ArticleJCI insight2024
Dysregulated fibrinolysis and plasmin activation promote the pathogenesis of osteoarthritis.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 10 citations in OpenAlex.
- SERPINE1/PAI-1 in Skeletal Degeneration: A Proposed Context-Dependent Framework for Bone Remodeling Regulation.Calcified tissue international · 2026Review
- Recent advances in understanding molecular and clinical heterogeneity in osteoarthritis: one disease or several?Osteoarthritis imaging · 2026Article
- T Cells in Osteoarthritis: Drivers, Repairers, or Bystanders in Osteoarthritis?Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Betaine Downregulates RARRES1 to Alleviate Cartilage Fibrosis and Promote Hyaline Cartilage Repair.International journal of molecular sciences · 2026Article
- The activity "blind spot": Why understanding which proteinases are active, not merely present, is essential for rigorous osteoarthritis research.Osteoarthritis and cartilage · 2026Review
- Large-scale molecular endotype discovery in synovial fluid reveals osteoarthritis as a single biological continuum.Nature communications · 2026Article
- Plasminogen Activation System and Fibroblasts: Impact on Tissue Remodeling, Disease, and Organ Homeostasis.Inflammation · 2026Review
- Tranexamic Acid-Associated Hyaluronic Acid Exhibits Enhanced Oxidative Stability: A Comparative Rheological Study.Biomolecules · 2026Article
- Cell culture expansion media choice affects secretory, protective and immuno-modulatory features of adipose mesenchymal stromal cell-derived secretomes for orthopaedic applications.Regenerative therapy · 2025Article
- The Complex Role of Matrix Metalloproteinase-2 (MMP-2) in Health and Disease.International journal of molecular sciences · 2024Review
- Association between arthropathies and postpartum hemorrhage: a bidirectional Mendelian randomization study.Frontiers in genetics · 2024Article
- A single intraarticular injection of a tranexamic acid-modified hyaluronic acid (HA/TXA) alleviates pain and reduces OA development in a murine model of monosodium iodoacetate-induced osteoarthritis.Frontiers in pharmacology · 2024Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Joint injury is associated with risk for development of osteoarthritis (OA). Increasing evidence suggests that activation of fibrinolysis is involved in OA pathogenesis. However, the role of the fibrinolytic pathway is not well understood. Here, we showed that the fibrinolytic pathway, which includes plasminogen/plasmin, tissue plasminogen activator, urokinase plasminogen activator (uPA), and the uPA receptor (uPAR), was dysregulated in human OA joints. Pharmacological inhibition of plasmin attenuated OA progression after a destabilization of the medial meniscus in a mouse model whereas genetic deficiency of plasmin activator inhibitor, or injection of plasmin, exacerbated OA. We detected increased uptake of uPA/uPAR in mouse OA joints by microPET/CT imaging. In vitro studies identified that plasmin promotes OA development through multiple mechanisms, including the degradation of lubricin and cartilage proteoglycans and induction of inflammatory and degradative mediators. We showed that uPA and uPAR produced inflammatory and degradative mediators by activating the PI3K, 3'-phosphoinositide-dependent kinase-1, AKT, and ERK signaling cascades and activated matrix metalloproteinases to degrade proteoglycan. Together, we demonstrated that fibrinolysis contributes to the development of OA through multiple mechanisms and suggested that therapeutic targeting of the fibrinolysis pathway can prevent or slow development of OA.
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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.