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

Estrogen deficiency induces bone loss by upregulating osteoclastogenesis by mechanisms not completely defined. We found that ovariectomy-enhanced T-ce ll production of TNF-alpha, which, acting through the TNF-a receptor p55, a ugments macrophage colony-stimulating factor-induced (hl-CSF-induced) and R ANKL-induced osteoclastogenesis. Ovariectomy failed to induce bone loss, st imulate bone resorption, or increase M-CSF- and RANKL-dependent osteoclasto genesis in T-cell deficient mice, establishing T cells as essential mediato rs of the bone-wasting effects of estrogen deficiency in vivo. These findin gs demonstrate that the ability of estrogen to target T cells, suppressing their production of TNF-alpha, is a key mechanism by which estrogen prevent s osteoclastic bone resorption and bone loss.