Abstract
The osteoclast (OC) is the resorptive cell of the skeleton responsible for both normal homeostasis and pathological bone loss. NF-κB is a critical signal for OC differentiation downstream of RANKL, and its global disruption protects mice from pathological bone loss. Differently from other TNF family members, RANKL activates both the classical NF-κB pathway, activating both p65 and cRel, and the alternative pathway, inducing expression and activation of RelB. In order to determine whether the classical and alternative NF-κB pathways have distinct roles in OC differentiation, we examined mice lacking p65, RelB, or cRel.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Vaira S, Johnson T, Hirbe AC, Alhawagri M, Anwisye I, Sammut B, O’Neal J, Zou W, Weilbaecher KN, Faccio R et al (2008) RelB is the NF-kB subunit downstream of NIK responsible for osteoclast differentiation. Proc Natl Acad Sci U S A 105:3897–3902
Jimi E, Akiyama S, Tsurukai T, Okahashi N, Kobayashi K, Udagawa N, Nishihara T, Takahashi N, Suda T (1999) Osteoclast differentiation factor acts as a multifunctional regulator in murine osteoclast differentiation and function. J Immunol 163:434–442
Beg AA, Sha WC, Bronson RT, Ghosh S, Baltimore D (1995) Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kB. Nature 376:167–170
Vaira S, Alhawagri M, Anwisye I, Kitaura H, Faccio R, Novack DV (2008) RelA/p65 promotes osteoclast differentiation by blocking a RANKL-induced apoptotic JNK pathway in mice. J Clin Invest 118:2088–2097
De Smaele E, Zazzeroni F, Papa S, Nguyen DU, Jin R, Jones J, Cong R, Franzoso G (2001) Induction of gadd45b by NF-kB downregulates pro-apoptotic JNK signalling. Nature 414:308–313
Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M (2005) Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 120:649–661
Papa S, Zazzeroni F, Pham CG, Bubici C, Franzoso G (2004) Linking JNK signaling to NF-kB: a key to survival. J Cell Sci 117:5197–5208
Novack DV, Yin L, Hagen-Stapleton A, Schreiber RD, Goeddel DV, Ross FP, Teitelbaum SL (2003) The IkB function of NF-kB2 p100 controls stimulated osteoclastogenesis. J Exp Med 198:771–781
Aya K, Alhawagri M, Hagen-Stapleton A, Kitaura H, Kanagawa O, Novack DV (2005) NF-(kappa)B-inducing kinase controls lymphocyte and osteoclast activities in inflammatory arthritis. J Clin Invest 115:1848–1854
Iotsova V, Caamano J, Loy J, Yang Y, Lewin A, Bravo R (1997) Osteopetrosis in mice lacking NF-kappaB1 and NF-kappaB2. Nature Med 3:1285–1289
Franzoso G, Carlson L, Xing L, Poljak L, Shores EW, Brown KD, Leonardi A, Tran T, Boyce BF, Siebenlist U (1997) Requirement for NF-kappaB in osteoclast and B-cell development. Genes Dev 11:3482–3496
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this paper
Cite this paper
Novack, D.V. (2011). Unique Personalities Within the NF-κB Family: Distinct Functions for p65 and RelB in the Osteoclast. In: Wallach, D., Kovalenko, A., Feldmann, M. (eds) Advances in TNF Family Research. Advances in Experimental Medicine and Biology, vol 691. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6612-4_17
Download citation
DOI: https://doi.org/10.1007/978-1-4419-6612-4_17
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-6611-7
Online ISBN: 978-1-4419-6612-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)