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Glucocorticoids suppress bone formation via the osteoclast.
Open accessAbstract
The pathogenesis of glucocorticoid-induced (GC-induced) bone loss is unclear. For example, osteoblast apoptosis is enhanced by GCs in vivo, but they stimulate bone formation in vitro. This conundrum suggests that an intermediary cell transmits a component of the bone-suppressive effects of GCs to osteoblasts in the intact animal. Bone remodeling is characterized by tethering of the activities of osteoclasts and osteoblasts. Hence, the osteoclast is a potential modulator of the effect of GCs on osteoblasts. To define the direct impact of GCs on bone-resorptive cells, we compared the effects of dexamethasone (DEX) on WT osteoclasts with those derived from mice with disruption of the GC receptor in osteoclast lineage cells (GRoc-/- mice). While the steroid prolonged longevity of osteoclasts, their bone-degrading capacity was suppressed. The inhibitory effect of DEX on bone resorption reflects failure of osteoclasts to organize their cytoskeleton in response to M-CSF. DEX specifically arrested M-CSF activation of RhoA, Rac, and Vav3, each of which regulate the osteoclast cytoskeleton. In all circumstances GRoc-/- mice were spared the impact of DEX on osteoclasts and their precursors. Consistent with osteoclasts modulating the osteoblast-suppressive effect of DEX, GRoc-/- mice are protected from the steroid's inhibition of bone formation.
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“DEX was recently shown to prolong the lifespan of osteoclasts, while decreasing their individual capacity to degrade bone (257).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [257]
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Cites
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
Lacey, D. L., Timms, E., Tan, H.-L., Kelley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81569-x · Cited by 5,439
Bone Resorption by Osteoclasts
Teitelbaum, S. L. (2000) · Science · doi:10.1126/science.289.5484.1504 · Cited by 3,962
Conditional gene targeting in macrophages and granulocytes using LysMcre mice
Clausen, B. E., Burkhardt, C., Reith, W., Renkawitz, R., & Förster, I. (1999) · Transgenic Research · doi:10.1023/a:1008942828960 · Cited by 2,098
Weinstein, R. S., Jilka, R. L., Parfitt, A. M., & Manolagas, S. C. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2799 · Cited by 1,753 · cited 1×
“Net bone mass represents the relative activities of osteoblasts and osteoclasts, and there is little question that GCs suppress bone-forming cells, in vivo, via a process involving accelerated apoptosis (1, 2).”
BackgroundSeverely Suppressed Bone Turnover: A Potential Complication of Alendronate Therapy
Odvina, C. V., Zerwekh, J. E., Rao, D. S., Maalouf, N. M., Gottschalk, F., & Pak, C. Y. C. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0952 · Cited by 1,429
c-Fos: a Key Regulator of Osteoclast-Macrophage Lineage Determination and Bone Remodeling
Grigoriadis, A. E., Wang, Z., Cecchini, M. G., Hofstetter, W., Felix, R., Fleisch, H. A., & Wagner, E. F. (1994) · Science · doi:10.1126/science.7939685 · Cited by 1,264
Black, D. M., Greenspan, S. L., Ensrud, K. E., Palermo, L., McGowan, J., Lang, T., Garnero, P., Bouxsein, M., Bilezikian, J. P., & Rosen, C. J. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa031975 · Cited by 1,168
Udagawa, N., Takahashi, N., Akatsu, T., Tanaka, H., Sasaki, T., Nishihara, T., Koga, T., Martin, T. J., & Suda, T. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.18.7260 · Cited by 1,048
The Effects of Parathyroid Hormone, Alendronate, or Both in Men with Osteoporosis
Finkelstein, J. S., Hayes, A.-M., Hunzelman, J. L., Wyland, J. J., Lee, H., & Neer, R. M. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa035725 · Cited by 823
IL-1 mediates TNF-induced osteoclastogenesis
Shi, W., Kitaura, H., Zhou, P., Ross, F. P., & Teitelbaum, S. L. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23394 · Cited by 805
Hofbauer, L. C., Gori, F., Riggs, B. L., Lacey, D. L., Dunstan, C. R., Spelsberg, T. C., & Khosla, S. (1999) · Endocrinology · doi:10.1210/endo.140.10.7034 · Cited by 794
Mice lacking beta3 integrins are osteosclerotic because of dysfunctional osteoclasts.
