ArticleArthritis & rheumatology (Hoboken, N.J.)2025
Association of Synovial Innate Immune Exhaustion With Worse Pain in Knee Osteoarthritis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mechanisms of active metabolites from traditional Chinese medicine in osteoarthritis: a critical review.Frontiers in pharmacology · 2026Pooled it
- Spatial multi‑omics identifies an SPP1+ macrophage‑driven anti‑apoptotic niche in osteoarthritis synovium via the SPP1‑CD44 axis.International journal of molecular medicine · 2026Article
- Obesity-Associated Osteoarthritis: Mechanical-Metabolic Pathogenesis, Obesity Memory and Dual-Target Therapy.Current obesity reports · 2026Review
- The Osteoimmunologic Basis of Biologic and Bioengineered Therapies in Osteoarthritis.Biomedicines · 2026Review
- Wnt/β-catenin signaling regulates fibrotic atrophy of intra-articular adipose tissue in post-traumatic osteoarthritis.bioRxiv : the preprint server for biology · 2026Article
- Multimodal Peripheral Blood Immunophenotyping and Single-Cell Epigenetic Analysis of Knee Osteoarthritis Reveals Expansion and Epigenetic Dysregulation of Treg Cell and Nonclassical Monocyte Populations.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- The vicious cycle from inflammation to pyroptosis: the core role of macrophage polarization imbalance in the pathogenesis of knee osteoarthritis.Molecular biology reports · 2026Review
- A Photothermal Transducer Regulates Transmembrane Calcium Flow for Synergistic Osteoarthritis Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Synovial transcriptional clusters link cartilage degeneration to cell-type-specific gene expression in knee osteoarthritis.bioRxiv : the preprint server for biology · 2026Article
- Spatial transcriptomics: challenges and future directions in musculoskeletal diseases.Current opinion in rheumatology · 2026Review
- Targeted Inhibition of CD74Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Osteoarthritis as a systemic disease.Nature reviews. Rheumatology · 2026Review
- Neuropeptide Y signaling in osteoarthritis pain: neuroimmune mechanisms, joint remodeling, and translational opportunities.Frontiers in pain research (Lausanne, Switzerland) · 2026Review
- Mechano-immune interactions in musculoskeletal aging: Mechanisms and translational perspectives.Theranostics · 2026Review
- Epigenetic regulation in osteoarthritis: recent updates and emerging mechanisms.Frontiers in genetics · 2026Review
- Remodeling of senescent macrophages in synovium alleviates trauma- and aging-induced osteoarthritis.Bioactive materials · 2026Article
- Synovial immune control failure in osteoarthritis: from maintenance of tissue homeostasis to inflammatory niche formation.Frontiers in immunology · 2026Review
- Neuroimmune crosstalk in osteoarthritis pain: from synovial inflammation to pain sensitization.Frontiers in immunology · 2026Review
- Article
- Multi-omics analysis unveils inflammatory and metabolic alterations between the synovium and cartilage in patients with knee osteoarthritis.Frontiers in molecular biosciences · 2026Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
objectiveUncontrolled pain remains a major clinical challenge in the management of knee osteoarthritis (OA), the most common disabling joint disease. Worse pain is associated with synovial innate immune cell infiltration (synovitis), but the role of innate immune-regulatory cells in pain is unknown. Our objective was to identify synovial innate immune cell subsets and pathophysiologic mechanisms associated with worse pain in patients with knee OA.
methodsSynovial tissue biopsies from 122 patients with mild-to-severe knee OA pain (Knee Injury and OA Outcome Score [KOOS]) were analyzed to identify associations between synovial histopathology and worse pain. We then used spatial transcriptomics and proteomics of synovial tissue microenvironments (n = 32), followed by single-cell RNA sequencing (n = 8), to identify synovial cell composition and cell-cell communication networks in patients with more severe OA pain.
resultsHistopathological signs of synovial microvascular dysfunction and perivascular edema were associated with worse KOOS pain (-10.76; 95% confidence interval [CI] -18.90 to -2.61). Patients with worse pain had fewer immune-regulatory macrophages, expanded fibroblast subsets, and enrichment in neurovascular remodeling pathways. Synovial macrophages from patients with worse pain expressed markers of immune exhaustion and decreased phagocytic function (-19.42%; 95% CI -35.96 to -2.89) and their conditioned media increased neuronal cell stress in dorsal root ganglia.
conclusionAlthough synovitis increases during OA, our findings suggest that exhaustion, dysfunction, and loss of immune-regulatory macrophages is associated with worse pain and may be an important therapeutic target.
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