Skip to main content

Regulation of Osteoclast Apoptosis by Bcl-2 Family Protein Bim and Caspase-3

  • Conference paper
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 658))

Abstract

Apopotosis of osteoclasts is regulated by the Bcl-2 family protein Bim. Bim is degraded in the course of osteoclast apoptosis, which is regulated by Caspase-3. Osteoclasts generated from caspase-3 –/– mice exhibited a shorter life span and a higher bone-resorbing activity than those generated from normal littermates. These results suggest the important role of Caspase-3-Bim axis in regulating both apoptosis and activation of osteoclasts.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Akiyama, T., Bouillet, P., Miyazaki, T., Kadono, Y., Chikuda, H., Chung, U. I. et al. (2003). Regulation of osteoclast apoptosis by ubiquitylation of proapoptotic BH3-only Bcl-2 family member Bim. Embo J 22:6653–6664.

    Article  CAS  PubMed  Google Scholar 

  2. Bouillet, P., Metcalf, D., Huang, D. C., Tarlinton, D. M., Kay, T. W., Kontgen, F. et al. (1999). Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 286:1735–1738.

    Article  Google Scholar 

  3. Bouillet, P., Purton, J. F., Godfrey, D. I., Zhang, L. C., Coultas, L., Puthalakath, H. et al. (2002). -only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes. Nature 415:922–926.

    Article  CAS  PubMed  Google Scholar 

  4. Gilley, J., Coffer, P. J., & Ham, J. (2003). FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons. J Cell Biol 162:613–622.

    Article  CAS  PubMed  Google Scholar 

  5. Huang, D. C., & Strasser, A. (2000). BH3-Only proteins-essential initiators of apoptotic cell death. Cell 103:839–842.

    Article  CAS  PubMed  Google Scholar 

  6. Kerr, J. F., Wyllie, A. H., & Currie, A. R. (1972). Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257.

    CAS  PubMed  Google Scholar 

  7. Ley, R., Balmanno, K., Hadfield, K., Weston, C. R., & Cook, S. J. (2003). Activation of the ERK1/2 signalling pathway promotes phosphorylation and proteasome-dependent degradation of the BH3-only protein Bim. J Biol Chem 278:18811–18816.

    Article  CAS  PubMed  Google Scholar 

  8. Meller, R., Cameron, J. A., Torrey, D. J., Clayton, C. E., Ordonez, A. N., Henshall, D. C. et al. (2006). Rapid degradation of Bim by the ubiquitin-proteasome pathway mediates short-term ischemic tolerance in cultured neurons. J Biol Chem 281:7429–7436.

    Article  CAS  PubMed  Google Scholar 

  9. Miura, M., Chen, X. D., Allen, M. R., Bi, Y., Gronthos, S., Seo, B. M. et al. (2004). A crucial role of caspase-3 in osteogenic differentiation of bone marrow stromal stem cells. J Clin Invest 114:1704–1713.

    CAS  PubMed  Google Scholar 

  10. Miyazaki, T., Katagiri, H., Kanegae, Y., Takayanagi, H., Sawada, Y., Yamamoto, A. et al (2000). Reciprocal role of ERK and NF-kappaB pathways in survival and activation of osteoclasts. J Cell Biol 148:333–342.

    Article  CAS  PubMed  Google Scholar 

  11. Morishita, H., Makishima, T., Kaneko, C., Lee, Y. S., Segil, N., Takahashi, K. et al. (2001). Deafness due to degeneration of cochlear neurons in caspase-3-deficient mice. Biochem Biophys Res Commun 284:142–149.

    Article  CAS  PubMed  Google Scholar 

  12. O‘Connor, L., Strasser, A., O‘Reilly, L. A., Hausmann, G., Admas, J. M., Cory, S. et al. (1998). Bim: a novel member of the Bcl-2 family that promotes apoptosis. Embo J 17: 384–395.

    Article  PubMed  Google Scholar 

  13. Opferman, J. T., & Korsmeyer, S. J. (2003). Apoptosis in the development and maintenance of the immune system. Nat Immunol 4:410–415.

    Article  CAS  PubMed  Google Scholar 

  14. Putcha, G. V., Moulder, K. L., Golden, J. P., Bouillet, P., Adams, J. A., Strasser, A. et al. (2001). Induction of BIM, a proapoptotic BH3-only BCL-2 family member, is critical for neuronal apoptosis. Neuron 29:615–628.

    Article  CAS  PubMed  Google Scholar 

  15. Siegel, R. M. (2006). Caspases at the crossroads of immune-cell life and death. Nat Rev Immunol 6:308–317.

    Article  CAS  PubMed  Google Scholar 

  16. Tanaka, S. (2007). Signaling axis in osteoclast biology and therapeutic targeting in the RANKL/RANK/OPG system. Am J Nephrol 27:466–478.

    Article  PubMed  Google Scholar 

  17. Tanaka, S., Nakamura, I., Inoue, J., Oda, H., & Nakamura, K. (2003). Signal transduction pathways regulating osteoclast differentiation and function. J Bone Miner Metab 21:123–133.

    Article  PubMed  Google Scholar 

  18. Tanaka, S., Nakamura, K., Takahasi, N., & Suda, T. (2005). Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system. Immunol Rev 208:30–49.

    Article  CAS  PubMed  Google Scholar 

  19. Wakeyama, H., Akiyama, T., Kadono, Y., Nakamura, M., Oshima, Y., Nakamura, K. et al. (2007a). Posttranslational regulation of Bim by caspase-3. Ann N Y Acad Sci 1116:271–280.

    Article  CAS  PubMed  Google Scholar 

  20. Wakeyama, H., Akiyama, T., Takahashi, K., Amano, H., Kadono, Y., Nakamura, M. et al. (2007b). Negative feedback loop in the Bim-caspase-3 axis regulating apoptosis and activity of osteoclasts. J Bone Miner Res 22:1631–1639.

    Article  CAS  PubMed  Google Scholar 

  21. Wiggins, C. M., Band, H., & Cook, S. J. (2007). c-Cbl is not required for ERK1/2-dependent degradation of BimEL. Cell Signal 19:2605–2611.

    Article  CAS  PubMed  Google Scholar 

  22. Wyllie, A. H., Kerr, J. F., & Currie, A. R. (1980). Cell death: the significance of apoptosis. Int Rev Cytol 68:251–306.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Health Science research grants from the Ministry of Health, Labor, and Welfare of Japan to S.T.

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media, LLC

About this paper

Cite this paper

Tanaka, S. et al. (2009). Regulation of Osteoclast Apoptosis by Bcl-2 Family Protein Bim and Caspase-3. In: Choi, Y. (eds) Osteoimmunology. Advances in Experimental Medicine and Biology, vol 658. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-1050-9_12

Download citation

Publish with us

Policies and ethics