BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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New understanding of glucocorticoid action in bone cells

  • Kim, Hyun-Ju (Skeletal Diseases Genome Research Center, Department of Medicine, Kyungpook National University School of Medicine)
  • 투고 : 2010.07.06
  • 발행 : 2010.08.31
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초록

Glucocorticoids (GCs) are useful drugs for the treatment of various diseases, but their use for prolonged periods can cause severe side effects such as osteoporosis. GCs have a direct effect on bone cells, where they can arrest bone formation, in part through the inhibition of osteoblast. On the other hand, GCs potently suppress osteoclast resorptive activity by disrupting its cytoskeleton based on the inhibition of RhoA, Rac and Vav3 in response to macrophage colony-stimulating factor. GCs also interfere with microtubule distribution and stability, which are critical for cytoskeletal organization in osteoclasts. Thus, GCs inhibit microtubule-dependent cytoskeletal organization in osteoclasts, which, in the context of bone remodeling, further dampens bone formation.

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참고문헌

  1. Manolagas, S. C. and Weinstein, R. S. (1999) New developments in the pathogenesis and treatment of steroid-induced osteoporosis. J. Bone Miner Res. 14, 1061-1066. https://doi.org/10.1359/jbmr.1999.14.7.1061
  2. Weinstein, R. S. (2001) Glucocorticoid-induced osteoporosis. Rev. Endocr. Metab. Disord. 2, 65-73. https://doi.org/10.1023/A:1010007108155
  3. Lukert, B. P. and Raisz, L. G. (1990) Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann. Intern. Med. 112, 352-364. https://doi.org/10.7326/0003-4819-112-5-352
  4. Canalis, E., Bilezikian, J. P., Angeli, A. and Giustina, A. (2004) Perspectives on glucocorticoid-induced osteoporosis. Bone 34, 593-598. https://doi.org/10.1016/j.bone.2003.11.026
  5. Luengo, M., Picado, C., Piera, C., Guanabens, N., Montserrat, J. M., Rivera, J. and Setoain, J. (1991) Intestinal calcium absorption and parathyroid hormone secretion in asthmatic patients on prolonged oral or inhaled steroid treatment. Eur. Respir. J. 4, 441-444.
  6. Paz-Pacheco, E., Fuleihan, G. E. and LeBoff, M. S. (1995) Intact parathyroid hormone levels are not elevated in glucocorticoid-treated subjects. J. Bone Miner Res. 10, 1713-1718. https://doi.org/10.1002/jbmr.5650101114
  7. Hollenberg, S. M., Weinberger, C., Ong, E. S., Cerelli, G., Oro, A., Lebo, R., Thompson, E. B., Rosenfeld, M. G. and Evans, R. M. (1985) Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature 318, 635-641. https://doi.org/10.1038/318635a0
  8. Miesfeld, R., Okret, S., Wikstrom, A. C., Wrange, O., Gustafsson, J. A. and Yamamoto, K. R. (1984) Characterization of a steroid hormone receptor gene and mRNA in wildtype and mutant cells. Nature 312, 779-781. https://doi.org/10.1038/312779a0
  9. Kumar, R. and Thompson, E. B. (2005) Gene regulation by the glucocorticoid receptor: structure: function relationship. J. Steroid. Biochem. Mol. Biol. 94, 383-394. https://doi.org/10.1016/j.jsbmb.2004.12.046
  10. Reichardt, H. M. and Schutz, G. (1998) Glucocorticoid signalling--multiple variations of a common theme. Mol. Cell Endocrinol. 146, 1-6. https://doi.org/10.1016/S0303-7207(98)00208-1
  11. Ruppert, S., Boshart, M., Bosch, F. X., Schmid, W., Fournier, R. E. and Schutz, G. (1990) Two genetically defined transacting loci coordinately regulate overlapping sets of liver-specific genes. Cell 61, 895-904. https://doi.org/10.1016/0092-8674(90)90200-X
  12. Drouin, J., Sun, Y. L., Chamberland, M., Gauthier, Y., De Lean, A., Nemer, M. and Schmidt, T. J. (1993) Novel glucocorticoid receptor complex with DNA element of the hormone-repressed POMC gene. EMBO J. 12, 145-156.
