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

  • Published online on: April 1, 2008     https://doi.org/10.3892/ijmm.21.4.521
  • Pages: 521-525
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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.

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April 2008
Volume 21 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Strait K, Li Y, Dillehay DL and Weitzmann MN: Suppression of NF-κB activation blocks osteoclastic bone resorption during estrogen deficiency. Int J Mol Med 21: 521-525, 2008
APA
Strait, K., Li, Y., Dillehay, D.L., & Weitzmann, M.N. (2008). Suppression of NF-κB activation blocks osteoclastic bone resorption during estrogen deficiency. International Journal of Molecular Medicine, 21, 521-525. https://doi.org/10.3892/ijmm.21.4.521
MLA
Strait, K., Li, Y., Dillehay, D. L., Weitzmann, M. N."Suppression of NF-κB activation blocks osteoclastic bone resorption during estrogen deficiency". International Journal of Molecular Medicine 21.4 (2008): 521-525.
Chicago
Strait, K., Li, Y., Dillehay, D. L., Weitzmann, M. N."Suppression of NF-κB activation blocks osteoclastic bone resorption during estrogen deficiency". International Journal of Molecular Medicine 21, no. 4 (2008): 521-525. https://doi.org/10.3892/ijmm.21.4.521