title: PTH regulates β2-adrenergic receptor expression in osteoblast-like MC3T3-E1 cells.
abstract: 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 1 nM. 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.
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical & Dental University, Japan; Department of Orthopaedic Surgery, Juntendo University School of Medicine, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Moriya
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Hayata
authors.forename: Takuya
authors.initials: T
authors.lastname: Notomi
authors.forename: Smriti
authors.initials: S
authors.lastname: Aryal
authors.forename: Testuya
authors.initials: T
authors.lastname: Nakamaoto
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Izu
authors.forename: Makiri
authors.initials: M
authors.lastname: Kawasaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamada
authors.forename: Jumpei
authors.initials: J
authors.lastname: Shirakawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kaneko
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ezura
authors.forename: Masaki
authors.initials: M
authors.lastname: Noda
mesh_terms: D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D010281:Parathyroid Hormone; D016760:Proto-Oncogene Proteins c-fos; D018343:Receptors, Adrenergic, beta-2; D005576:Colforsin; D000242:Cyclic AMP
keywords: ADRENERGIC; BONE; PTH