title: Wasf2: a novel target of intermittent parathyroid hormone administration.
abstract: Systemic intermittent administration of parathyroid hormone (PTH) stimulates bone formation in animals and humans, and recombinant human PTH1-34 (teriparatide) is used clinically for the treatment of osteoporosis. In this study, we investigated the regulation of gene expression by intermittent PTH administration in MC3T3-E1 osteoblastic cells. We found that intermittent PTH1-34 administration downregulated Wiskott-Aldrich syndrome protein family member (Wasf) 2 mRNA expression. Wnt inhibitor, IWP-2, and protein kinase C inhibitor, Go6976, inhibited this downregulation. However, continuous PTH did not affect Wasf2 expression. Transfection of Wasf2 siRNA reduced bone sialoprotein (BSP) mRNA expression in a similar manner following intermittent PTH administration in MC3T3-E1 cells. These results identify Wasf2 as a novel target of intermittent PTH administration via the Wnt and phosphoinositide-dependent protein kinase signaling pathways, and the resulting regulation of BSP expression may contribute to the anabolic effects of PTH.
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Uyama
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Kawanami
authors.forename: Masato
authors.initials: M
authors.lastname: Tamura
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D010281:Parathyroid Hormone / Q000008:administration & dosage* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051785:Smad Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D051785:Smad Proteins; C492303:Wasf2 protein, mouse; D051300:Wiskott-Aldrich Syndrome Protein Family; D051153:Wnt Proteins