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Unique Personalities Within the NF-κB Family: Distinct Functions for p65 and RelB in the Osteoclast

  • Deborah Veis Novack
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 691)

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.

Keywords

Resorptive Cell Form Actin Ring Radiation Chimera Murine Tumor Cell Line Inflammatory Osteolysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    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 105:3897–3902CrossRefPubMedGoogle Scholar
  2. 2.
    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 163:434–442PubMedGoogle Scholar
  3. 3.
    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 376:167–170CrossRefPubMedGoogle Scholar
  4. 4.
    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 118:2088–2097PubMedGoogle Scholar
  5. 5.
    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 414:308–313CrossRefPubMedGoogle Scholar
  6. 6.
    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 120:649–661CrossRefPubMedGoogle Scholar
  7. 7.
    Papa S, Zazzeroni F, Pham CG, Bubici C, Franzoso G (2004) Linking JNK signaling to NF-kB: a key to survival. J Cell Sci 117:5197–5208CrossRefPubMedGoogle Scholar
  8. 8.
    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 198:771–781CrossRefPubMedGoogle Scholar
  9. 9.
    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 115:1848–1854CrossRefPubMedGoogle Scholar
  10. 10.
    Iotsova V, Caamano J, Loy J, Yang Y, Lewin A, Bravo R (1997) Osteopetrosis in mice lacking NF-kappaB1 and NF-kappaB2. Nature Med 3:1285–1289CrossRefPubMedGoogle Scholar
  11. 11.
    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 11:3482–3496CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Division of Bone and Mineral Diseases, Departments of Medicine and PathologyWashington University School of MedicineSt. LouisUSA

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