ArticleNature medicine2011
Identification of a central role for complement in osteoarthritis.
Article in Nature medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 321 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
321 citing papers in PubMed, 2 syntheses or guidelines pooled it, 558 citations in OpenAlex.
- Pooled it
- An Evidence-Based Systematic Review of Human Knee Post-Traumatic Osteoarthritis (PTOA): Timeline of Clinical Presentation and Disease Markers, Comparison of Knee Joint PTOA Models and Early Disease Implications.International journal of molecular sciences · 2021Pooled it
- Complement Expression and Activation in Osteoarthritis Joint Compartments.Frontiers in immunology · 2020Trial
- Management of Musculoskeletal Injuries with an Inflammatory Damage-Associated Molecular Pattern (DAMP) Etiology.Pain and therapy · 2026Review
- Selenium, Selenoprotein P, and Gut Dysbiosis are Associated with Cartilage Damage in Osteoarthritis Patients.Biological trace element research · 2026Article
- Selenium, Selenoprotein P, and Gut Dysbiosis are Associated with Cartilage Damage in Osteoarthritis Patients.Biological trace element research · 2026Article
- T Cells in Osteoarthritis: Drivers, Repairers, or Bystanders in Osteoarthritis?Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Advances in Complement Research: from Pathophysiology to Precision Medicine.Physiology (Bethesda, Md.) · 2026Review
- Recent advances in understanding molecular and clinical heterogeneity in osteoarthritis: one disease or several?Osteoarthritis imaging · 2026Article
- The Potential Role of Synovial T Cell Infiltration Following Knee Joint Injury in Symptoms and Progression to Osteoarthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Senescence-Associated Checkpoint Gene Dysregulation in Established Osteoarthritis: Integrated Transcriptomic Analysis and In Vitro Evaluation of CDK6 and WEE1.Biomedicines · 2026Article
- Large-scale molecular endotype discovery in synovial fluid reveals osteoarthritis as a single biological continuum.Nature communications · 2026Article
- The evolving landscape of complement therapeutics in rheumatology.Annals of the rheumatic diseases · 2026Review
- Article
- Systemic implications of osteoarthritis: from local degeneration to systemic metabolic Dysregulation.Journal of translational medicine · 2026Review
- Vasoactive intestinal peptide advances chondrogenesis and modulates pathogenic mediators in human osteoarthritis.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Targeting adipocyte ESRRA alleviates osteoarthritis via interrupting inter-organelle crosstalk of complement C3-CFD-MAC cascade.Bone research · 2026Article
- Integrative analysis of single-cell and bulk RNA sequencing data using machine learning identifies PTGDS as a key subsynovial fibroblast gene in osteoarthritis.Journal of molecular histology · 2026Article
- Mesenchymal stem cell exosomes alleviate osteoarthritis by inhibiting complement activation via a CD59-dependent pathway.Arthritis research & therapy · 2026Article
- The osteoarthritis inflammatory ecosystem: a node-edge-boundary-emergent framework toward precision stratification and therapeutic hypothesis generation.Frontiers in medicine · 2026Review
261 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 11 institutions in 3 countries.
Funding
Abstract
Osteoarthritis, characterized by the breakdown of articular cartilage in synovial joints, has long been viewed as the result of 'wear and tear'. Although low-grade inflammation is detected in osteoarthritis, its role is unclear. Here we identify a central role for the inflammatory complement system in the pathogenesis of osteoarthritis. Through proteomic and transcriptomic analyses of synovial fluids and membranes from individuals with osteoarthritis, we find that expression and activation of complement is abnormally high in human osteoarthritic joints. Using mice genetically deficient in complement component 5 (C5), C6 or the complement regulatory protein CD59a, we show that complement, specifically, the membrane attack complex (MAC)-mediated arm of complement, is crucial to the development of arthritis in three different mouse models of osteoarthritis. Pharmacological modulation of complement in wild-type mice confirmed the results obtained with genetically deficient mice. Expression of inflammatory and degradative molecules was lower in chondrocytes from destabilized joints from C5-deficient mice than C5-sufficient mice, and MAC induced production of these molecules in cultured chondrocytes. Further, MAC colocalized with matrix metalloprotease 13 (MMP13) and with activated extracellular signal-regulated kinase (ERK) around chondrocytes in human osteoarthritic cartilage. Our findings indicate that dysregulation of complement in synovial joints has a key role in the pathogenesis of osteoarthritis.
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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.