title: Silencing of parathyroid hormone (PTH) receptor 1 in T cells blunts the bone anabolic activity of PTH.
abstract: Intermittent parathyroid hormone (iPTH) treatment stimulates T-cell production of the osteogenic Wnt ligand Wnt10b, a factor required for iPTH to activate Wnt signaling in osteoblasts and stimulate bone formation. However, it is unknown whether iPTH induces Wnt10b production and bone anabolism through direct activation of the parathyroid hormone (PTH)/PTH-related protein receptor (PPR) in T cells. Here, we show that conditional silencing of PPR in T cells blunts the capacity of iPTH to induce T-cell production of Wnt10b; activate Wnt signaling in osteoblasts; expand the osteoblastic pool; and increase bone turnover, bone mineral density, and trabecular bone volume. These findings demonstrate that direct PPR signaling in T cells plays an important role in PTH-induced bone anabolism by promoting T-cell production of Wnt10b and suggest that T cells 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: Brahmchetna
authors.initials: B
authors.lastname: Bedi
authors.forename: Jau-Yi
authors.initials: JY
authors.lastname: Li
authors.forename: Hesham
authors.initials: H
authors.lastname: Tawfeek
authors.forename: Ki-Hyun
authors.initials: KH
authors.lastname: Baek
authors.forename: Jonathan
authors.initials: J
authors.lastname: Adams
authors.forename: Sameera S
authors.initials: SS
authors.lastname: Vangara
authors.forename: Ming-Kang
authors.initials: MK
authors.lastname: Chang
authors.forename: Michaela
authors.initials: M
authors.lastname: Kneissel
authors.forename: M Neale
authors.initials: MN
authors.lastname: Weitzmann
authors.forename: Roberto
authors.initials: R
authors.lastname: Pacifici
mesh_terms: D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism*; D005260:Female; D020868:Gene Silencing; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D010006:Osteoblasts / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D008024:Ligands; D010281:Parathyroid Hormone; D011518:Proto-Oncogene Proteins; D044168:Receptor, Parathyroid Hormone, Type 1; C491119:WNT10B protein, human; D051153:Wnt Proteins