Synovial cell cross-talk with cartilage plays a major role in the pathogenesis of osteoarthritis.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
02 07 2020
Historique:
received: 01 02 2020
accepted: 12 06 2020
entrez: 4 7 2020
pubmed: 4 7 2020
medline: 16 12 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 32616761
doi: 10.1038/s41598-020-67730-y
pii: 10.1038/s41598-020-67730-y
pmc: PMC7331607
doi:

Substances chimiques

Biomarkers 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

10868

Subventions

Organisme : NIA NIH HHS
ID : P30 AG028716
Pays : United States

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Auteurs

Ching-Heng Chou (CH)

Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27701, USA.

Vaibhav Jain (V)

Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27701, USA.

Jason Gibson (J)

Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27701, USA.

David E Attarian (DE)

Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, 27701, USA.

Collin A Haraden (CA)

Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27701, USA.

Christopher B Yohn (CB)

Unity Biotechnology, South San Francisco, CA, USA.

Remi-Martin Laberge (RM)

Unity Biotechnology, South San Francisco, CA, USA.

Simon Gregory (S)

Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27701, USA.

Virginia B Kraus (VB)

Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27701, USA. vbk@duke.edu.
Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC, 27701, USA. vbk@duke.edu.

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