ArticleAnnals of the rheumatic diseases2016
Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in vivo.
Article in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Role of Agrin in tissue repair and regeneration: From mechanisms to therapeutic opportunities (Review).International journal of molecular medicine · 2024Pooled it
- The role of agrin as a downstream mediator of Slit3 in osteogenic-angiogenic interaction under osteoporosis.Regenerative biomaterials · 2026Article
- Chondrocyte fatty acid oxidation drives osteoarthritis via SOX9 degradation and epigenetic regulation.Nature communications · 2025Article
- Glycosaminoglycans, Instructive Biomolecules That Regulate Cellular Activity and Synaptic Neuronal Control of Specific Tissue Functional Properties.International journal of molecular sciences · 2025Review
- Extracellular matrix: Dystroglycan interactions-Roles for the dystrophin-associated glycoprotein complex in skeletal tissue dynamics.International journal of experimental pathology · 2025Review
- LRP4 and Agrin Are Modulated by Cartilage Degeneration and Involved in β-Catenin Signaling in Human Articular Chondrocytes.International journal of molecular sciences · 2025Article
- Gut microbiota and blood biomarkers in IBD-Related arthritis: insights from mendelian randomization.Scientific reports · 2025Article
- Innate immune pathway activation to modulate mesenchymal stromal cell (MSC) interactions with synovium and cartilage.Frontiers in bioengineering and biotechnology · 2025Article
- Effect of Passaging on Bovine Chondrocyte Gene Expression and Engineered Cartilage Production.Tissue engineering. Part A · 2024Article
- Lamc1 promotes osteogenic differentiation and inhibits adipogenic differentiation of bone marrow-derived mesenchymal stem cells.Scientific reports · 2024Article
- The Current State of Extracellular Matrix Therapy for Ischemic Heart Disease.Medical sciences (Basel, Switzerland) · 2024Review
- Chemokines in Cartilage Regeneration and Degradation: New Insights.International journal of molecular sciences · 2023Review
- The Glycosaminoglycan Side Chains and Modular Core Proteins of Heparan Sulphate Proteoglycans and the Varied Ways They Provide Tissue Protection by Regulating Physiological Processes and Cellular Behaviour.International journal of molecular sciences · 2023Review
- Article
- Disease modification and symptom relief in osteoarthritis using a mutated GCP-2/CXCL6 chemokine.EMBO molecular medicine · 2023Article
- Deconstruction of Neurotrypsin Reveals a Multi-factorially Regulated Activity Affecting Myotube Formation and Neuronal Excitability.Molecular neurobiology · 2022Article
- TRPV4 activation enhances compressive properties and glycosaminoglycan deposition of equine neocartilage sheets.Osteoarthritis and cartilage open · 2022Article
- In vivo potency assay for the screening of bioactive molecules on cartilage formation.Lab animal · 2022Review
- Digoxin targets low density lipoprotein receptor-related protein 4 and protects against osteoarthritis.Annals of the rheumatic diseases · 2022Article
- Injectable amnion hydrogel-mediated delivery of adipose-derived stem cells for osteoarthritis treatment.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
Abstract
objectivesOsteoarthritis (OA) is a leading cause of disability for which there is no cure. The identification of molecules supporting cartilage homeostasis and regeneration is therefore a major pursuit in musculoskeletal medicine. Agrin is a heparan sulfate proteoglycan which, through binding to low-density lipoprotein receptor-related protein 4 (LRP4), is required for neuromuscular synapse formation. In other tissues, it connects the cytoskeleton to the basement membrane through binding to α-dystroglycan. Prompted by an unexpected expression pattern, we investigated the role and receptor usage of agrin in cartilage.
methodsAgrin expression pattern was investigated in human osteoarthritic cartilage and following destabilisation of the medial meniscus in mice. Extracellular matrix (ECM) formation and chondrocyte differentiation was studied in gain and loss of function experiments in vitro in three-dimensional cultures and gain of function in vivo, using an ectopic cartilage formation assay in nude mice. Receptor usage was investigated by disrupting LRP4 and α-dystroglycan by siRNA and blocking antibodies respectively.
resultsAgrin was detected in normal cartilage but was progressively lost in OA. In vitro, agrin knockdown resulted in reduced glycosaminoglycan content, downregulation of the cartilage transcription factor SOX9 and other cartilage-specific ECM molecules. Conversely, exogenous agrin supported cartilage differentiation in vitro and ectopic cartilage formation in vivo. In the context of cartilage differentiation, agrin used an unusual receptor repertoire requiring both LRP4 and α-dystroglycan.
conclusionsWe have discovered that agrin strongly promotes chondrocyte differentiation and cartilage formation in vivo. Our results identify agrin as a novel potent anabolic growth factor with strong therapeutic potential in cartilage regeneration.
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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.