Neutralization of interleukin-11 activity decreases osteoclast formation and increases cancellous bone volume in ovariectomized mice.
The issue of whether interleukin-11 (IL-11) contributes to bone loss during states of estrogen deficiency has not been previously determined. We therefore randomized ovariectomized (OVX) mice to once daily interperitoneal injections of either sheep anti-murine IL-11 Ab or normal sheep IgG (NSIgG) for 21 days, and then determined the effects on bone using bone histomorphometry. Here we report that treatment of OVX mice with anti-IL-11 Ab significantly increases both trabecular width and cancellous bone volume. Osteoblast activity, as measured by the percentage of trabecular surface covered by osteoid and rates of bone formation, were also significantly increased following treatment with anti-IL-11 Ab. In contrast, treatment of OVX mice with anti-IL-11 Ab significantly decreased both osteoclast number and activity. Ex-vivo assays of osteoclast formation and activity confirmed the histomorphometric data. Thus, bone marrow cells isolated from anti-IL-11 Ab treated OVX mice formed fewer osteoclasts and resorbed less bone in culture than did marrow cells isolated from either untreated or NSIgG-treated OVX mice. Based on these results we conclude that IL-11 contributes to the bone loss which is observed during states of estrogen deficiency.
Shaughnessy
Stephen G
SG
Department of Pathology and Molecular Medicine, McMaster University and the Hamilton Civic Hospitals Research Centre, Hamilton, Ontario, Canada. sshaughnessy@thrombosis.hhscr.org
Walton
Kimberly J
KJ
Deschamps
Paula
P
Butcher
Martin
M
Beaudin
Suzanne M
SM
D000818:Animals; D016723:Bone Remodeling / Q000276:immunology* / Q000502:physiology; D004967:Estrogens / Q000172:deficiency; D005260:Female; D066298:In Vitro Techniques; D017370:Interleukin-11 / Q000037:antagonists & inhibitors* / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D009500:Neutralization Tests; D010010:Osteoclasts / Q000166:cytology* / Q000276:immunology*; D010052:Ovariectomy; D012756:Sheep
D004967:Estrogens; D017370:Interleukin-11