Journal
CELL METABOLISM
Volume 8, Issue 2, Pages 132-145Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2008.07.001
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Funding
- NIAMS NIH HHS [AR053607, P30 AR046031, R21 AR053607, AR54625, R01 AR054625-02, R01 AR054625-01A1, P30-AR46031, R01 AR054625] Funding Source: Medline
- NIA NIH HHS [AG28278, R01 AG028278] Funding Source: Medline
- NIDDK NIH HHS [T32 DK007298, T32 DK007298-27, T32 DK007298-28, R21 DK067389, T32 DK007298-29, DK067389] Funding Source: Medline
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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-kappa B ligand (RANKL)/OSTEOPROTE GERN (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.
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