Glucocorticoid excess in mice results in early activation of osteoclastogenesis and adipogenesis and prolonged suppression of osteogenesis: a longitudinal study of gene expression in bone tissue from glucocorticoid-treated mice
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OBJECTIVE: Glucocorticoid (GC) excess induces alterations in bone metabolism that weaken bone structure and increase fracture risk. The aim of this study was to identify genes associated with bone metabolism in GC-treated mice, by performing a microarray analysis. METHODS: Long bones from mice exposed to GC excess were collected after 0, 7, 28, and 56 days of treatment, to measure bone microarchitecture and extract RNA for microarray analyses. RESULTS: Bone loss in this animal model was confirmed by changes in bone turnover markers as well as bone architecture, as measured by microfocal computed tomography. GC excess induced an early up-regulation of genes involved in osteoclast activation, function, and adipogenesis, which peaked on day 7. The expression of genes associated with osteoclast cytoskeletal reorganization and genes associated with matrix degradation peaked on day 28. On day 28 and day 56, the expression of genes associated with osteoblast activation and maturation was decreased from baseline, while the expression of Wnt antagonists was increased. In addition, the expression of genes expressed in osteocytes associated with bone mineralization was significantly higher at the later time points, day 28 and day 56. Reverse transcription-polymerase chain reaction confirmed the results of microarray analysis in selected genes. CONCLUSION: GC excess is associated with early activation of genes associated with osteoclastogenesis and adipogenesis and a later suppression of genes associated with osteogenesis and mineralization. Novel interventions with agents that modulate either Wnt signaling or mineralization may be effective in GC-induced osteoporosis.
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Glucocorticoid-induced inhibition of osteoblasts occurs through multiple mechanisms.
“through GC induced inhibition of osteoblasts through multiple mechanisms [34]”
From Prevention of glucocorticoid induced bone changes with beta-ecdysone (2015) · cites this paper as [34]
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Self-citation
- Authors
- Yao, W., Cheng, Z., Busse, C., Pham, A., Nakamura, M. C., & Lane, N. E.
- Affiliations
- University of California Davis Medical Center (US)
- University of California, San Francisco (US)
- Corresponding author
- Lane, Nancy E.
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2008-05-31
- Volume
- 58
- Issue
- 6
- Pages
- 1674-1686
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- PMC
- PMC3892702
- OpenAlex
- W2062447638
- Cited by
- 241
- References
- 51
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 8 · 2023: 10 · 2022: 11 · 2021: 17 · 2020: 8 · 2019: 23 · 2018: 23 · 2017: 12 · 2016: 19 · 2015: 9 · 2014: 11 · 2013: 16 · 2012: 12
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR043052, K24AR048841, 1-K24-AR-48841-02)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD051958)
- 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 › Genetics › Estrogen and related hormone effects
- Keywords
- glucocorticoid excess, glucocorticoid-induced osteoporosis, osteoclastogenesis, adipogenesis, bone formation, bone metabolism, gene expression, Wnt signaling, osteocytes, bone mineralization, bone turnover markers, bone microarchitecture, osteoblast maturation, matrix degradation
- MeSH terms
- Animals, Bone and Bones, Cell Differentiation, Disease Models, Animal, Gene Expression Regulation, Glucocorticoids, Male, Osteoclasts, Osteogenesis, Prednisolone, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Adipogenesis, Mice
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