ArticleJCI insight2018
An aggrecan fragment drives osteoarthritis pain through Toll-like receptor 2.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- 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
- Management of Musculoskeletal Injuries with an Inflammatory Damage-Associated Molecular Pattern (DAMP) Etiology.Pain and therapy · 2026Review
- Review
- Glycosaminoglycans in tissue regeneration: Insights into glycobiology and their biomedical application.Bioactive materials · 2026Review
- Emerging concepts in osteoarthritis and musculoskeletal diseases: Insights from the University of Debrecen Musculoskeletal Symposium 2025.Osteoarthritis and cartilage open · 2026Article
- Bridging Temporomandibular Joint Structure, Function, and Pain: An Integrated Multiscale Perspective.Journal of dental research · 2026Review
- FM-dye inhibition of Piezo2 relieves mechanically evoked pain in mouse models of acute inflammatory and osteoarthritic knee pain.British journal of pharmacology · 2026Article
- Neuroimmune crosstalk in osteoarthritis pain: from synovial inflammation to pain sensitization.Frontiers in immunology · 2026Review
- Proteoglycans as Biomarkers of Medial Degeneration in Acute Stanford Type A Aortic Dissection.Reviews in cardiovascular medicine · 2025Review
- Not Just Neurons: Pain Is Orchestrated in Partnership with Many Non-neuronal Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- COMP Is a Biomarker of Cartilage Destruction, Extracellular Matrix and Vascular Remodeling and Tissue Repair.International journal of molecular sciences · 2025Review
- Metabolomic and proteomic stratification of equine osteoarthritis.Equine veterinary journal · 2025Article
- MicroRNA-322 Attenuates Cartilage Matrix Degradation in Osteoarthritis via Direct Suppression of TRAF3.Cartilage · 2025Article
- Expression of thrombospondin-4 in the infrapatellar fat pad and synovial fluid - potential contribution to osteoarthritis pain.Arthritis research & therapy · 2025Article
- Pain Assessment in Osteoarthritis: Present Practices and Future Prospects Including the Use of Biomarkers and Wearable Technologies, and AI-Driven Personalized Medicine.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2025Review
- Assessment of Knee Hyperalgesia in Mice using Pressure Application Measurement.Journal of visualized experiments : JoVE · 2025Article
- Association of Synovial Innate Immune Exhaustion With Worse Pain in Knee Osteoarthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Which Endpoints Should be Applied in Interventional Trials? -: From Single Uni-dimensional Assessment Tailored to a Drug's Mechanism of Action to Multi-Component Measures and Multi-Domain Composites.Osteoarthritis imaging · 2025Article
- Beyond the Surface: Nutritional Interventions Integrated with Diagnostic Imaging Tools to Target and Preserve Cartilage Integrity: A Narrative Review.Biomedicines · 2025Review
- Osteoarthritis.Nature reviews. Disease primers · 2025Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Pain is the predominant symptom of osteoarthritis, but the connection between joint damage and the genesis of pain is not well understood. Loss of articular cartilage is a hallmark of osteoarthritis, and it occurs through enzymatic degradation of aggrecan by cleavage mediated by a disintegrin and metalloproteinase with thrombospondin motif 4 (ADAMTS-4) or ADAMTS-5 in the interglobular domain (E373-374A). Further cleavage by MMPs (N341-342F) releases a 32-amino-acid aggrecan fragment (32-mer). We investigated the role of this 32-mer in driving joint pain. We found that the 32-mer excites dorsal root ganglion nociceptive neurons, both in culture and in intact explants. Treatment of cultured sensory neurons with the 32-mer induced expression of the proalgesic chemokine CCL2. These effects were mediated through TLR2, which we demonstrated was expressed by nociceptive neurons. In addition, intra-articular injection of the 32-mer fragment provoked knee hyperalgesia in WT but not Tlr2-null mice. Blocking the production or action of the 32-mer in transgenic mice prevented the development of knee hyperalgesia in a murine model of osteoarthritis. These findings suggest that the aggrecan 32-mer fragment directly activates TLR2 on joint nociceptors and is an important mediator of the development of osteoarthritis-associated joint pain.
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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.