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

    Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):768-73. Epub 2010 Dec 27.

    These authors find that CD40 ligand, which regulates T-lymphocyte function, is necessary for estrogen withdrawal to promote bone loss in mice.

    Authors: Li JY, Tawfeek H, Bedi B, et. al

    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.

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