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Review
. 2010 Oct;6(10):607-11.
doi: 10.1038/nrrheum.2010.133. Epub 2010 Aug 10.

VSports最新版本 - Novel functions for NFκB: inhibition of bone formation

Susan A Krum  1 , Jia Chang, Gustavo Miranda-Carboni, Cun-Yu Wang
Affiliations
Review

Novel functions for NFκB: inhibition of bone formation (V体育平台登录)

Susan A Krum et al. Nat Rev Rheumatol. 2010 Oct.

V体育2025版 - Abstract

NFκB is a family of transcription factors involved in immunity and the normal functioning of many tissues VSports手机版. It has been well studied in osteoclasts, and new data indicate an important role for NFκB in the negative regulation of bone formation. In this article, we discuss how NFκB activation affects osteoblast function and bone formation. In particular, we describe how reduced NFκB activity in osteoblasts results in an increase in bone formation via enhanced c-Jun N-terminal kinase (JNK) activity, which regulates FOSL1 (also known as Fra1) expression. Furthermore, we discuss how estrogen and NFκB crosstalk in osteoblasts acts to oppositely regulate bone formation. Future NFκB-targeting treatments for osteoporosis, rheumatoid arthritis and other inflammatory bone diseases could lead to increased bone formation concurrent with decreased bone resorption. .

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Conflict of interest statement

Competing interests

The authors declare no competing interests.

Figures

Figure 1
Figure 1
NFκB signaling in osteoblasts. Signaling induced by cytokines, such as TNF, leads to activation of IKK, which releases NFκB from IκB. Activation of NFκB inhibits JNK activity via an unknown mechanism. Inhibition of NFκB leads to enhanced JNK activation and the upregulation of Fra1, which in turn leads to the transcription of MGP and other osteoblast proteins involved in bone formation. Abbreviations: IκB, inhibitor of κB; IKK, IκB kinase; JNK, c-Jun N-terminal kinase; MGP, matrix Gla protein; TF, transcription factor; TNF, tumor necrosis factor; TRAF, TNF receptor-associated factor.
Figure 2
Figure 2
Estrogen signaling inhibits NFκB signaling. a | NFκB signaling inhibits osteoblast differentiation and mineralization while increasing transcription of proinflammatory cytokines. b | E2 signaling inhibits NFκB signaling through several possible mechanisms. (1) ER-α might modulate IKK activity. (2) ER-α prevents IκB degradation, preventing NFκB activation. (3) Estrogen-induced ER-α might sequester coactivators (such as TIF2, p300 or CREBBP) away from NFκB. (4) ER-α has been shown to associate with NFκB, preventing NFκB binding to DNA and inhibiting transcription of cytokines. As a result, osteoblast differentiation and mineralization is increased. Abbreviations: CoA, coactivator; ER-α, estrogen receptor α; IκB, inhibitor of κB; IKK, I κB kinase; TNF, tumor necrosis factor.
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References

    1. Ghosh S, Karin M. Missing pieces in the NF-κB puzzle. Cell. 2002;109 (Suppl):S81–S96. - PubMed
    1. Granic I, Dolga AM, Nijholt IM, van Dijk G, Eisel UL. Inflammation and NF-κB in Alzheimer’s disease and diabetes. J Alzheimers Dis. 2009;16:809–821. - PubMed
    1. Geusens P. Emerging treatments for postmenopausal osteoporosis—focus on denosumab. Clin Interv Aging. 2009;4:241–250. - V体育平台登录 - PMC - PubMed
    1. Jimi E, Ghosh S. Role of nuclear factor-κB in the immune system and bone. Immunol Rev. 2005;208:80–87. - PubMed
    1. Lee ZH, Kim HH. Signal transduction by receptor activator of nuclear factor kappa B in osteoclasts. Biochem Biophys Res Commun. 2003;305:211–214. - PubMed

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