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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T cells from OVX mice fail to increase RANKL- and M-CSF–induced osteocla...
T cells from OVX mice fail to increase RANKL- and M-CSF–induced osteoclast differentiation of monocytes lacking the p55 TNF-α receptor. Mean (± SEM) number of osteoclasts from three independent experiments (n = 6 wells per group). BMMs were purified from C57BL/6 mice lacking either TNF-α receptor 1 (p55–/–) or TNF-α receptor II (p75–/–) and WT controls of the same genetic background and cocultured with T cells derived from OVX or estrogen-replete WT mice in the presence of optimal concentrations of RANKL and M-CSF. AP < 0.05 compared with all groups.