ArticleThe Journal of clinical investigation2003
Essential role for proteinase-activated receptor-2 in arthritis.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
114 citing papers in PubMed, 335 citations in OpenAlex.
- Article
- Rivaroxaban suppresses factor Xa-Driven PAR-2-ERK inflammatory, catabolic, osteoclastogenic, and mitochondrial dysfunction signaling in osteoarthritis-relevant chondrocytes: a drug-repurposing strategy for joint inflammation.Frontiers in pharmacology · 2026Article
- A New Strategy in Modulating the Protease-Activated Receptor 2 (Par2) in Autoimmune Diseases.International journal of molecular sciences · 2025Review
- Targeting PAR2-mediated inflammation in osteoarthritis: a comprehensive in vitro evaluation of oleocanthal's potential as a functional food intervention for chondrocyte protection and anti-inflammatory effects.BMC musculoskeletal disorders · 2024Article
- Beyond Anticoagulation: A Comprehensive Review of Non-Vitamin K Oral Anticoagulants (NOACs) in Inflammation and Protease-Activated Receptor Signaling.International journal of molecular sciences · 2024Review
- The Genetic Landscape of Systemic Rheumatic Diseases: A Comprehensive Multigene-Panel Study Identifying Key Gene Polymorphisms.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Tryptase and Exogenous Trypsin: Mechanisms and Ophthalmic Applications.Journal of inflammation research · 2023Review
- Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Differential Expression and Distinct Roles of Proteinase-Activated Receptor 2 in Microglia and Neurons in Neonatal Mouse Brain After Hypoxia-Ischemic Injury.Molecular neurobiology · 2022Article
- Protease Activated Receptors and Arthritis.International journal of molecular sciences · 2021Review
- Protease activated receptor 2 and matriptase expression in the joints of cats with and without osteoarthritis.Journal of feline medicine and surgery · 2021Article
- Spinal PAR2 Activation Contributes to Hypersensitivity Induced by Peripheral Inflammation in Rats.International journal of molecular sciences · 2021Article
- Article
- Discovery of Novel Nonpeptidic PAR2 Ligands.ACS medicinal chemistry letters · 2020Article
- Down-regulation of protease-activated receptor 2 ameliorated osteoarthritis in rats through regulation of MAPK/NF-κB signaling pathway in vivo and in vitro.Bioscience reports · 2020Article
- Proteinase-Mediated Macrophage Signaling in Psoriatic Arthritis.Frontiers in immunology · 2020Article
- Proteinase‑activated receptor 2 deficiency is a protective factor against cardiomyocyte apoptosis during myocardial ischemia/reperfusion injury.Molecular medicine reports · 2019Article
- High Affinity Fluorescent Probe for Proteinase-Activated Receptor 2 (PAR2).ACS medicinal chemistry letters · 2019Article
- Collagenolytic matrix metalloproteinases antagonize proteinase-activated receptor-2 activation, providing insights into extracellular matrix turnover.The Journal of biological chemistry · 2019Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Using physiological, pharmacological, and gene disruption approaches, we demonstrate that proteinase-activated receptor-2 (PAR-2) plays a pivotal role in mediating chronic inflammation. Using an adjuvant monoarthritis model of chronic inflammation, joint swelling was substantially inhibited in PAR-2-deficient mice, being reduced by more than fourfold compared with wild-type mice, with virtually no histological evidence of joint damage. Mice heterozygous for PAR-2 gene disruption showed an intermediate phenotype. PAR-2 expression, normally limited to endothelial cells in small arterioles, was substantially upregulated 2 weeks after induction of inflammation, both in synovium and in other periarticular tissues. PAR-2 agonists showed potent proinflammatory effects as intra-articular injection of ASKH95, a novel synthetic PAR-2 agonist, induced prolonged joint swelling and synovial hyperemia. Given the absence of the chronic inflammatory response in the PAR-2-deficient mice, our findings demonstrate a key role for PAR-2 in mediating chronic inflammation, thereby identifying a novel and important therapeutic target for the management of chronic inflammatory diseases such as rheumatoid arthritis.
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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.