Original Article

You have full text access to this OnlineOpen article

The pivotal role of the alternative NF-κB pathway in maintenance of basal bone homeostasis and osteoclastogenesis†

  1. Niroshani S Soysa1,
  2. Neil Alles1,2,
  3. Debra Weih3,
  4. Agnes Lovas3,
  5. Anower Hussain Mian1,
  6. Hitoyata Shimokawa1,
  7. Hisataka Yasuda4,
  8. Falk Weih3,
  9. Eijiro Jimi5,
  10. Keiichi Ohya1,
  11. Kazuhiro Aoki1,*

Article first published online: 14 DEC 2009

DOI: 10.1359/jbmr.091030

Issue

Journal of Bone and Mineral Research

Journal of Bone and Mineral Research

Volume 25, Issue 4, pages 809–818, April 2010

Additional Information

How to Cite

Soysa, N. S., Alles, N., Weih, D., Lovas, A., Mian, A. H., Shimokawa, H., Yasuda, H., Weih, F., Jimi, E., Ohya, K. and Aoki, K. (2010), The pivotal role of the alternative NF-κB pathway in maintenance of basal bone homeostasis and osteoclastogenesis. J Bone Miner Res, 25: 809–818. doi: 10.1359/jbmr.091030

Author Information

  1. 1

    Section of Pharmacology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan

  2. 2

    Global Center of Excellence Program (G-COE), Tokyo Medical and Dental University, Tokyo, Japan

  3. 3

    Leibniz Institute for Age Research, Fritz Lipmann Institute (FLI), Research Group Immunology, Jena, Germany

  4. 4

    Nagahama Institute for Biochemical Science, Oriental Yeast Co., Ltd, Shiga, Japan

  5. 5

    Division of Molecular Biochemistry, Department of Biosciences, Kyushu Dental College, Kyushu, Japan

*Section of Pharmacology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.

  1. †

    The first two authors contributed equally to this work.

Publication History

  1. Issue published online: 9 APR 2010
  2. Article first published online: 14 DEC 2009
  3. Accepted manuscript online: 27 JAN 2010 12:00AM EST
  4. Manuscript Accepted: 15 OCT 2009
  5. Manuscript Revised: 31 AUG 2009
  6. Manuscript Received: 27 FEB 2009

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (591K)

References

  • 1
    Iotsova V, Caamano J, Loy J, Yang Y, Lewin A, Bravo R. Osteopetrosis in mice lacking NF-κB1 and NF-κB2. Nat Med. 1997; 3: 1285–1289.
  • 2
    Franzoso G, Carlson L, Xing L, et al. Requirement for NF-κB in osteoclast and B-cell development. Genes Dev. 1997; 11: 3482–3496.
  • 3
    Soysa NS, Alles N. NF-κB functions in osteoclasts. Biochem Biophys Res Commun. 2009; 378: 1–5.
  • 4
    Vaira S, Johnson T, Hirbe AC, et al. RelB is the NF-kB subunit downstream of NIK responsible for osteoclast differentiation. Proc Natl Acad Sci USA. 2008; 105: 3897–3902.
  • 5
    Tucker E, O'Donnell K, Fuchsberger M, et al. A novel mutation in the Nfkb2 gene generates an NF-κB2 “super repressor”. J Immunol. 2007; 179: 7514–7522.
  • 6
    Shinkura R, Kitada K, Matsuda F, et al. Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-κB-inducing kinase. Nat Genet. 1999; 22: 74–77.
  • 7
    Yin L, Wu L, Wesche H, et al. Defective lymphotoxin-b receptor-induced NF-κB transcriptional activity in NIK-deficient mice. Science. 2001; 291: 2162–2165.
  • 8
    Novack DV, Yin L, Hagen-Stapleton A, et al. The IκB function of NF-κB2 p100 controls stimulated osteoclastogenesis. J Exp Med. 2003; 198: 771–781.
  • 9
    Guo F, Tanzer S, Busslinger M, Weih F. Lack of nuclear factor-κB2/p100 causes a RelB-dependent block in early B lymphopoiesis. Blood. 2008; 112: 551–559.
  • 10
    Ishikawa H, Carrasco D, Claudio E, Ryseck RP, Bravo R. Gastric hyperplasia and increased proliferative responses of lymphocytes in mice lacking the COOH-terminal ankyrin domain of NF-κB2. J Exp Med. 1997; 186: 999–1014.
  • 11
    Alles N, Soysa NS, Hussain MD, et al. Polysaccharide nanogel delivery of a TNF-α and RANKL antagonist peptide allows systemic prevention of bone loss. Eur J Pharm Sci. 2009; 37: 83–88.
  • 12
    Saito H, Kojima T, Takahashi M, et al. A tumor necrosis factor receptor loop peptide mimic inhibits bone destruction to the same extent as anti-tumor necrosis factor monoclonal antibody in murine collagen-induced arthritis. Arthritis Rheum. 2007; 56: 1164–1174.
    Direct Link:
  • 13
    Hussain Mian A, Saito H, Alles N, Shimokawa H, Aoki K, Ohya K. Lipopolysaccharide-induced bone resorption is increased in TNF type 2 receptor-deficient mice in vivo. J Bone Miner Metab. 2008; 26: 469–477.
  • 14
    Soysa NS, Alles N, Shimokawa H, Jimi E, Aoki K, Ohya K. Inhibition of the classical NF-κB pathway prevents osteoclast bone-resorbing activity. J Bone Miner Metab. 2009; 27: 131–139.
  • 15
    Saito H, Soysa N, Alles N, Aoki K, Ohya K. Three-Dimensional Measurements of Bone Resorption Lacunae Reveal Inhibition of Osteoclast Activity by TNF-α Antagonists In vitro. Dentistry In Japan. 2006; 42: 35–37.
  • 16
    Aoki K, Saito H, Itzstein C, et al. A TNF receptor loop peptide mimic blocks RANK ligand-induced signaling, bone resorption, and bone loss. J Clin Invest. 2006; 116: 1525–1534.
  • 17
    Renard P, Ernest I, Houbion A, et al. Development of a sensitive multi-well colorimetric assay for active NF-κB. Nucleic Acids Res. 2001; 29: E21.
  • 18
    Yamada T, Mitani T, Yorita K, et al. Abnormal immune function of hemopoietic cells from alymphoplasia (aly) mice, a natural strain with mutant NF-κB-inducing kinase. J Immunol. 2000; 165: 804–812.
  • 19
    Xiao G, Harhaj EW, Sun SC. NF-κB-inducing kinase regulates the processing of NF-κB2 p100. Mol Cell. 2001; 7: 401–409.
  • 20
    Naumann M, Nieters A, Hatada EN, Scheidereit C. NF-κB precursor p100 inhibits nuclear translocation and DNA binding of NF-κB/rel-factors. Oncogene. 1993; 8: 2275–2281.
  • 21
    Scheinman RI, Beg AA, Baldwin AS Jr. NF-κB p100 (Lyt-10) is a component of H2TF1 and can function as an IκB-like molecule. Mol Cell Biol. 1993; 13: 6089–6101.
  • 22
    Sun SC, Ganchi PA, Beraud C, Ballard DW, Greene WC. Autoregulation of the NF-κB transactivator RelA (p65) by multiple cytoplasmic inhibitors containing ankyrin motifs. Proc Natl Acad Sci USA. 1994; 91: 1346–1350.
View Full Article (HTML) Get PDF (591K)