McHugh, K. P., Hodivala-Dilke, K., Zheng, M., Namba, N., Lam, J. D., Novack, D., Feng, X., Ross, F., Hynes, R. O., & Teitelbaum, S. L. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8905 · Cited by 786
Osteoclast-derived activity in the coupling of bone formation to resorption
Martin, T. J., & Sims, N. A. (2005) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2004.12.004 · Cited by 661
Rickard, D. J., Sullivan, T. A., Shenker, B. J., Leboy, P. S., & Kazhdan, I. (1994) · Developmental Biology · doi:10.1006/dbio.1994.1022 · Cited by 537
Weinstein, R. S., Chen, J., Powers, C. C., Stewart, S. A., Landes, R. D., Bellido, T., Jilka, R. L., PARFITT, A. M., & Manolagas, S. C. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14538 · Cited by 397
New Developments in the Pathogenesis and Treatment of Steroid-Induced Osteoporosis
Manolagas, S. C., & Weinstein, R. S. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.7.1061 · Cited by 382
Perspectives bone histomorphometry in glucocorticoid-induced osteoporosis
Dempster, D. W. (1989) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650040202 · Cited by 319
Vav3 regulates osteoclast function and bone mass
Faccio, R., Teitelbaum, S., Fujikawa, K., Chappel, J., Zallone, A., Tybulewicz, V., Ross, F., & Swat, W. (2005) · Nature Medicine · doi:10.1038/nm1194 · Cited by 304
Decreased C-Src Expression Enhances Osteoblast Differentiation and Bone Formation
Marzia, M., Sims, N. A., Voit, S., Migliaccio, S., Taranta, A., Bernardini, S., Faraggiana, T., Yoneda, T., Mundy, G. R., Boyce, B. F., et al. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.2.311 · Cited by 285
Rho-A Is Critical for Osteoclast Podosome Organization, Motility, and Bone Resorption
Chellaiah, M. A., Soga, N., Swanson, S., McAllister, S., Alvarez, U., Wang, D., Dowdy, S. F., & Hruska, K. A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.16.11993 · Cited by 263
THE SCIENCE AND THERAPY OF GLUCOCORTICOID-INDUCED BONE LOSS
Lane, N. E., & Lukert, B. P. (1998) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(05)70017-7 · Cited by 209
The Course of Biochemical Parameters of Bone Turnover during Treatment with Corticosteroids
Prummel, M. F., Wiersinga, W. M., Lips, P. T. A. M., Sanders, G. T., & Sauerwein, H. P. (1991) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-72-2-382 · Cited by 202
c-Fms and the αvβ3 integrin collaborate during osteoclast differentiation
Faccio, R., Takeshita, S., Zallone, A. Z., Ross, F. P., & Teitelbaum, S. L. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16924 · Cited by 195
Fast glucocorticoid actions on brain: Back to the future
Dallman, M. F. (2005) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2005.08.001 · Cited by 192
Rubin, M. R., & Bilezikian, J. P. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-012101 · Cited by 191
Glucocorticoid-Induced Osteoporosis
Weinstein, R. S. (2001) · Reviews in Endocrine and Metabolic Disorders · doi:10.1023/a:1010007108155 · Cited by 187
Corticosteroid-Induced Bone Loss in Men
Pearce, G., Tabensky, D. A., Delmas, P. D., Baker, H. W. G., & Seeman, E. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.3.4621 · Cited by 184
Faccio, R., Novack, D. V., Zallone, A. Z., Ross, F. P., & Teitelbaum, S. L. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200212082 · Cited by 178
c-Fms and the αvβ3 integrin collaborate during osteoclast differentiation
Faccio, R., Takeshita, S., Zallone, A. Z., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200316924 · Cited by 171
Cortisol inhibits the differentiation and apoptosis of osteoblasts in culture
Pereira, R. M. R., Delany, A. M., & CANALIS, E. M. (2001) · Bone · doi:10.1016/s8756-3282(01)00422-7 · Cited by 166
Pereira, R. C., Delany, A. M., & CANALIS, E. M. (2002) · Bone · doi:10.1016/s8756-3282(02)00687-7 · Cited by 163
Black, D. M., Greenspan, S. L., Ensrud, K. E., Palermo, L., McGowan, J., Lang, T., Garnero, P., Bouxsein, M., Bilezikian, J. P., & Rosen, C. J. (2004) · Obstetrical & Gynecological Survey · doi:10.1097/01.ogx.0000115856.54444.d6 · Cited by 159
T-cell glucocorticoid receptor is required to suppress COX-2-mediated lethal immune activation
Brewer, J. A., Khor, B., Vogt, S. K., Muglia, L. M., Fujiwara, H., Haegele, K. E., Sleckman, B. P., & Muglia, L. J. (2003) · Nature Medicine · doi:10.1038/nm895 · Cited by 149
Rubin, J., Biskobing, D. M., Jadhav, L., Fan, D., Nanes, M. S., Perkins, S., & Fan, X. (1998) · Endocrinology · doi:10.1210/endo.139.3.5778 · Cited by 113
Anabolic Actions of Parathyroid Hormone during Bone Growth Are Dependent on c-fos
Demiralp, B., Chen, H.-L., Koh, A. J., Keller, E. T., & McCauley, L. K. (2002) · Endocrinology · doi:10.1210/en.2002-220221 · Cited by 112
Effect of corticosteroids on human osteoclast formation and activity
HIRAYAMA, T., Sabokbar, A., & Athanasou, N. A. (2002) · Journal of Endocrinology · doi:10.1677/joe.0.1750155 · Cited by 99
