title: T lymphocytes amplify the anabolic activity of parathyroid hormone through Wnt10b signaling.
abstract: Intermittent administration of parathyroid hormone (iPTH) is used to treat osteoporosis because it improves bone architecture and strength, but the underlying cellular and molecular mechanisms are unclear. Here, we show that iPTH increases the production of Wnt10b by bone marrow CD8+ T cells and induces these lymphocytes to activate canonical Wnt signaling in preosteoblasts. Accordingly, in responses to iPTH, T cell null mice display diminished Wnt signaling in preosteoblasts and blunted osteoblastic commitment, proliferation, differentiation, and life span, which result in decreased trabecular bone anabolism and no increase in strength. Demonstrating the specific role of lymphocytic Wnt10b, iPTH has no anabolic activity in mice lacking T-cell-produced Wnt10b. Therefore, T-cell-mediated activation of Wnt signaling in osteoblastic cells plays a key permissive role in the mechanism by which iPTH increases bone strength, suggesting that T cell osteoblast crosstalk pathways may provide pharmacological targets for bone anabolism.
authors.affiliation: Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Terauchi
authors.forename: Jau-Yi
authors.initials: JY
authors.lastname: Li
authors.forename: Brahmchetna
authors.initials: B
authors.lastname: Bedi
authors.forename: Ki-Hyun
authors.initials: KH
authors.lastname: Baek
authors.forename: Hesham
authors.initials: H
authors.lastname: Tawfeek
authors.forename: Sarah
authors.initials: S
authors.lastname: Galley
authors.forename: Linda
authors.initials: L
authors.lastname: Gilbert
authors.forename: Mark S
authors.initials: MS
authors.lastname: Nanes
authors.forename: Majd
authors.initials: M
authors.lastname: Zayzafoon
authors.forename: Robert
authors.initials: R
authors.lastname: Guldberg
authors.forename: David L
authors.initials: DL
authors.lastname: Lamar
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Singer
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Lane
authors.forename: Henry M
authors.initials: HM
authors.lastname: Kronenberg
authors.forename: M Neale
authors.initials: MN
authors.lastname: Weitzmann
authors.forename: Roberto
authors.initials: R
authors.lastname: Pacifici
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D010281:Parathyroid Hormone; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051153:Wnt Proteins; C102068:Wnt10b protein, mouse