Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 16 June 2009
Vol. 2, Issue 75, p. ec198
[DOI: 10.1126/scisignal.275ec198]

EDITORS' CHOICE

Osteoblast Function Redressing the Balance

John F. Foley

Science Signaling, AAAS, Washington, DC 20005, USA

The maintenance of bone density in adult animals depends on the balance between the activities of osteoblasts, which form bone, and osteoclasts, which resorb bone. In osteoporosis, the formation of new bone cannot match the pace at which bone is resorbed, which results in a net loss of bone density. Although the role of nuclear factor {kappa}B (NF-{kappa}B) in osteoclast function is well described, its possible role in osteoblast function is unclear. Chang et al. generated transgenic mice that expressed IKK-DN [a dominant-negative (DN) form of inhibitor of {kappa}B kinase {gamma} (IKK-{gamma}) that prevents activation of NF-{kappa}B] under the control of a promoter that is active in differentiated osteoblasts. Trabecular bone density and volume were greater in IKK-DN mice than in wild-type (WT) mice at the ages of 2 and 4 weeks, although there was no difference in osteoblast number. Real-time reverse transcription polymerase chain reaction assays showed that genes necessary for bone formation were more highly expressed in IKK-DN mice than in WT mice. Osteoclast number and function were similar in both groups of mice. The AP-1 family member Fra-1, which is essential for bone formation, was more abundant in IKK-DN mice than in WT mice, and knockdown of Fra-1 reduced the bone density of IKK-DN mice. Removal of the ovaries of mice generates a model of bone loss that mimics postmenopausal osteoporosis. Whereas ovariectomized WT mice suffered the expected losses in trabecular bone density and volume, ovariectomized IKK-DN mice suffered from far less bone loss. The authors thus suggest inhibition of NF-{kappa}B activity as a therapy against the loss of bone density caused by postmenopausal osteoporosis.

J. Chang, Z. Wang, E. Tang, Z. Fan, L. McCauley, R. Franceschi, K. Guan, P. H. Krebsbach, C.-Y. Wang, Inhibition of osteoblastic bone formation by nuclear factor-{kappa}B. Nat. Med. 15, 682–689 (2009). [PubMed]

Citation: J. F. Foley, Redressing the Balance. Sci. Signal. 2, ec198 (2009).



To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882