ArticleJCI insight2020
Neutrophil extracellular traps mediate articular cartilage damage and enhance cartilage component immunogenicity in rheumatoid arthritis.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 184 citations in OpenAlex.
- Meta-analysis of the Relationship Between Zinc and Copper in Patients with Osteoarthritis.Biological trace element research · 2025Pooled it
- Neutrophil extracellular trap suppression in rheumatoid arthritis patients treated with biologic therapy: a prospective observational study.Clinical rheumatology · 2026Article
- Autoantibodies and T Cells Target Citrullinated and Homocitrullinated Antigens in Rheumatoid Arthritis.Immunological reviews · 2026Review
- Adventitial root extract of oplopanax elatus alleviates rheumatoid arthritis via inhibiting NETosis.Clinical rheumatology · 2026Article
- Psoriasis patients with psoriatic arthritis demonstrate a reduced regulatory capacity for neutrophil elastase.Rheumatology (Oxford, England) · 2026Article
- Cell death crosstalk in NET-Driven inflammation: mechanisms, disease contexts, and therapeutic perspectives.Biomarker research · 2026Review
- IntradiscalJOR spine · 2026Article
- Dual roles of neutrophil extracellular traps in tumors: From pro-metastatic mechanisms to immunotherapeutic strategies (Review).Oncology letters · 2026Review
- An exploratory Mendelian randomization study on the genetically predicted effects of circulating blood cells on osteoarthritis risk.Clinics (Sao Paulo, Brazil) · 2026Article
- Deficiency of interleukin-40 prevents intestinal damage in experimental necrotizing enterocolitis by inhibiting NETosis.Cell communication and signaling : CCS · 2026Article
- Article
- The Role of Immune Infiltration and Oxidative Stress in the Progression of Cerebral Cavernous Malformation.Brain and behavior · 2026Review
- Neutrophil extracellular traps in rheumatoid arthritis: biomarkers, drivers, and emerging therapeutic targets.Clinical and experimental immunology · 2026Review
- Altered neutrophil signalling linked to impaired chemotaxis and increased ROS and NET production in older people with frailty.Clinical and experimental immunology · 2026Article
- A comprehensive insight into NETosis-extracellular vesicle crosstalk in autoimmune diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Gut microbiota dysbiosis in rheumatoid arthritis: mechanisms linking intestinal barrier dysfunction to synovial inflammation.Frontiers in immunology · 2026Review
- Oral Contraceptive Pill Use is Associated with Lower Levels of Plasma Calprotectin in Premenopausal Women.Frontiers in lupus · 2026Article
- Immunomodulatory effects of oral microbiota in the pathogenesis of rheumatoid arthritis.Frontiers in immunology · 2026Review
- Interactions between neutrophil extracellular traps and macrophages: the key to inflammatory diseases.Frontiers in immunology · 2026Review
- Autophagy inhibitors block pathogenic NET release in immune-mediated inflammatory disease without impairing host defence.Rheumatology (Oxford, England) · 2025Article
56 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Rheumatoid arthritis (RA) is characterized by synovial joint inflammation, cartilage damage, and dysregulation of the adaptive immune system. While neutrophil extracellular traps (NETs) have been proposed to play a role in the generation of modified autoantigens and in the activation of synovial fibroblasts, it remains unknown whether NETs are directly involved in cartilage damage. Here, we report a new mechanism by which NET-derived elastase disrupts cartilage matrix and induces release of membrane-bound peptidylarginine deiminase-2 by fibroblast-like synoviocytes (FLSs). Cartilage fragments are subsequently citrullinated, internalized by FLSs, and then presented to antigen-specific CD4+ T cells. Furthermore, immune complexes containing citrullinated cartilage components can activate macrophages to release proinflammatory cytokines. HLA-DRB1*04:01 transgenic mice immunized with NETs develop autoantibodies against citrullinated cartilage proteins and display enhanced cartilage damage. Inhibition of NET-derived elastase rescues NET-mediated cartilage damage. These results show that NETs and neutrophil elastase externalized in these structures play fundamental pathogenic roles in promoting cartilage damage and synovial inflammation. Strategies targeting neutrophil elastase and NETs could have a therapeutic role in RA and in other inflammatory diseases associated with inflammatory joint damage.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.