  13. Stromstedt, P. E., Poellinger, L., Gustafsson, J. A. and Carlstedt-Duke, J. (1991) The glucocorticoid receptor binds to a sequence overlapping the TATA box of the human osteocalcin promoter: a potential mechanism for negative regulation. Mol. Cell Biol. 11, 3379-3383. https://doi.org/10.1128/MCB.11.6.3379
  14. Li, C., Li, Y., Liu, H., Sun, Z., Lu, J. and Zhao, Y. (2008) Glucocorticoid repression of human with-no-lysine (K) kinase-4 gene expression is mediated by the negative response elements in the promoter. J. Mol. Endocrinol. 40, 3-12. https://doi.org/10.1677/JME-07-0049
  15. Liberman, A. C., Druker, J., Perone, M. J. and Arzt, E. (2007) Glucocorticoids in the regulation of transcription factors that control cytokine synthesis. Cytokine Growth Factor Rev. 18, 45-56. https://doi.org/10.1016/j.cytogfr.2007.01.005
  16. Liberman, A. C., Druker, J., Refojo, D., Holsboer, F. and Arzt, E. (2009) Glucocorticoids inhibit GATA-3 phosphorylation and activity in T cells. FASEB J. 23, 1558-1571. https://doi.org/10.1096/fj.08-121236
  17. Liberman, A. C., Refojo, D., Druker, J., Toscano, M., Rein, T., Holsboer, F. and Arzt, E. (2007) The activated glucocorticoid receptor inhibits the transcription factor T-bet by direct protein-protein interaction. FASEB J. 21, 1177-1188. https://doi.org/10.1096/fj.06-7452com
  18. Ogawa, S., Lozach, J., Benner, C., Pascual, G., Tangirala, R. K., Westin, S., Hoffmann, A., Subramaniam, S., David, M., Rosenfeld, M. G. and Glass, C. K. (2005) Molecular determinants of crosstalk between nuclear receptors and toll-like receptors. Cell 122, 707-721. https://doi.org/10.1016/j.cell.2005.06.029
  19. Weinstein, R. S., Jilka, R. L., Parfitt, A. M. and Manolagas, S. C. (1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J. Clin. Invest. 102, 274-282. https://doi.org/10.1172/JCI2799
  20. Espina, B., Liang, M., Russell, R. G. and Hulley, P. A. (2008) Regulation of bim in glucocorticoid-mediated osteoblast apoptosis. J. Cell Physiol. 215, 488-496. https://doi.org/10.1002/jcp.21335
  21. Kogianni, G., Mann, V., Ebetino, F., Nuttall, M., Nijweide, P., Simpson, H. and Noble, B. (2004) Fas/CD95 is associated with glucocorticoid-induced osteocyte apoptosis. Life Sci. 75, 2879-2895. https://doi.org/10.1016/j.lfs.2004.04.048
  22. Liu, Y., Encinas, M., Comella, J. X., Aldea, M. and Gallego, C. (2004) Basic helix-loop-helix proteins bind to TrkB and p21(Cip1) promoters linking differentiation and cell cycle arrest in neuroblastoma cells. Mol. Cell Biol. 24, 2662-2672. https://doi.org/10.1128/MCB.24.7.2662-2672.2004
  23. O'Brien, C. A., Jia, D., Plotkin, L. I., Bellido, T., Powers, C. C., Stewart, S. A., Manolagas, S. C. and Weinstein, R. S. (2004) Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology 145, 1835-1841. https://doi.org/10.1210/en.2003-0990
  24. Smith, E., Coetzee, G. A. and Frenkel, B. (2002) Glucocorticoids inhibit cell cycle progression in differentiating osteoblasts via glycogen synthase kinase-3beta. J. Biol. Chem. 277, 18191-18197. https://doi.org/10.1074/jbc.M109708200
  25. Canalis, E. (1996) Clinical review 83: mechanisms of glucocorticoid action in bone: implications to glucocorticoid-induced osteoporosis. J. Clin. Endocrinol. Metab. 81, 3441-3447. https://doi.org/10.1210/jc.81.10.3441
  26. Pereira, R. C., Delany, A. M. and Canalis, E. (2002) Effects of cortisol and bone morphogenetic protein-2 on stromal cell differentiation: correlation with CCAAT-enhancer binding protein expression. Bone 30, 685-691. https://doi.org/10.1016/S8756-3282(02)00687-7
  27. Pereira, R. M., Delany, A. M. and Canalis, E. (2001) Cortisol inhibits the differentiation and apoptosis of osteoblasts in culture. Bone 28, 484-490. https://doi.org/10.1016/S8756-3282(01)00422-7
  28. Ito, S., Suzuki, N., Kato, S., Takahashi, T. and Takagi, M. (2007) Glucocorticoids induce the differentiation of a mesenchymal progenitor cell line, ROB-C26 into adipocytes and osteoblasts, but fail to induce terminal osteoblast differentiation. Bone 40, 84-92. https://doi.org/10.1016/j.bone.2006.07.012
  29. Pereira, R. C., Delany, A. M. and Canalis, E. (2004) CCAAT/enhancer binding protein homologous protein (DDIT3) induces osteoblastic cell differentiation. Endocrinology 145, 1952-1960. https://doi.org/10.1210/en.2003-0868
  30. Wu, Z., Bucher, N. L. and Farmer, S. R. (1996) Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids. Mol. Cell Biol. 16, 4128-4136.
