Genistein induces oestrogen receptor-α gene expression in osteoblasts through the activation of mitogen-activated protein kinases/NF-κB/ activator protein-1 and promotes cell mineralisation

Mei Hsiu Liao, Yu-Ting Tai, Yih-Giun Cherng, Shing Hwa Liu, Ya An Chang, Pei I. Lin, Ruei-Ming Chen

研究成果: 雜誌貢獻文章

25 引文 (Scopus)

摘要

Oestrogen and oestrogen receptors (ER) play critical roles in the maintenance of bone remodelling. Genistein, structurally similar to 17β-oestradiol, is a phyto-oestrogen that may be beneficial for treating osteoporosis. In the present study, we evaluated the effects of genistein on the regulation of ERα gene expression and osteoblast mineralisation using MC3T3-E1 cells and primary rat calvarial osteoblasts as our experimental models. Exposure of MC3T3-E1 cells and primary rat osteoblasts to genistein at ≤10μm for 24h did not affect the cell morphology or viability. However, treatment of MC3T3-E1 cells with 10μm-genistein enhanced the phosphorylation of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase 1/2 in a time-dependent manner. Sequentially, genistein increased the translocation of NF-κB and c-Jun from the cytoplasm to the nucleus. Consequently, exposure of MC3T3-E1 cells to genistein induced ERα mRNA expression in concentration-and time-dependent manners. In parallel, the amounts of cytosolic and nuclear ERα in MC3T3-E1 cells were increased following genistein administration. Additionally, genistein also increased the levels of ERα mRNA and nuclear ERα protein in rat calvarial osteoblasts. A bioinformatic search revealed that there are several ERα-specific DNA-binding elements in the 5′-promoter regions of the bone morphogenetic protein-6, collagen type I and osteocalcin genes. As a result, genistein could induce the expressions of these osteoblast differentiation-related genes in primary rat osteoblasts. Co-treatment with genistein and traditional differentiation reagents synergistically increased osteoblast mineralisation. Therefore, the present study showed that genistein can induce ERα gene expression via the activation of MAPK/NF-κB/ activator protein-1 and accordingly stimulates differentiation-related gene expressions and osteoblast mineralisation.
原文英語
頁(從 - 到)55-63
頁數9
期刊British Journal of Nutrition
111
發行號1
DOIs
出版狀態已發佈 - 一月 14 2014

指紋

Proto-Oncogene Proteins c-akt
Genistein
Transcription Factor AP-1
Mitogen-Activated Protein Kinases
Osteoblasts
Estrogen Receptors
Gene Expression
Bone Morphogenetic Protein 6
Mitogen-Activated Protein Kinase 9
Mitogen-Activated Protein Kinase 8
Phytoestrogens
Messenger RNA
Mitogen-Activated Protein Kinase 3
Bone Remodeling
Mitogen-Activated Protein Kinase 1
Osteocalcin
Gene Expression Regulation
p38 Mitogen-Activated Protein Kinases
Nuclear Proteins
Collagen Type I

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

引用此文

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title = "Genistein induces oestrogen receptor-α gene expression in osteoblasts through the activation of mitogen-activated protein kinases/NF-κB/ activator protein-1 and promotes cell mineralisation",
abstract = "Oestrogen and oestrogen receptors (ER) play critical roles in the maintenance of bone remodelling. Genistein, structurally similar to 17β-oestradiol, is a phyto-oestrogen that may be beneficial for treating osteoporosis. In the present study, we evaluated the effects of genistein on the regulation of ERα gene expression and osteoblast mineralisation using MC3T3-E1 cells and primary rat calvarial osteoblasts as our experimental models. Exposure of MC3T3-E1 cells and primary rat osteoblasts to genistein at ≤10μm for 24h did not affect the cell morphology or viability. However, treatment of MC3T3-E1 cells with 10μm-genistein enhanced the phosphorylation of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase 1/2 in a time-dependent manner. Sequentially, genistein increased the translocation of NF-κB and c-Jun from the cytoplasm to the nucleus. Consequently, exposure of MC3T3-E1 cells to genistein induced ERα mRNA expression in concentration-and time-dependent manners. In parallel, the amounts of cytosolic and nuclear ERα in MC3T3-E1 cells were increased following genistein administration. Additionally, genistein also increased the levels of ERα mRNA and nuclear ERα protein in rat calvarial osteoblasts. A bioinformatic search revealed that there are several ERα-specific DNA-binding elements in the 5′-promoter regions of the bone morphogenetic protein-6, collagen type I and osteocalcin genes. As a result, genistein could induce the expressions of these osteoblast differentiation-related genes in primary rat osteoblasts. Co-treatment with genistein and traditional differentiation reagents synergistically increased osteoblast mineralisation. Therefore, the present study showed that genistein can induce ERα gene expression via the activation of MAPK/NF-κB/ activator protein-1 and accordingly stimulates differentiation-related gene expressions and osteoblast mineralisation.",
keywords = "Genistein, Mitogen-activated protein kinase mechanisms, Oestrogen receptor-α, Osteoblast mineralisation, Osteoblasts",
author = "Liao, {Mei Hsiu} and Yu-Ting Tai and Yih-Giun Cherng and Liu, {Shing Hwa} and Chang, {Ya An} and Lin, {Pei I.} and Ruei-Ming Chen",
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T1 - Genistein induces oestrogen receptor-α gene expression in osteoblasts through the activation of mitogen-activated protein kinases/NF-κB/ activator protein-1 and promotes cell mineralisation

