| Autor: |
Chou CH; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27701, USA., Jain V; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27701, USA., Gibson J; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27701, USA., Attarian DE; Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, 27701, USA., Haraden CA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27701, USA., Yohn CB; Unity Biotechnology, South San Francisco, CA, USA., Laberge RM; Unity Biotechnology, South San Francisco, CA, USA., Gregory S; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27701, USA., 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. |
| Abstrakt: |
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. |
