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.
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References
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.
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.
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.
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.
Huang, D. C., & Strasser, A. (2000). BH3-Only proteins-essential initiators of apoptotic cell death. Cell 103:839–842.
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.
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.
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.
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.
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.
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.
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.
Opferman, J. T., & Korsmeyer, S. J. (2003). Apoptosis in the development and maintenance of the immune system. Nat Immunol 4:410–415.
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.
Siegel, R. M. (2006). Caspases at the crossroads of immune-cell life and death. Nat Rev Immunol 6:308–317.
Tanaka, S. (2007). Signaling axis in osteoclast biology and therapeutic targeting in the RANKL/RANK/OPG system. Am J Nephrol 27:466–478.
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.
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.
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.
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.
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.
Wyllie, A. H., Kerr, J. F., & Currie, A. R. (1980). Cell death: the significance of apoptosis. Int Rev Cytol 68:251–306.
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.
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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
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DOI: https://doi.org/10.1007/978-1-4419-1050-9_12
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