AU - Liao, Mei Hsiu

AU - Tai, Yu-Ting

AU - Cherng, Yih-Giun

AU - Liu, Shing Hwa

AU - Chang, Ya An

AU - Lin, Pei I.

AU - Chen, Ruei-Ming

PY - 2014/1/14

Y1 - 2014/1/14

N2 - Oestrogen and oestrogen receptors (ER) play critical roles in the maintenance of bone remodelling. Genistein, structurally similar to 17β-oestradiol, is a phyto-oestrogen that may be beneficial for treating osteoporosis. In the present study, we evaluated the effects of genistein on the regulation of ERα gene expression and osteoblast mineralisation using MC3T3-E1 cells and primary rat calvarial osteoblasts as our experimental models. Exposure of MC3T3-E1 cells and primary rat osteoblasts to genistein at ≤10μm for 24h did not affect the cell morphology or viability. However, treatment of MC3T3-E1 cells with 10μm-genistein enhanced the phosphorylation of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase 1/2 in a time-dependent manner. Sequentially, genistein increased the translocation of NF-κB and c-Jun from the cytoplasm to the nucleus. Consequently, exposure of MC3T3-E1 cells to genistein induced ERα mRNA expression in concentration-and time-dependent manners. In parallel, the amounts of cytosolic and nuclear ERα in MC3T3-E1 cells were increased following genistein administration. Additionally, genistein also increased the levels of ERα mRNA and nuclear ERα protein in rat calvarial osteoblasts. A bioinformatic search revealed that there are several ERα-specific DNA-binding elements in the 5′-promoter regions of the bone morphogenetic protein-6, collagen type I and osteocalcin genes. As a result, genistein could induce the expressions of these osteoblast differentiation-related genes in primary rat osteoblasts. Co-treatment with genistein and traditional differentiation reagents synergistically increased osteoblast mineralisation. Therefore, the present study showed that genistein can induce ERα gene expression via the activation of MAPK/NF-κB/ activator protein-1 and accordingly stimulates differentiation-related gene expressions and osteoblast mineralisation.

AB - Oestrogen and oestrogen receptors (ER) play critical roles in the maintenance of bone remodelling. Genistein, structurally similar to 17β-oestradiol, is a phyto-oestrogen that may be beneficial for treating osteoporosis. In the present study, we evaluated the effects of genistein on the regulation of ERα gene expression and osteoblast mineralisation using MC3T3-E1 cells and primary rat calvarial osteoblasts as our experimental models. Exposure of MC3T3-E1 cells and primary rat osteoblasts to genistein at ≤10μm for 24h did not affect the cell morphology or viability. However, treatment of MC3T3-E1 cells with 10μm-genistein enhanced the phosphorylation of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase 1/2 in a time-dependent manner. Sequentially, genistein increased the translocation of NF-κB and c-Jun from the cytoplasm to the nucleus. Consequently, exposure of MC3T3-E1 cells to genistein induced ERα mRNA expression in concentration-and time-dependent manners. In parallel, the amounts of cytosolic and nuclear ERα in MC3T3-E1 cells were increased following genistein administration. Additionally, genistein also increased the levels of ERα mRNA and nuclear ERα protein in rat calvarial osteoblasts. A bioinformatic search revealed that there are several ERα-specific DNA-binding elements in the 5′-promoter regions of the bone morphogenetic protein-6, collagen type I and osteocalcin genes. As a result, genistein could induce the expressions of these osteoblast differentiation-related genes in primary rat osteoblasts. Co-treatment with genistein and traditional differentiation reagents synergistically increased osteoblast mineralisation. Therefore, the present study showed that genistein can induce ERα gene expression via the activation of MAPK/NF-κB/ activator protein-1 and accordingly stimulates differentiation-related gene expressions and osteoblast mineralisation.

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KW - Oestrogen receptor-α

KW - Osteoblast mineralisation

KW - Osteoblasts

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