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

Research output: Contribution to journalArticlepeer-review

490 Scopus citations

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.

Original languageEnglish
Pages (from-to)1229-1237
Number of pages9
JournalJournal of Clinical Investigation
Volume106
Issue number10
DOIs
StatePublished - 2000

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