  31. Aubin, J. E. (1999) Osteoprogenitor cell frequency in rat bone marrow stromal populations: role for heterotypic cell-cell interactions in osteoblast differentiation. J. Cell Biochem. 72, 396-410. https://doi.org/10.1002/(SICI)1097-4644(19990301)72:3<396::AID-JCB9>3.0.CO;2-6
  32. Eijken, M., Koedam, M., van Driel, M., Buurman, C. J., Pols, H. A. and van Leeuwen, J. P. (2006) The essential role of glucocorticoids for proper human osteoblast differentiation and matrix mineralization. Mol. Cell Endocrinol. 248, 87-93. https://doi.org/10.1016/j.mce.2005.11.034
  33. Purpura, K. A., Aubin, J. E. and Zandstra, P. W. (2004) Sustained in vitro expansion of bone progenitors is cell density dependent. Stem Cells 22, 39-50. https://doi.org/10.1634/stemcells.22-1-39
  34. Teitelbaum, S. L. (2000) Bone resorption by osteoclasts. Science 289, 1504-1508. https://doi.org/10.1126/science.289.5484.1504
  35. Hofbauer, L. C., Gori, F., Riggs, B. L., Lacey, D. L., Dunstan, C. R., Spelsberg, T. C. and Khosla, S. (1999) Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology 140, 4382-4389. https://doi.org/10.1210/en.140.10.4382
  36. Rubin, J., Biskobing, D. M., Jadhav, L., Fan, D., Nanes, M. S., Perkins, S. and Fan, X. (1998) Dexamethasone promotes expression of membrane-bound macrophage colony-stimulating factor in murine osteoblast-like cells. Endocrinology 139, 1006-1012. https://doi.org/10.1210/en.139.3.1006
  37. Dempster, D. W. (1989) Bone histomorphometry in glucocorticoid-induced osteoporosis. J. Bone Miner Res. 4, 137-141. https://doi.org/10.1002/jbmr.5650040202
  38. Prummel, M. F., Wiersinga, W. M., Lips, P., Sanders, G. T. and Sauerwein, H. P. (1991) The course of biochemical parameters of bone turnover during treatment with corticosteroids. J. Clin. Endocrinol. Metab. 72, 382-386. https://doi.org/10.1210/jcem-72-2-382
  39. Kim, Y. H., Jun, J. H., Woo, K. M., Ryoo, H. M., Kim, G. S. and Baek, J. H. (2006) Dexamethasone inhibits the formation of multinucleated osteoclasts via down-regulation of beta3 integrin expression. Arch. Pharm. Res. 29, 691-698. https://doi.org/10.1007/BF02968254
  40. Kim, H. J., Zhao, H., Kitaura, H., Bhattacharyya, S., Brewer, J. A., Muglia, L. J., Ross, F. P. and Teitelbaum, S. L. (2006) Glucocorticoids suppress bone formation via the osteoclast. J. Clin. Invest. 116, 2152-2160. https://doi.org/10.1172/JCI28084
  41. Jia, D., O'Brien, C. A., Stewart, S. A., Manolagas, S. C. and Weinstein, R. S. (2006) Glucocorticoids act directly on osteoclasts to increase their life span and reduce bone density. Endocrinology 147, 5592-5599. https://doi.org/10.1210/en.2006-0459
  42. Weinstein, R. S., Chen, J. R., Powers, C. C., Stewart, S. A., Landes, R. D., Bellido, T., Jilka, R. L., Parfitt, A. M. and Manolagas, S. C. (2002) Promotion of osteoclast survival and antagonism of bisphosphonate-induced osteoclast apoptosis by glucocorticoids. J. Clin. Invest. 109, 1041-1048. https://doi.org/10.1172/JCI0214538
  43. Teitelbaum, S. L. (2007) Osteoclasts: what do they do and how do they do it? Am. J. Pathol. 170, 427-435. https://doi.org/10.2353/ajpath.2007.060834
  44. Teitelbaum, S. L. and Ross, F. P. (2003) Genetic regulation of osteoclast development and function. Nat. Rev. Genet. 4, 638-649. https://doi.org/10.1038/nrg1122
  45. Faccio, R., Novack, D. V., Zallone, A., Ross, F. P. and Teitelbaum, S. L. (2003) Dynamic changes in the osteoclast cytoskeleton in response to growth factors and cell attachment are controlled by beta3 integrin. J. Cell Biol. 162, 499-509. https://doi.org/10.1083/jcb.200212082
