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

S Cenci, MN Weitzmann, C Roggia… - The Journal of …, 2000 - Am Soc Clin Investig
S Cenci, MN Weitzmann, C Roggia, N Namba, D Novack, J Woodring, R Pacifici
The Journal of clinical investigation, 2000Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation