Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 106, Issue 10, Pages 1229-1237Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI11066
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- NIAMS NIH HHS [AR-41412, R01 AR041412, AR-13534] Funding Source: Medline
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Estrogen deficiency induces bone loss by upregulating osteoclastogenesis by mechanisms not completely defined. We found that ovariectomy-enhanced T-cell production of TNF-alpha, which, acting through the TNF-a receptor p55, augments macrophage colony-stimulating factor-induced (hl-CSF-induced) and RANKL-induced osteoclastogenesis. Ovariectomy failed to induce bone loss, stimulate bone resorption, or increase M-CSF- and RANKL-dependent osteoclastogenesis in T-cell deficient mice, establishing T cells as essential mediators of the bone-wasting effects of estrogen deficiency in vivo. These findings demonstrate that the ability of estrogen to target T cells, suppressing their production of TNF-alpha, is a key mechanism by which estrogen prevents osteoclastic bone resorption and bone loss.
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