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Genistein modulates the effects of parathyroid hormone in human osteoblastic SaOS-2 cells

Published online by Cambridge University Press:  08 March 2007

Wen-Fang Chen
Affiliation:
Central Laboratory of the Institute of Molecular Technology for Drug Discovery and SynthesisDepartment of Applied Biology and Chemical TechnologyThe Hong Kong Polytechnic UniversityHung HomKowloonHong Kong SARChina Department of PhysiologyMedical College of Qingdao UniversityQingdao 266021China
Man-Sau Wong*
Affiliation:
Central Laboratory of the Institute of Molecular Technology for Drug Discovery and SynthesisDepartment of Applied Biology and Chemical TechnologyThe Hong Kong Polytechnic UniversityHung HomKowloonHong Kong SARChina State Key Laboratory of Chinese Medicine and Molecular PharmacologyShenzhenChina
*
*Corresponding author: Dr Man-Sau Wong, fax +852 23649932, email bcmswong@polyu.edu.hk
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Abstract

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Genistein and parathyroid hormone (PTH) are anabolic agents that stimulate bone formation through their direct actions in osteoblastic cells. In the present study, we aimed to determinewhether genistein modulates the actions of PTH in human osteoblastic SaOS-2 cells in an oestrogen-depleted condition. The present results showed that genistein (10−8 to 10−6 m) induced alkaline phosphatase (ALP) activity and osteoprotegrin (OPG) expression in SaOS-2 cells in a dose-dependent manner. These effects could be completely abolished by co-treatment with oestrogen antagonist ICI 182780 (7α-[9-[(4,4,5,5,5-pentafluoropentyl)sulfonyl]nonyl]-estra-1,3,5(10)-triene-3,17β-diol). Genistein (at 1μm) could stimulate the mRNA expression of receptor activator of NF-κB ligand (RANKL). As OPG and RANKL are known to modulate osteoclastogenesis, the ability of genistein to modulate OPG and RANKL expression in SaOS-2 cells suggested that it might modulate osteoclastogenesis through its direct actions on osteoblastic cells. PTH (at 10nm) stimulated ALP activity, induced RANKL mRNA expression and suppressed OPG mRNA expression in SaOS-2 cells, confirming its bi-directional effects on osteoblastic cells. Pre-treatment of SaOS-2 cells with genistein andoestrogen not only enhanced PTH-induced ALP activity, but also attenuated PTH up regulation ofRANKL mRNA expression and PTH down regulation of OPG mRNA expression. Taken together, the present study provides the first evidence that genistein could modulate the actions of PTH in human osteoblastic SaOS-2 cells in an oestrogen-depleted condition.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2006

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