Synovial cell cross-talk with cartilage plays a major role in the pathogenesis of osteoarthritis
Open accessAbstract
We elucidated the molecular cross-talk between cartilage and synovium in osteoarthritis, the most widespread arthritis in the world, using the powerful tool of single-cell RNA-sequencing. Multiple cell types were identified based on profiling of 10,640 synoviocytes and 26,192 chondrocytes: 12 distinct synovial cell types and 7 distinct articular chondrocyte phenotypes from matched tissues. Intact cartilage was enriched for homeostatic and hypertrophic chondrocytes, while damaged cartilage was enriched for prefibro- and fibro-, regulatory, reparative and prehypertrophic chondrocytes. A total of 61 cytokines and growth factors were predicted to regulate the 7 chondrocyte cell phenotypes. Based on production by > 1% of cells, 55% of the cytokines were produced by synovial cells (39% exclusive to synoviocytes and not expressed by chondrocytes) and their presence in osteoarthritic synovial fluid confirmed. The synoviocytes producing IL-1beta (a classic pathogenic cytokine in osteoarthritis), mainly inflammatory macrophages and dendritic cells, were characterized by co-expression of surface proteins corresponding to HLA-DQA1, HLA-DQA2, OLR1 or TLR2. Strategies to deplete these pathogenic intra-articular cell subpopulations could be a therapeutic option for human osteoarthritis.
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- Authors
- Chou, C.-H., Jain, V., Gibson, J., Attarian, D. E., Haraden, C. A., Yohn, C. B., Laberge, R.-M., Gregory, S., & Kraus, V. B.
- Affiliations
- Duke University (US)
- Unity Biotechnology (United States) (US)
- Corresponding author
- Kraus, Virginia B.
- ORCID
- Venue
- Scientific Reports
- Published
- 2020-07-02
- Volume
- 10
- Issue
- 1
- Pages
- 10868-10868
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7331607
- OpenAlex
- W3039453617
- Cited by
- 398
- References
- 64
- Citations by year
- 2026: 73 · 2025: 77 · 2024: 79 · 2023: 56 · 2022: 58 · 2021: 54 · 2020: 1
- FWCI
- 31.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AG028716)
- National Institute on Aging (NIA P30AG028716, AG028716, P30AG028716)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Keywords
- osteoarthritis, synovium, cartilage, synoviocytes, chondrocytes, synovial fluid, cytokines, growth factors, IL-1β, macrophages, dendritic cells, HLA-DQA1, HLA-DQA2, OLR1, TLR2, chondrocyte phenotype, intercellular communication, single-cell RNA sequencing
- MeSH terms
- Synoviocytes, RNA-Seq, Aged, Cartilage, Articular, Cells, Cultured, Female, Humans, Male, Osteoarthritis, Biomarkers, Case-Control Studies
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