Spatial architecture of the synovium identifies clinically relevant phenotypes of osteoarthritis
Authors' conclusion
These findings indicate that the spatial organization of synovial architecture, beyond simple tissue composition, captures clinically relevant heterogeneity in knee OA and links histological microenvironments to cell-cell communication networks.
Study context
- Population
- Patients with knee osteoarthritis (OA); hematoxylin and eosin-stained whole-slide images of human synovium
- Outcome
- OA-associated histological features identified by the model
Methodological detailsspatial entropy and inter-tissue connectivity metrics, graph neural network-based community modeling, integration with matched synovial single-cell RNA sequencing data
- Spatial entropy and inter-tissue connectivity metrics
- Graph neural network-based community modeling
- Integration with matched synovial single-cell RNA sequencing data
Main finding
As reported in the abstract
- Synovial lining hyperplasia, immune cell infiltration, angiogenesis, and fibrotic remodeling identified
Further findings
Dense fibrous tissue enrichment and postoperative outcomes
- Enrichment of dense fibrous tissue was associated with poorer postoperative outcomes
- Tissue proportion alone did not adequately capture baseline disease status
Lining-Micro vessel interactions and preoperative KOOS Symptom scores and synovitis scores
- Enrichment of Lining-Micro vessel interactions was associated with lower preoperative KOOS Symptom scores, indicating more severe symptoms, and elevated synovitis scores
Micro vessel communities (graph neural network-based modeling)
- Micro vessels segregated into two distinct communities, one enriched in adjacent lining structures and another associated with immune-rich regions; relative abundances varied among knee OA patients
Lining fibroblast-endothelial cell interactions (single-cell RNA sequencing)
- Increased predicted interactions between lining fibroblasts and endothelial cells in the Lining-Micro vessel-rich phenotype, enriched for angiogenesis-related VEGF and ANGPTL signaling
Original publication
Spatial architecture of the synovium identifies clinically relevant phenotypes of osteoarthritis. Osteoarthritis Cartilage. Published 4 November 2026. doi:10.
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