The functional block of TNF but not of IL-6 prevents bone loss in ovariectomized mice

R B Kimble, Robert B. Kimble, S Bain, Steve Bain, Roberto Pacifici, R Pacifici
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 1997 · vol. 12(6) , pp. 935–941 · doi:10.1359/jbmr.1997.12.6.935 · PMID:9169353 · W2062028959
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In ovariectomized mice, blocking TNF prevented estrogen deficiency-induced bone loss and increased osteoclastogenesis, whereas inhibiting IL-6 failed to prevent these changes.

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Abstract

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.

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MeSH descriptors

Bone Resorption Interleukin-6 Inhibitors Tumor Necrosis Factor-alpha Animals Antibodies Antibodies Bone Resorption Bone Resorption Estrogens Estrogens Estrogens Estrogens Female Interleukin-6 Interleukin-6 Mice Mice, Inbred C3H Ovariectomy Ovary Ovary

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