Anatomy

Phenotype

Pathology

Cell

Cytokine

Pathogenesis

Biology

Gene

TLR4

Synovial fluid

Cell type

Immunology

Alternative medicine

Osteoarthritis

Inflammation

Arthritis

Synovial membrane

Cartilage

TLR2

Chondrocyte

Cell biology

Genetics

Medicine

Scientific Reports

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 &gt; 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.

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