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Author Notes:

Correspondence: Roberto Pacifici, M.D., Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, 101 Woodruff Circle, Room 1309, Atlanta, GA 30322; Telephone: 404-712-8420; Fax: 404-727-1300; Email: roberto.pacifici@emory.edu

We are grateful to Dr. Laurie McCauley at Michigan University and Dr. Gilbert Kersh at Emory University for their suggestions and review of the manuscript, and


Research Funding:

This study was supported, in part, by grants from the National Institutes of Health (AR54625 and AG28278) and the University Research Committee of Emory University. NMW was supported in part by grants from the National Institutes of Health (AR053607 and DK067389), and the University Research Committee of Emory University.

We are grateful to the University of Alabama at Birmingham, Center for Metabolic Bone Disease-Histomorphometry and Molecular Analysis Core Laboratory, NIH Grant P30-AR46031 for the histomorphometric analysis presented herein

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


Journal Title:

Cell Metabolism


Volume 8, Number 2


, Pages 132-145

Type of Work:

Article | Post-print: After Peer Review


PTH promotes bone catabolism by targeting bone marrow 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, RANKL/OPG production and osteoclastogenic activity. Therefore, T cells play an essential permissive role in hyperparathyroidism as they influence SC proliferation, lifespan and function through CD40L. T cell-SC cross-talk pathways may thus provide pharmacological targets for PTH induced bone disease.

Copyright information:

© 2008, Elsevier

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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