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Neutralization of interleukin-11 activity decreases osteoclast formation and increases cancellous bone volume in
Stephen G Shaughnessy1, Kimberly J Walton, Paula Deschamps
1Department of Pathology and Molecular Medicine, McMaster University and the Hamilton Civic Hospitals Research Centre, Hamilton, Ontario, Canada. sshaughnessy@thrombosis.hhscr.org
Abstract:
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.
Insights
Interleukin-11 (IL-11) drives bone loss in estrogen deficiency. Blocking IL-11 with an antibody in ovariectomized mice increased bone volume and formation while decreasing bone resorption.
Area of Science:
- Endocrinology
- Bone Biology
- Immunology
Background:
- Estrogen deficiency, common in menopause, leads to significant bone loss.
- The role of interleukin-11 (IL-11) in this process remains unclear.
- Understanding IL-11's contribution is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the effect of blocking interleukin-11 (IL-11) on bone loss in a mouse model of estrogen deficiency.
- To determine if IL-11 inhibition can mitigate ovariectomy-induced bone loss.
Main Methods:
- Ovariectomized (OVX) mice were treated with anti-IL-11 antibody or control IgG.
- Bone histomorphometry was used to assess bone parameters and cellular activity.
- Ex-vivo assays evaluated osteoclast formation and bone resorption.
Main Results:
- Anti-IL-11 treatment significantly increased trabecular width and cancellous bone volume in OVX mice.
- Osteoblast activity and bone formation rates were enhanced by anti-IL-11 blockade.
- Osteoclast number and activity were significantly reduced, with decreased ex-vivo osteoclastogenesis and bone resorption.
Conclusions:
- Interleukin-11 (IL-11) plays a significant role in mediating bone loss associated with estrogen deficiency.
- Inhibition of IL-11 presents a potential therapeutic strategy to prevent or treat bone loss in postmenopausal women.