PTH Regulates [beta]2-Adrenergic Receptor Expression in Osteoblast-Like MC3T3-E1 Cells

• Published in: Journal of cellular biochemistry 2015-01, Vol.116 (1), p.142
• Main Authors: Moriya, Shuichi, Hayata, Tadayoshi, Notomi, Takuya, Aryal, Smriti, Nakamaoto, Testuya, Izu, Yayoi, Kawasaki, Makiri, Yamada, Takayuki, Shirakawa, Jumpei, Kaneko, Kazuo, Ezura, Yoichi, Noda, Masaki
• Format: Article
• Language: English
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.24953

As the aged population is soaring, prevalence of osteoporosis is increasing. However, the molecular basis underlying the regulation of bone mass is still incompletely understood. Sympathetic tone acts via beta2 adrenergic receptors in bone and regulates the mass of bone which is the target organ of parathyroid hormone (PTH). However, whether beta2 adrenergic receptor is regulated by PTH in bone cells is not known. We therefore investigated the effects of PTH on beta2 adrenergic receptor gene expression in osteoblast-like MC3T3-E1 cells. PTH treatment immediately suppressed the expression levels of beta2 adrenergic receptor mRNA. This PTH effect was dose-dependent starting as low as 1nM. PTH action on beta2 adrenergic receptor gene expression was inhibited by a transcriptional inhibitor, DRB, but not by a protein synthesis inhibitor, cycloheximide suggesting direct transcription control. Knockdown of beta2 adrenergic receptor promoted PTH-induced expression of c-fos, an immediate early response gene. With respect to molecular basis for this phenomenon, knockdown of beta2 adrenergic receptor enhanced PTH-induced transcriptional activity of cyclic AMP response element-luciferase construct in osteoblasts. Knockdown of beta2 adrenergic receptors also enhanced forskolin-induced luciferase expression, revealing that adenylate cyclase activity is influenced by beta2 adrenergic receptor. As for phosphorylation of transcription factor, knockdown of beta2 adrenergic receptor enhanced PTH-induced phosphorylation of cyclic AMP response element binding protein (CREB). These data reveal that beta2 adrenergic receptor is one of the targets of PTH and acts as a suppressor of PTH action in osteoblasts. J. Cell. Biochem. 116: 142-148, 2015. © 2014 Wiley Periodicals, Inc.