Simone Cenci, M. Neale Weitzmann, Cristiana Roggia, Noriyuki Namba, Deborah Novack, Jessica Woodring, Roberto Pacifici
J Clin Invest.
2000;
106(10):1229–1237
doi:10.1172/JCI11066
This article Copyright © 2000, The American Society for Clinical Investigation
Abstract
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strogen deficiency induces bone loss by upregulating osteoclastogenesis by mechanisms not completely defined. We found that ovariectomy-enhanced T-cell production of TNF-α, which, acting through the TNF-α receptor p55, augments macrophage colony-stimulating factor–induced (M-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-α, is a key mechanism by which estrogen prevents osteoclastic bone resorption and bone loss.
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