期刊
NATURE MEDICINE
卷 15, 期 6, 页码 682-U120出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.1954
关键词
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资金
- US National Institute of Dental and Craniofacial Research [DE17684, DE019412, DE1016513, DE13848, DE018890]
- US National Institute of Diabetes and Kidney Disease [DK053904]
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 kappa B kinase (IKK)-nuclear factor-kappa B (NF-kappa 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-kappa B in differentiated osteoblasts maintains bone formation, thereby preventing osteoporotic bone loss induced by ovariectomy in adult mice. Inhibition of IKK-NF-kappa 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-kappa B may help to promote bone formation in the treatment of osteoporosis and other bone diseases.
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