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 κB (NF-κB) 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 κB kinase γ (IKK-γ) that prevents activation of NF-κB] 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-κB 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-κB. Nat. Med. 15, 682–689 (2009). [PubMed]