Silencing of parathyroid hormone (PTH) receptor 1 in T cells blunts the bone anabolic activity of PTH

• Authors: Brahmchetna Bedi, Emory University; Jau-Yi Li, Emory University; Hesham Tawfeek, Emory University; Ki-Hyun Baek, Emory University; Jonathan Adams, Emory University; Sameera S. Vangara, Emory University; Ming-Kang Chang, Novartis Institutes for Biomedical Research; Michaela Kneissel, Novartis Institutes for Biomedical Research; M Neale Weitzmann, Emory University; Roberto Pacifici, Emory University
• Journal Title: Proceedings of the National Academy of Sciences
• Volume: Volume 109, Number 12
• Publisher: National Academy of Sciences | 2012-03-20, Pages E725-E733
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1073/pnas.1120735109
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: bone mass; T lymphocytes; bone cells

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.