK in osteoblastic MC3T3-E1 cells.

Key words

osteoblast - parathyroid hormone - BMP-2 - Rho kinase

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Correspondence

S. Yano

Department of Internal Medicine 1

Shimane University Faculty of Medicine

89-1 Enya-cho

693-8501 Izumo

Japan

Phone: +81/853/20 21 83

Fax: +81/853/23 86 50

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

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