title: Regulation of neuropeptide Y Y1 receptor expression by bone morphogenetic protein 2 in C2C12 myoblasts.
abstract: The neuropeptide Y (NPY) system is known as one of the major neural signaling pathways. NPY, produced by peripheral tissues including osteoblasts, is known to bind to the Y1 receptor. Recently, osteoblast-specific Y1 receptor knockout mice were developed and were found to have a high bone mass phenotype, indicating a role for the NPY-Y1 receptor axis as a regulator of bone homeostasis. However, regulation of Y1 receptor expression during osteoblastic differentiation remains unexplored. In the present study, we examined the role of bone morphogenetic protein (BMP) 2 signaling in regulating Y1 receptor expression. In C2C12 cells, expression of Y1 receptor mRNA was induced by BMP2. This induction was also observed after co-transfection with Smad1 and Smad4, the intracellular signaling molecules of the BMP2 signaling pathway. In a transfection assay, Smad1/4 up-regulated transcriptional activity through interaction with the Y1 receptor gene promoter. Following transfection of MC3T3-E1 cells with siRNA for the Y1 receptor, the expression of alkaline phosphatase, osteocalcin, Runx2 and osterix were increased. These results show that BMP2 signaling regulates Y1 receptor gene expression, and raises the possibility that NPY acts in osteoblasts via an autocrine mechanism.
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan; Department of Dental Anesthesiology, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kurebayashi
authors.forename: Mari
authors.initials: M
authors.lastname: Sato
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Fukushima
authors.forename: Masato
authors.initials: M
authors.lastname: Tamura
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D051379:Mice; D032446:Myoblasts / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; C097212:neuropeptide Y-Y1 receptor
keywords: Bone morphogenetic protein 2; Neuropeptide Y; Osteoblasts; Y1 receptor