The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
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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Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
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“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
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c-Fos: a Key Regulator of Osteoclast-Macrophage Lineage Determination and Bone Remodeling
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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
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“The direct effects of glucocorticoids on osteoclasts also may contribute to an operational decline in osteoblast function during glucocorticoid exposure [35].”
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“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
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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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