Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-α
Simone Cenci, M. Neale Weitzmann, Cristiana Roggia, Noriyuki Namba, Deborah Novack, Jessica Woodring, Roberto Pacifici
Simone Cenci, M. Neale Weitzmann, Cristiana Roggia, Noriyuki Namba, Deborah Novack, Jessica Woodring, Roberto Pacifici
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Article

Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-α

Abstract

Estrogen 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.

Authors

Simone Cenci, M. Neale Weitzmann, Cristiana Roggia, Noriyuki Namba, Deborah Novack, Jessica Woodring, Roberto Pacifici

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Ovariectomy fails to increase osteoclast formation in cultures of bone m...
Ovariectomy fails to increase osteoclast formation in cultures of bone marrow cells from nude mice. Mean (± SEM) number of osteoclasts from three independent experiments (n = 6 wells per group). AP < 0.05 compared to estrogen replete mice. (a) Unfractionated bone marrow cells (106 cells/well) from OVX and estrogen-replete nude and euthymic mice were harvested 4 weeks after surgery and cultured for 7 days with 1,25(OH)2D3 (10–8M) to induce osteoclast formation. (b) Bone marrow cells were depleted of stromal cells by adherence for 12 hours. Nonadherent bone marrow cells (106 cells/well) were cultured for 7 days with optimal osteoclastogenic concentrations of M-CSF (25 ng/ml) and RANKL (100 ng/ml). OC, osteoclast.