ArticleOsteoarthritis and cartilage2026
Cross-platform transcriptomic data integration identifies an overactive neuro-immune signature in human osteoarthritis synovium.
Article in Osteoarthritis and cartilage, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- EZH2 coordinates inflammatory and pain-associated pathways across joint compartments in osteoarthritis.Molecular biomedicine · 2026Article
- TNFRSF10B Implicated in Osteoarthritis Protection via the Alpha-Tocopherol-to-Sulfate Ratio: A Multiomics and Mendelian Randomization Study.International journal of molecular sciences · 2026Article
- Wnt/β-catenin signaling regulates fibrotic atrophy of intra-articular adipose tissue in post-traumatic osteoarthritis.bioRxiv : the preprint server for biology · 2026Article
- Leptin drives osteoarthritis pain through sensory neuron reprogramming independent of cartilage signaling.bioRxiv : the preprint server for biology · 2026Article
- Synovial fibroblasts modulate endothelial activation in an acute injury-on-a-chip model.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- TNFSF13 insufficiency disrupts human colonic epithelial cell growth and associated B cell dynamics.The Journal of clinical investigation · 2026Article
- Mapping the Extended Pain Pathway: Human Genetic and Multi-Omic Strategies for Next-Generation Analgesics.International journal of molecular sciences · 2026Review
- Osteoarthritis as a systemic disease.Nature reviews. Rheumatology · 2026Review
- Neuroimmune crosstalk in osteoarthritis pain: from synovial inflammation to pain sensitization.Frontiers in immunology · 2026Review
- Psychological stress and gut microbiota regulation of osteoarthritis progression: mechanisms and therapeutic strategies.Frontiers in microbiology · 2026Review
- LOXL1, THY1, and TYMS define an annotation-derived hemoglobin-associated immunotranscriptomic signature in osteoarthritis cartilage.Frontiers in immunology · 2026Article
- Combined multi-omics approach to identify the key metabolites, key microorganisms and biomarkers correlated with the neutrophil extracellular traps-associated gene TIMP1 in osteoarthritis.Frontiers in pharmacology · 2025Article
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Authors and funding
10 authors.
Funding
Abstract
objectiveChronic synovitis is associated with osteoarthritis (OA) pain, but the molecular underpinnings remain unclear. Our objective was to characterize the transcriptional phenotype of OA synovium with a focus on signaling relevant to pain.
designEight publicly-available microarray and RNA-sequencing GEO datasets from human non-OA and OA subjects underwent quality control and re-analysis for differentially-expressed genes (DEGs). Cross-platform statistical integration was performed via a weighted Z-test to combine detection power across datasets. Gene set enrichment, cell type enrichment, and regulon analyses were performed. Human single-cell RNA sequencing data was used to map gene expression to cell types. Ligand-receptor interactions were predicted via multi-omic data from human dorsal root ganglia (DRG).
resultsFollowing statistical integration of individual studies (N=153 total subjects, N=139 after quality control), gene set enrichment analysis identified 276 differentially-activated pathway terms in OA synovium, including strong enrichment for pathways related to innate and adaptive immunity (notably MHC Class II) and fibrotic remodeling-relevant extracellular matrix organization. VEGF signaling and angiogenesis-related terms were downregulated. Enriched pain and neuronal pathways primarily related to neuro-immune interactions, including neuroinflammation, and were associated with macrophages, B and T lymphocytes, and synovial fibroblasts. A gene regulatory network comprised of STAT1, FLI1, and VDR putatively governed the expression of 27 genes driving neuro-immune signaling. An unbiased synovium-DRG interactome predicted 76 potential interactions between synovial cells and DRG nociceptors, involving 68 neuronal receptors interacting with 32 ligands overexpressed in OA synovium.
conclusionsEnd-stage OA synovium is markedly enriched for neuroinflammatory and neuro-immune signaling, putatively governed by STAT1, FLI1, and VDR.
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