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Author Notes:

To whom correspondence should be addressed. E-mail: roberto.pacifici@emory.edu.

Edited by John T. Potts, Massachusetts General Hospital, Charlestown, MA, and approved February 6, 2012 (received for review December 28, 2011)

Author contributions: M.N.W., and R.P. designed research; B.B., J.-Y.L., H.T., K.-H.B., M.-K.C., J.A., and M.K. performed research; B.B., J.-Y.L., S.S.V., M.-K.C., M.K., and R.P. analyzed data; and M.N.W. and R.P. wrote the paper.

B.B. and J.-Y.L. contributed equally to this work.

Subject:

Keywords:

  • bone mass
  • T lymphocytes
  • bone cells

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

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Journal Title:

Proceedings of the National Academy of Sciences

Volume:

Volume 109, Number 12

Publisher:

, Pages E725-E733

Type of Work:

Article | Post-print: After Peer Review

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.
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