T Cells Potentiate PTH-Induced Cortical Bone Loss through CD40L Signaling

Yuhao Gao, Xiaojun Wu, Masakazu Terauchi, Jau Yi Li, Francesco Grassi, Sarah Galley, Xiaoying Yang, M. Neale Weitzmann, Roberto Pacifici

Research output: Contribution to journalArticle

Abstract

Parathyroid hormone (PTH) promotes bone catabolism by targeting bone marrow (BM) stromal cells (SCs) and their osteoblastic progeny. Here we show that a continuous infusion of PTH that mimics hyperparathyroidism fails to induce osteoclast formation, bone resorption, and cortical bone loss in mice lacking T cells. T cells provide proliferative and survival cues to SCs and sensitize SCs to PTH through CD40 ligand (CD40L), a surface molecule of activated T cells that induces CD40 signaling in SCs. As a result, deletion of T cells or T cell-expressed CD40L blunts the bone catabolic activity of PTH by decreasing bone marrow SC number, the receptor activator of nuclear factor-κB ligand (RANKL)/OSTEOPROTEGERN (OPG) ratio, and osteoclastogenic activity. Therefore, T cells play an essential permissive role in hyperparathyroidism as they influence SC proliferation, life span, and function through CD40L. T cell-SC crosstalk pathways may thus provide pharmacological targets for PTH-induced bone disease.

Original languageEnglish
Pages (from-to)132-145
Number of pages14
JournalCell Metabolism
Volume8
Issue number2
DOIs
Publication statusPublished - Aug 6 2008

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

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    Gao, Y., Wu, X., Terauchi, M., Li, J. Y., Grassi, F., Galley, S., Yang, X., Weitzmann, M. N., & Pacifici, R. (2008). T Cells Potentiate PTH-Induced Cortical Bone Loss through CD40L Signaling. Cell Metabolism, 8(2), 132-145. https://doi.org/10.1016/j.cmet.2008.07.001