Kinetics of gene expression and bone remodelling in the clinical phase of collagen-induced arthritis
Open accessAbstract
Introduction: Pathological bone changes differ considerably between inflammatory arthritic diseases and most studies have focused on bone erosion. Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis, which, in addition to bone erosion, demonstrates bone formation at the time of clinical manifestations. The objective of this study was to use this model to characterise the histological and molecular changes in bone remodelling, and relate these to the clinical disease development. Methods: A histological and gene expression profiling time-course study on bone remodelling in CIA was linked to onset of clinical symptoms. Global gene expression was studied with a gene chip array system. Results: The main histopathological changes in bone structure and inflammation occurred during the first two weeks following the onset of clinical symptoms in the joint. Hereafter, the inflammation declined and remodelling of formed bone dominated. Global gene expression profiling showed simultaneous upregulation of genes related to bone changes and inflammation in week 0 to 2 after onset of clinical disease. Furthermore, we observed time-dependent expression of genes involved in early and late osteoblast differentiation and function, which mirrored the histopathological bone changes. The differentially expressed genes belong to the bone morphogenetic pathway (BMP) and, in addition, include the osteoblast markers integrin-binding sialoprotein (Ibsp), bone gamma-carboxyglutamate protein (Bglap1), and secreted phosphoprotein 1 (Spp1). Pregnancy-associated protein A (Pappa) and periostin (Postn), differentially expressed in the early disease phase, are proposed to participate in bone formation, and we suggest that they play a role in early bone formation in the CIA model. Comparison to human genome-wide association studies (GWAS) revealed differential expression of several genes associated with human arthritis. Conclusions: In the CIA model, bone formation in the joint starts shortly after onset of clinical symptoms, which results in bony fusion within one to two weeks. This makes it a candidate model for investigating the relationship between inflammation and bone formation in inflammatory arthritis.
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Both TBX3 and TBX5 are involved in bone development and remodeling.
“Among other functions, both proteins are involved in bone development [18–20] and remodeling [21].”
From The oncoprotein TBX3 is controlling severity in experimental arthritis (2019) · cites this paper as [21]
The Results and Discussion discuss bone formation and remodelling in collagen-induced arthritis, but the passages found do not address TBX3 or TBX5. Searches for “TBX3 TBX5 bone development remodeling” and “T-box transcription factors Tbx3 Tbx5” found no passage linking either protein to those processes. (LLM, conf=0.76)
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Molecular genetic and epigenetic analysis of osteoarthritis
Rogers, E. L. (2017)
Mohammadi, H., & Najafi, A. (2024) · Annual report. · doi:10.61186/rap.15.4.83
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- Authors
- Denninger, K. C., Litman, T., Marstrand, T., Moller, K., Svensson, L., Labuda, T., & Andersson, Å.
- Affiliations
- University of Copenhagen (DK)
- Leo Pharma (Denmark) (DK)
- Corresponding author
- Denninger, Katja CM
- Venue
- Arthritis Research & Therapy
- Published
- 2015-03-05
- Volume
- 17
- Issue
- 1
- Pages
- 43-43
- ISSN
- 1478-6354 (ISSN-L)
- PMC
- PMC4391727
- OpenAlex
- W1977128211
- Cited by
- 27
- References
- 63
- Citations by year
- 2025: 3 · 2024: 2 · 2022: 1 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 6
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Arthritis Research & Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- Funders
- LEO Pharma
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- collagen-induced arthritis, bone remodeling, bone formation, rheumatoid arthritis, gene expression profiling, osteogenic differentiation, bone morphogenetic proteins, periostin, osteopontin, joint inflammation, disease onset, bony fusion, inflammatory arthritis
- MeSH terms
- Animals, Arthritis, Experimental, Cell Differentiation, Collagen, Gene Expression Regulation, Male, Mice, Inbred DBA, RNA, Polymerase Chain Reaction, Bone Remodeling, Bone Morphogenetic Proteins, Gene Expression Profiling
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