Regulation of Actin Ring Formation by Rho GTPases in Osteoclasts
Chellaiah, M. A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500154200 · Cited by 87
The Skeletal Effects of Glucocorticoid Excess Override Those of Orchidectomy in Mice
Weinstein, R. S., Jia, D., Powers, C. C., Stewart, S. A., Jilka, R. L., PARFITT, A. M., & Manolagas, S. C. (2004) · Endocrinology · doi:10.1210/en.2003-1133 · Cited by 86
Sustained In Vitro Expansion of Bone Progenitors Is Cell Density Dependent
Purpura, K. A., Aubin, J. E., & Zandstra, P. W. (2004) · Stem Cells · doi:10.1634/stemcells.22-1-39 · Cited by 85
Nakamura, I., Kadono, Y., Takayanagi, H., Jimi, E., Miyazaki, T., Oda, H., Nakamura, K., Tanaka, S., Rodan, G. A., & Duong, L. T. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.10.5103 · Cited by 61
Martelli, A. M., Cocco, L., Bareggi, R., Tabellini, G., Rizzoli, R., Ghibellini, M. D., & Narducci, P. (1999) · Journal of Cellular Biochemistry · doi:10.1002/(sici)1097-4644(19990301)72:3 · Cited by 38
Glucocorticoid-induced osteoporosis
Kumar, R. (2001) · Current Opinion in Nephrology & Hypertension · doi:10.1097/00041552-200109000-00007 · Cited by 37
Rubin, J. E. (1998) · Endocrinology · doi:10.1210/en.139.3.1006 · Cited by 35
Weinstein, R. S., Chen, J., Powers, C. C., Stewart, S. A., Landes, R. D., Bellido, T., Jilka, R. L., PARFITT, A. M., & Manolagas, S. C. (2002) · Journal of Clinical Investigation · doi:10.1172/jci200214538 · Cited by 25
Rac1 and Rac2 GTPases Play Distinct Roles and Are Essential for Full Osteoclast Differentiation.
Korhonen, M. O., Zhao, H., Faccio, R., Ross, F. P., Hopkins, T., Cancelas, J. A., Teitelbaum, S. L., & Williams, D. A. (2005) · Blood · doi:10.1182/blood.v106.11.67.67 · Cited by 3
Rac1 and Rac2 GTPases Play Distinct Roles and Are Essential for Full Osteoclast Differentiation.
Korhonen, M. O., Zhao, H., Faccio, R., Ross, P. F., Hopkins, T., Cancelas, J. A., & Williams, D. A. (2006) · Blood · doi:10.1182/blood.v108.11.4231.4231 · Cited by 2
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Feng, X., & McDonald, J. M. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130203 · Cited by 1,272
“(121, 122) recently showed that GCs exert a direct inhibitory effect on osteoclast function (Figure 4f ).”
BackgroundGlucocorticoid-induced osteoporosis: pathophysiology and therapy
CANALIS, E. M., Mazziotti, G., Giustina, A., & Bilezikian, J. P. (2007) · Osteoporosis International · doi:10.1007/s00198-007-0394-0 · Cited by 1,131
“The direct effects of glucocorticoids on osteoclasts also may contribute to an operational decline in osteoblast function during glucocorticoid exposure [35].”
BackgroundSkeletal remodeling in health and disease
Zaidi, M. (2007) · Nature Medicine · doi:10.1038/nm1593 · Cited by 1,069
“More recently, it has been shown that osteoclasts are necessary for glucocorticoid-induced osteoblast inhibitio”
BackgroundInflammatory bone loss: pathogenesis and therapeutic intervention
Redlich, K., & Smolen, J. S. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3669 · Cited by 846
“Importantly, although these agents are highly effective at reducing or blocking the inflammatory process, they are also major mediators of osteoporosis as they heavily interfere with bone remodellin”
BackgroundKearns, A. E., Khosla, S., & Kostenuik, P. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0014 · Cited by 824
Metadata
- Authors
- Kim, H.-J.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Kim, H.-J.
- ORCID
- Kim, H.-J.
- Venue
- Journal of Clinical Investigation
- Published
- 2006-08-01
- Volume
- 116
- Issue
- 8
- Pages
- 2152-2160
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1518793
- OpenAlex
- W2102680446
- Cited by
- 384
- References
- 47
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 7 · 2023: 11 · 2022: 16 · 2021: 23 · 2020: 22 · 2019: 21 · 2018: 21 · 2017: 9 · 2016: 17 · 2015: 25 · 2014: 18 · 2013: 12 · 2012: 25
- FWCI
- 11.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- National Institutes of Health (DK 056341, AR046523)
- National Institute of Allergy and Infectious Diseases (AI50655, R01AI050655, R21AI050655)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 056341, P30DK056341)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 048853, AR 046852, AR 032788, R01AR048812, AR 048812, R01AR032788, R37AR046523, AR046523, R01AR048853, R01AR046852, R01AR046523)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- glucocorticoids, glucocorticoid-induced osteoporosis, osteoclasts, bone formation, dexamethasone, glucocorticoid receptor, RhoA, Rac, Vav3, osteoclast precursors, bone remodeling, osteoblast apoptosis
- MeSH terms
- Animals, Bone Development, Bone Resorption, Cell Survival, Dexamethasone, Glucocorticoids, Osteoclasts, Receptors, Glucocorticoid, Mice, Knockout, Mice
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