Article abstract
Nature Medicine 15, 682 - 689 (2009)
Published online: 17 May 2009 | doi:10.1038/nm.1954
Inhibition of osteoblastic bone formation by nuclear factor-
B
Jia Chang1, Zhuo Wang2, Eric Tang1, Zhipeng Fan1, Laurie McCauley3,4, Renny Franceschi3, Kunliang Guan5, Paul H Krebsbach2 & Cun-Yu Wang1
Abstract
An imbalance in bone formation relative to bone resorption results in the net bone loss that occurs in osteoporosis and inflammatory bone diseases. Although it is well known how bone resorption is stimulated, the molecular mechanisms that mediate impaired bone formation are poorly understood. Here we show that the time- and stage-specific inhibition of endogenous inhibitor of 
B kinase (IKK)–nuclear factor-B (NF-B) in differentiated osteoblasts substantially increases trabecular bone mass and bone mineral density without affecting osteoclast activities in young mice. Moreover, inhibition of IKK–NF-B in differentiated osteoblasts maintains bone formation, thereby preventing osteoporotic bone loss induced by ovariectomy in adult mice. Inhibition of IKK–NF-B enhances the expression of Fos-related antigen-1 (Fra-1), an essential transcription factor involved in bone matrix formation in vitro and in vivo. Taken together, our results suggest that targeting IKK–NF-B may help to promote bone formation in the treatment of osteoporosis and other bone diseases.
- Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry and Jonsson Comprehensive Cancer Center, University of California–Los Angeles, Los Angeles, California, USA.
- Department of Biologic and Materials Sciences, Ann Arbor, Michigan, USA.
- Department of Periodontics and Oral Medicine, School of Dentistry, Ann Arbor, Michigan, USA.
- Department of Pathology, School of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
- Department of Pharmacology and Comprehensive Cancer Center, University of California–San Diego, San Diego, California, USA.
Correspondence to: Cun-Yu Wang1 e-mail: cwang@dentistry.ucla.edu
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