TY - JOUR
T1 - Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-α
AU - Cenci, Simone
AU - Weitzmann, M. Neale
AU - Roggia, Cristiana
AU - Namba, Noriyuki
AU - Novack, Deborah
AU - Woodring, Jessica
AU - Pacifici, Roberto
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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M3 - Article
C2 - 11086024
AN - SCOPUS:0033708837
VL - 106
SP - 1229
EP - 1237
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 10
ER -