T Lymphocytes Amplify the Anabolic Activity of Parathyroid Hormone through Wnt10b Signaling

Masakazu Terauchi, Jau Yi Li, Brahmchetna Bedi, Ki Hyun Baek, Hesham Tawfeek, Sarah Galley, Linda Gilbert, Mark S. Nanes, Majd Zayzafoon, Robert Guldberg, David L. Lamar, Meredith A. Singer, Timothy F Lane, Henry M. Kronenberg, M. Neale Weitzmann, Roberto Pacifici*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

138 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)229-240
Number of pages12
JournalCell Metabolism
Volume10
Issue number3
DOIs
StatePublished - Sep 2 2009

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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