  46. Nakamura, I., Kadono, Y., Takayanagi, H., Jimi, E., Miyazaki, T., Oda, H., Nakamura, K., Tanaka, S., Rodan, G. A. and Duong le, T. (2002) IL-1 regulates cytoskeletal organization in osteoclasts via TNF receptor-associated factor 6/c-Src complex. J. Immunol. 168, 5103-5109. https://doi.org/10.4049/jimmunol.168.10.5103
  47. Sakai, H., Chen, Y., Itokawa, T., Yu, K. P., Zhu, M. L. and Insogna, K. (2006) Activated c-Fms recruits Vav and Rac during CSF-1-induced cytoskeletal remodeling and spreading in osteoclasts. Bone 39, 1290-1301. https://doi.org/10.1016/j.bone.2006.06.012
  48. Ory, S., Brazier, H., Pawlak, G. and Blangy, A. (2008) Rho GTPases in osteoclasts: orchestrators of podosome arrangement. Eur. J. Cell Biol. 87, 469-477. https://doi.org/10.1016/j.ejcb.2008.03.002
  49. Chellaiah, M. A., Soga, N., Swanson, S., McAllister, S., Alvarez, U., Wang, D., Dowdy, S. F. and Hruska, K. A. (2000) Rho-A is critical for osteoclast podosome organization, motility, and bone resorption. J. Biol. Chem. 275, 11993-12002. https://doi.org/10.1074/jbc.275.16.11993
  50. Wang, Y., Lebowitz, D., Sun, C., Thang, H., Grynpas, M. D. and Glogauer, M. (2008) Identifying the relative contributions of Rac1 and Rac2 to osteoclastogenesis. J. Bone Miner Res. 23, 260-270. https://doi.org/10.1359/jbmr.071013
  51. Etienne-Manneville, S. and Hall, A. (2002) Rho GTPases in cell biology. Nature 420, 629-635. https://doi.org/10.1038/nature01148
  52. Hornstein, I., Alcover, A. and Katzav, S. (2004) Vav proteins, masters of the world of cytoskeleton organization. Cell Signal 16, 1-11. https://doi.org/10.1016/S0898-6568(03)00110-4
  53. Rossman, K. L., Der, C. J. and Sondek, J. (2005) GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat. Rev. Mol. Cell Biol. 6, 167-180. https://doi.org/10.1038/nrm1587
  54. Faccio, R., Teitelbaum, S. L., Fujikawa, K., Chappel, J., Zallone, A., Tybulewicz, V. L., Ross, F. P. and Swat, W. (2005) Vav3 regulates osteoclast function and bone mass. Nat. Med. 11, 284-290. https://doi.org/10.1038/nm1194
  55. Patschan, D., Loddenkemper, K. and Buttgereit, F. (2001) Molecular mechanisms of glucocorticoid-induced osteoporosis. Bone 29, 498-505. https://doi.org/10.1016/S8756-3282(01)00610-X
  56. Destaing, O., Saltel, F., Gilquin, B., Chabadel, A., Khochbin, S., Ory, S. and Jurdic, P. (2005) A novel Rho-mDia2-HDAC6 pathway controls podosome patterning through microtubule acetylation in osteoclasts. J. Cell Sci. 118, 2901-2911. https://doi.org/10.1242/jcs.02425
  57. Okumura, S., Mizoguchi, T., Sato, N., Yamaki, M., Kobayashi, Y., Yamauchi, H., Ozawa, H., Udagawa, N. and Takahashi, N. (2006) Coordination of microtubules and the actin cytoskeleton is important in osteoclast function, but calcitonin disrupts sealing zones without affecting microtubule networks. Bone 39, 684-693. https://doi.org/10.1016/j.bone.2006.04.010

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  6. The epithelial sodium channel is involved in dexamethasone-induced osteoblast differentiation and mineralization vol.28, pp.5, 2012, https://doi.org/10.1007/s10565-012-9222-1
  7. Glucocorticoid receptor signaling in bone cells vol.18, pp.6, 2012, https://doi.org/10.1016/j.molmed.2012.04.005
  8. Hypoxia enhances glucocorticoid-induced apoptosis and cell cycle arrest via the PI3K/Akt signaling pathway in osteoblastic cells vol.33, pp.6, 2015, https://doi.org/10.1007/s00774-014-0627-1
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  24. Osteocyte Apoptosis and Lipid Infiltration as Mechanisms of Alcohol-Induced Bone Loss vol.47, pp.4, 2012, https://doi.org/10.1093/alcalc/ags057
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