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Effects of 17β-estradiol on adiponectin regulation of the expression of osteoprotegerin and receptor activator of nuclear factor-κB ligand.
- Source :
-
Bone [Bone] 2012 Sep; Vol. 51 (3), pp. 515-23. Date of Electronic Publication: 2012 May 23. - Publication Year :
- 2012
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Abstract
- Adiponectin may exert a negative effect on bone metabolism by regulating osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) expression. However, the action of adiponectin on bone may be influenced by estrogen in women. The present study was undertaken to investigate the effects of 17β-estradiol (E2) on adiponectin-regulated OPG and RANKL expression in human osteoblast. Human osteoblasts were treated with α-MEM containing 10μg/ml adiponectin alone or together with 10(-10) to 10(-8)M E2 for 12-48h. Cells were also treated with α-MEM containing 10μg/ml adiponectin together with 10(-8)M E2 plus p38 agonist-anisomycin or estrogen receptor (ER) antagonist ICI182780 for 48h. The effects of E2 were also investigated by knockdown of ERs or overexpression of p38 MAPK in osteoblasts. Further, we examined the effects of E2 on adiponectin-dependent osteoclastogenesis by the co-culture systems of osteoblast and CD14+ peripheral blood monocytes (PBMCs). Real-time quantitative PCR (RT-PCR) and ELISA were used to detect OPG/RANKL mRNA and their corresponding protein expression, Western Blot was used to analyze the phosphorylated p38 (p-p38) levels. The results showed that E2 blocked adiponectin-induced p38 phosphorylation, decreased adiponectin-regulated OPG/RANKL mRNA and protein expression in a dose- and time-dependent manner. ICI182780 or knockdown of ERs abolished the effects of E2 on adiponectin-dependent p38 phosphorylation and OPG/RANKL expression. Furthermore, anisomycin or overexpression of p38 also reserved the effects of E2 on adiponectin-dependent p38 phosphorylation and OPG/RANKL expression. E2 inhibited adiponectin-dependent osteoclastogenesis in the co-culture systems of osteoblast and CD14+ PBMCs, whereas anisomycin, ICI182780, knockdown of ERs and overexpression of p38 significantly reversed this response. In conclusions, our findings demonstrated, through blocking the activation of adiponectin-induced p38 MAPK, E2 suppressed the adiponectin-regulated OPG/RANKL expression and then inhibited osteoclastogenesis, which suggested that estrogen would suppress the effect of adiponectin on bone metabolism.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Anisomycin pharmacology
Coculture Techniques
Enzyme Activation drug effects
Estradiol analogs & derivatives
Female
Fulvestrant
Humans
Leukocytes, Mononuclear metabolism
Lipopolysaccharide Receptors metabolism
MAP Kinase Signaling System drug effects
Osteoblasts drug effects
Osteoblasts enzymology
Osteogenesis drug effects
Osteogenesis genetics
Osteoprotegerin metabolism
RANK Ligand metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
Receptors, Estrogen metabolism
Time Factors
p38 Mitogen-Activated Protein Kinases metabolism
Adiponectin pharmacology
Estradiol pharmacology
Gene Expression Regulation drug effects
Osteoprotegerin genetics
RANK Ligand genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2763
- Volume :
- 51
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Bone
- Publication Type :
- Academic Journal
- Accession number :
- 22634178
- Full Text :
- https://doi.org/10.1016/j.bone.2012.05.011