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Published on: November 6, 2014
Functional alpha1- and beta2-adrenergic receptors in human osteoblasts
H H Huang1, T C Brennan, M M Muir
1Department of Physiology, School of Medical Sciences, University of Sydney, Sydney, NSW, Australia.
Journal of Cellular Physiology
|April 1, 2009
Summary
Human bone cells express functional alpha1- and beta2-adrenergic receptors (ARs). These receptors, alpha1-ARs and beta2-ARs, influence human osteoblast replication and the expression of RANKL and OPG, impacting bone turnover.
Area of Science:
- Endocrinology
- Bone Biology
- Adrenergic Signaling
Background:
- Central control of bone mass is linked to beta2-adrenergic receptors (beta2-ARs).
- Expression and function of alpha-ARs in human bone cells remain controversial.
- Previous studies in mice suggest adrenergic regulation of RANKL and OPG mRNA.
Purpose of the Study:
- To investigate the expression of alpha1-AR and beta2-AR mRNA and protein in human osteoblasts (HOBs).
- To determine the functional role of adrenergic stimulation on HOB proliferation, RANKL, and OPG expression.
- To clarify the presence and role of alpha-ARs in human bone cells.
Main Methods:
- RT-PCR for mRNA expression of alpha1B- and beta2-ARs.
- Immunofluorescence microscopy and Western blot for protein localization and identification.
- Cell proliferation assays using (3)H-thymidine incorporation.
- Quantitative RT-PCR for RANKL and OPG mRNA levels.
- siRNA knockdown of alpha1B-ARs.
Main Results:
- Both alpha1B- and beta2-AR mRNA were detected in HOBs and MG63 cells.
- Immunofluorescence and Western blot confirmed alpha1B- and beta2-ARs in HOBs.
- Alpha1-agonists and propranolol increased HOB proliferation, while a beta2-agonist inhibited it.
- Beta2-agonist stimulation increased RANKL mRNA, inhibited by propranolol.
- Alpha1-agonist stimulation increased OPG mRNA, abolished by alpha1B-AR knockdown.
Conclusions:
- Human osteoblasts express functional alpha1- and beta2-adrenergic receptors.
- Adrenergic signaling, via both alpha1-ARs and beta2-ARs, modulates human osteoblast proliferation.
- Alpha1-ARs and beta2-ARs play distinct roles in regulating RANKL and OPG expression in human bone cells.
- Alpha1-ARs may contribute to sympathetic nervous system regulation of bone turnover in humans.
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