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

86 Citations (Scopus)

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

Fingerprint

CD40 Ligand
Stromal Cells
Parathyroid Hormone
T-Lymphocytes
Hyperparathyroidism
Mesenchymal Stromal Cells
Bone and Bones
Bone Diseases
Osteoclasts
Bone Resorption
Cytoplasmic and Nuclear Receptors
Cues
Cell Count
Cell Proliferation
Cortical Bone
Pharmacology
Ligands

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Gao, Y., Wu, X., Terauchi, M., Li, J. Y., Grassi, F., Galley, S., ... 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

T Cells Potentiate PTH-Induced Cortical Bone Loss through CD40L Signaling. / Gao, Yuhao; Wu, Xiaojun; Terauchi, Masakazu; Li, Jau Yi; Grassi, Francesco; Galley, Sarah; Yang, Xiaoying; Weitzmann, M. Neale; Pacifici, Roberto.

In: Cell Metabolism, Vol. 8, No. 2, 06.08.2008, p. 132-145.

Research output: Contribution to journalArticle

Gao, Y, Wu, X, Terauchi, M, Li, JY, Grassi, F, Galley, S, Yang, X, Weitzmann, MN & Pacifici, R 2008, 'T Cells Potentiate PTH-Induced Cortical Bone Loss through CD40L Signaling', Cell Metabolism, vol. 8, no. 2, pp. 132-145. https://doi.org/10.1016/j.cmet.2008.07.001
Gao, Yuhao ; Wu, Xiaojun ; Terauchi, Masakazu ; Li, Jau Yi ; Grassi, Francesco ; Galley, Sarah ; Yang, Xiaoying ; Weitzmann, M. Neale ; Pacifici, Roberto. / T Cells Potentiate PTH-Induced Cortical Bone Loss through CD40L Signaling. In: Cell Metabolism. 2008 ; Vol. 8, No. 2. pp. 132-145.
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