Suppression of NF-κB activation blocks osteoclastic bone resorption during estrogen deficiency

Strait,Karen; Li,Yan; Dillehay,Dirck L.; Weitzmann,M. Neale

doi:10.3892/ijmm.21.4.521

April 2008 Volume 21 Issue 4

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April 2008 Volume 21 Issue 4

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Article

Suppression of NF-κB activation blocks osteoclastic bone resorption during estrogen deficiency

Authors:
- Karen Strait
- Yan Li
- Dirck L. Dillehay
- M. Neale Weitzmann
View Affiliations / Copyright

Affiliations: Division of Animal Resources, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
Pages: 521-525
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Published online on: April 1, 2008

https://doi.org/10.3892/ijmm.21.4.521
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Abstract

Postmenopausal osteoporosis stems from an imbalance in osteoclastic bone resorption with respect to osteoblastic bone formation, a consequence of estrogen deficiency. The nuclear factor-κB (NF-κB) signal transduction pathway is critical for osteoclast formation and resorption, and suppression of NF-κB activation has been shown to block bone resorption in vitro, and to ameliorate inflammatory bone loss in vivo. The use of NF-κB antagonists to blunt the bone loss associated with estrogen deficiency however, has not been previously reported. In this study, we investigated whether pharmacological suppression of NF-κB signaling protects mice against ovariectomy (ovx)-induced bone loss. Ovx mice were treated with the potent NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) for 4 weeks and bone mineral density (BMD) and indices of bone structure quantitated by dual-energy X-ray absorptiometry (DXA), and μ-computed tomography (μCT). In vivo indices of bone resorption were quantitated in mouse serum using the biochemical marker C-terminal telopeptide of collagen (CTx). Our data revealed that NF-κB suppression significantly prevented ovx-induced bone destruction by preventing the increase in ovx-induced osteoclastic bone resorption. Our data suggest that NF-κB inhibitors may represent novel anticatabolic therapeutic agents for the amelioration of postmenopausal bone loss.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Suppression of NF-κB activation blocks osteoclastic bone resorption during estrogen deficiency

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Abstract

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