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 ≤ 10 μm for 24 h did not affect the cell morphology or viability. However, treatment of MC3T3-E1 cells with 10 μm-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.

• Authors: Mei-Hsiu Liao, Yu-Ting Tai, Yih-Giun Cherng, Shing-Hwa Liu, Ya-An Chang, Pei-I Lin, Ruei-Ming Chen
• Journal: The British journal of nutrition (Br J Nutr) Vol. 111 Issue 1 Pg. 55-63 (Jan 14 2014) ISSN: 1475-2662 [Electronic] England
• PMID: 23829885 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bone Morphogenetic Protein 6
• Collagen Type I
• Estrogen Receptor alpha
• NF-kappa B
• Phytoestrogens
• Plant Extracts
• RNA, Messenger
• Transcription Factor AP-1
• Osteocalcin
• Genistein
• Mitogen-Activated Protein Kinases

Topics

• 3T3 Cells
• Animals
• Bone Morphogenetic Protein 6 (genetics, metabolism)
• Cell Differentiation (drug effects, genetics)
• Collagen Type I (genetics, metabolism)
• Dose-Response Relationship, Drug
• Estrogen Receptor alpha (genetics, metabolism)
• Fabaceae (chemistry)
• Gene Expression (drug effects)
• Gene Expression Regulation (drug effects)
• Genistein (pharmacology)
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Osteoblasts (drug effects, metabolism)
• Osteocalcin (genetics, metabolism)
• Osteogenesis (drug effects, genetics)
• Phosphorylation
• Phytoestrogens (pharmacology)
• Plant Extracts (pharmacology)
• Promoter Regions, Genetic
• RNA, Messenger (metabolism)
• Rats
• Transcription Factor AP-1 (metabolism)