Inhibition of Osteoblastic Bone Formation by Nuclear Factor-kappaB

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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 kappaB kinase (IKK)-nuclear factor-kappaB (NF-kappaB) in differentiated osteoblasts substantially increases trabecular bone mass and bone mineral density without affecting osteoclast activities in young mice. Moreover, inhibition of IKK-NF-kappaB in differentiated osteoblasts maintains bone formation, thereby preventing osteoporotic bone loss induced by ovariectomy in adult mice. Inhibition of IKK-NF-kappaB 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-kappaB may help to promote bone formation in the treatment of osteoporosis and other bone diseases.

Comment: The role of immune driven inflammation in the management of bone health has been discussed for some time. The application of natural inhibitors of NFkB by the ingestion of food concentrates including, Vit D, Curcuminoids, Green tea and others represent a potential method of reducing rate of bone loss amongst many other health derived benefits links to immune tolerance.

Chang J, et al. Inhibition of osteoblastic bone formation by nuclear factor-kappaB. Nature Medicine 15, 682 – 689 (2009) Published online: 17 May 2009 | doi:10.1038/nm.1954 View Abstract

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