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Author Notes:

To whom correspondence should be addressed. E-mail: roberto.pacifici@emory.edu.

Edited by John T. Potts, Massachusetts General Hospital, Charlestown, MA, and approved November 30, 2010 (received for review September 9, 2010)

Author contributions: J.-Y.L., M.N.W., and R.P. designed research; J.-Y.L., H.T., B.B., X.Y., J.A., K.Y.G., and M.Z. performed research; X.Y., J.A., K.Y.G., M.N.W., and R.P. analyzed data; and J.-Y.L., M.N.W., and R.P. wrote the paper.


Research Funding:

This study was supported by the National Institutes of Health (Grants AR49659 and AG28278). M.N.W. is supported, in part, by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (Grants AR053607 and AR059364) and by a Veterans Affairs Merit Grant (5I01BX000105).


  • estrogen
  • osteoporosis

Ovariectomy disregulates osteoblast and osteoclast formation through the T-cell receptor CD40 ligand


Journal Title:

Proceedings of the National Academy of Sciences


Volume 108, Number 2


, Pages 768-773

Type of Work:

Article | Post-print: After Peer Review


The bone loss induced by ovariectomy (ovx) has been linked to increased production of osteoclastogenic cytokines by bone marrow cells, including T cells and stromal cells (SCs). It is presently unknown whether regulatory interactions between these lineages contribute to the effects of ovx in bone, however. Here, we show that the T-cell costimulatory molecule CD40 ligand (CD40L) is required for ovx to expand SCs; promote osteoblast proliferation and differentiation; regulate the SC production of the osteoclastogenic factors macrophage colony-stimulating factor, receptor activator of nuclear factor-κB ligand, and osteoprotegerin; and up-regulate osteoclast formation. CD40L is also required for ovx to activate T cells and stimulate their production of TNF. Accordingly, ovx fails to promote bone loss and increase bone resorption in mice depleted of T cells or lacking CD40L. Therefore, cross-talk between T cells and SCs mediated by CD40L plays a pivotal role in the disregulation of osteoblastogenesis and osteoclastogenesis induced by ovx.

Copyright information:

Beginning with articles submitted in Volume 106 (2009) the author(s) retains copyright to individual articles, and the National Academy of Sciences of the United States of America retains an exclusive license to publish these articles and holds copyright to the collective work.

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