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

Brahmchetna Bedi, Jau Yi Li, Hesham Tawfeek, Ki Hyun Baek, Jonathan Adams, Sameera S. Vangara, Ming Kang Chang, Michaela Kneissel, M. Neale Weitzmann, Roberto Pacifici

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)E725-E733
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
StatePublished - Mar 20 2012
Externally publishedYes


  • Bone cells
  • Bone mass
  • T lymphocytes

ASJC Scopus subject areas

  • General


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