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Novel functions for NFκB: inhibition of bone formation

Nature Reviews Rheumatology volume 6, pages 607–611 (2010)Cite this article

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Abstract

NFκB is a family of transcription factors involved in immunity and the normal functioning of many tissues. 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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Figure 1: NFκB signaling in osteoblasts.
Figure 2: Estrogen signaling inhibits NFκB signaling.

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Acknowledgements

This work was supported by a K12 BIRCWH grant to S. A. Krum from the NIH/ORWH (HD001400-08) and by DE17684, DE019412, DE016513, DE13848 from National Institute of Craniofacial and Dental Research and CA100849 from National Cancer Institute to C.-Y. Wang. The authors would like to thank Benny Gee, UCLA Life Sciences, for help with the figures.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, UCLA Orthopaedic Hospital, David Geffen School of Medicine at UCLA, 615 Charles E Young Drive South, OHRC 410, Los Angeles, 90095, CA, USA

    Susan A. Krum

  2. Division of Oral Biology and Medicine, Laboratory of Molecular Signaling, UCLA School of Dentistry, Box 951668, 33-030A CHS, 10833 Le Conte Avenue, Los Angeles, 90095, CA, USA

    Jia Chang & Cun-Yu Wang

  3. Department of Obstetrics and Gynecology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, 27-139 CHS, 10833 Le Conte Avenue, Los Angeles, 90095, CA, USA

    Gustavo Miranda-Carboni

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Contributions

S. A. Krum, J. Chang and C.-Y. Wang researched data for the article. S. Krum, G. Miranda-Carboni and C.-Y. Wang made substantial contributions to the discussion of the article's content. S. A. Krum, G. Miranda-Carboni and C.-Y. Wang were involved in writing the article. All the authors took part in review/editing of the manuscript before submission.

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Correspondence to Cun-Yu Wang.

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Krum, S., Chang, J., Miranda-Carboni, G. et al. Novel functions for NFκB: inhibition of bone formation. Nat Rev Rheumatol 6, 607–611 (2010). https://doi.org/10.1038/nrrheum.2010.133

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