title: β₂ adrenergic receptor activation suppresses bone morphogenetic protein (BMP)-induced alkaline phosphatase expression in osteoblast-like MC3T3E1 cells.
abstract: β adrenergic stimulation suppresses bone formation in vivo while its actions in osteoblastic differentiation are still incompletely understood. We therefore examined the effects of β2 adrenergic stimulation on osteoblast-like MC3T3-E1 cells focusing on BMP-induced alkaline phosphatase expression. Morphologically, isoproterenol treatment suppresses BMP-induced increase in the numbers of alkaline phosphatase-positive small foci in the cultures of MC3T3-E1 cells. Biochemically, isoproterenol treatment suppresses BMP-induced enzymatic activity of alkaline phosphatase in a dose-dependent manner. Isoproterenol suppression of alkaline phosphatase activity is observed even when the cells are treated with high concentrations of BMP. With respect to cell density, isoproterenol treatment tends to suppress BMP-induced increase in alkaline phosphatase expression more in osteoblasts cultured at higher cell density. In terms of treatment protocol, continuous isoproterenol treatment is compared to cyclic treatment. Continuous isoproterenol treatment is more suppressive against BMP-induced increase in alkaline phosphatase expression than cyclic regimen. At molecular level, isoproterenol treatment suppresses BMP-induced enhancement of alkaline phosphatase mRNA expression. Regarding the mode of isoproterenol action, isoproterenol suppresses BMP-induced BRE-luciferase activity. These data indicate that isoproterenol regulates BMP-induced alkaline phosphatase expression in osteoblast-like MC3T3E1 cells.
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan; Department of Oral and Maxillofacial Surgery, Tokyo Medical and Dental University, Tokyo, Japan; Global COE Program, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamada
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ezura
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Hayata
authors.forename: Shuichi
authors.initials: S
authors.lastname: Moriya
authors.forename: Jumpei
authors.initials: J
authors.lastname: Shirakawa
authors.forename: Takuya
authors.initials: T
authors.lastname: Notomi
authors.forename: Smriti
authors.initials: S
authors.lastname: Arayal
authors.forename: Makiri
authors.initials: M
authors.lastname: Kawasaki
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Izu
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Harada
authors.forename: Masaki
authors.initials: M
authors.lastname: Noda
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D011941:Receptors, Adrenergic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D019485:Bone Morphogenetic Proteins; D011941:Receptors, Adrenergic; D000469:Alkaline Phosphatase
keywords: ALKALINE PHOSPHATASE; BMP; ISOPROTERENOL; OSTEOBLAST