Abstract
A protective effect of plant extract from Onobrychis ebenoides on ovariectomy-induced bone loss in rats has been shown. To investigate the molecular mechanisms that underly the beneficial effect of O. ebenoides (Onb) on bone loss, we studied its potential to activate ER subtypes (ERalpha and ERbeta) on transiently transfected HeLa cells with HO-hERalpha or pSG5-hERbeta and 3xERE-TATA-Luc expression vectors. Its impact to stimulate differentiation and mineralization of osteoblasts (KS483 cell line) by Alizarin Red-S staining was also examined. Furthermore we sought to induce for its potential the IGFBP3, a known estrogen-dependent marker in MCF7 breast cancer cells. 17beta-Estradiol and the pure antiestrogen ICI182780 were included to serve as control samples of the estrogenic and antiestrogenic activity respectively. Our data revealed: (1) Onb extract displayed a significant estrogenic activity on both ERalpha and ERbeta subtypes. (2) It exhibited direct action on osteoblasts by inducing mineralization. (3) It showed estrogenic activity in MCF7 cells. These findings suggest that the beneficial effect of Onb extract on bone loss is mediated through an estrogen-like action via activation of ERalpha-ERE and ERbeta-ERE pathways and via direct action on the mineralization process of osteoblasts.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Breast Neoplasms / drug therapy
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Breast Neoplasms / metabolism
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Calcification, Physiologic / drug effects
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Estradiol / analogs & derivatives
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Estradiol / pharmacology
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Estrogen Antagonists / pharmacology*
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Estrogen Receptor alpha / drug effects*
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Estrogen Receptor alpha / genetics
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Estrogen Receptor alpha / metabolism
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Estrogen Receptor beta / drug effects*
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Estrogen Receptor beta / genetics
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Estrogen Receptor beta / metabolism
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Fabaceae / chemistry*
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Female
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Fulvestrant
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Genes, Reporter
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HeLa Cells / drug effects
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HeLa Cells / metabolism
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HeLa Cells / pathology
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Humans
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Insulin-Like Growth Factor Binding Protein 3
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Insulin-Like Growth Factor Binding Proteins / metabolism
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Luciferases / genetics
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Luciferases / metabolism
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Osteoblasts / drug effects
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Osteoblasts / metabolism
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Osteoblasts / pathology
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Phytoestrogens / pharmacology*
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Plant Extracts / chemistry
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Plant Extracts / pharmacology*
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Response Elements / drug effects
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Response Elements / genetics
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Transfection
Substances
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Estrogen Antagonists
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Estrogen Receptor alpha
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Estrogen Receptor beta
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IGFBP3 protein, human
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Insulin-Like Growth Factor Binding Protein 3
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Insulin-Like Growth Factor Binding Proteins
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Phytoestrogens
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Plant Extracts
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Fulvestrant
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Estradiol
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Luciferases