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The Functional Block of TNF but Not of IL‐6 Prevents Bone Loss in Ovariectomized Mice
Author(s) -
Kimble Robert B.,
Bain Steve,
Pacifici Roberto
Publication year - 1997
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1997.12.6.935
Subject(s) - bone resorption , endocrinology , osteoclast , ovariectomized rat , medicine , cytokine , estrogen , tumor necrosis factor alpha , bone remodeling , osteoporosis , resorption , receptor
Considerable evidence supports the hypothesis that estrogen prevents bone loss by blocking the bone marrow cell production of pro‐osteoclastogenic cytokines. However, controversy remains on the role of candidate factors, such as tumor necrosis factor (TNF) and interleukin‐6 (IL‐6). To investigate the contribution of these cytokines to the pathogenesis of ovariectomy (OVX)‐induced bone loss, OVX mice were treated with either TNF binding protein (TNFbp), an inhibitor of TNF, the anti–(IL‐6) antibody (Ab) 20F3, or estrogen for the first 2 weeks after surgery. OVX caused a rapid decrease in trabecular bone volume (TBV) and an increase in in vivo bone resorption, as assessed by bone histomorphometry. Treatment with TNFbp completely prevented bone loss and the increase in both osteoclast formation and bone resorption induced by OVX, but had no effects in sham‐operated controls. In contrast, treatment with anti–IL‐6 antibody failed to prevent bone loss, and the increase in bone resorption and osteoclastogenesis induced by OVX. These data demonstrate that in nongenetically manipulated mice, the estrogen‐regulated cytokine that plays a central role in the mechanism by which estrogen deficiency causes bone loss is not IL‐6, but rather TNF.