ArticleArthritis research & therapy2020
Proteoglycan-4 regulates fibroblast to myofibroblast transition and expression of fibrotic genes in the synovium.
Article in Arthritis research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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Who cites it
37 citing papers in PubMed, 54 citations in OpenAlex.
- YAP/TAZ inhibition refines TGF-β signaling to prevent laryngeal fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Addition of PRG4 to Optimize the Anti-Adhesive Properties of Tissue Barrier SeprafilmAnnals of biomedical engineering · 2026Article
- Lubricin in osteoarthritis: functions and therapeutic prospects.Frontiers in immunology · 2026Review
- Programmed nanozyme hydrogel enabling spatiotemporal modulation of wound healing achieves skin regeneration after biofilm infection.Journal of nanobiotechnology · 2025Article
- Mesenchymal progenitor-derived proteoglycan 4 regulates the transdifferentiation of chondrocytes into osteoblasts during fracture healing.Stem cells translational medicine · 2025Article
- Femur Shape Changes in Prg4-Deficient Mice: Morphological Insights Into Joint Well-Being.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Pathological Changes in Extracellular Matrix Composition Orchestrate the Fibrotic Feedback Loop Through Macrophage Activation in Dupuytren's Contracture.International journal of molecular sciences · 2025Article
- Review
- Differential Gene Expression Analysis in a Lumbar Spinal Stenosis Rat Model via RNA Sequencing: Identification of Key Molecular Pathways and Therapeutic Insights.Biomedicines · 2025Article
- Proteoglycan 4 (Lubricin) and regulation of xanthine oxidase in synovial macrophage as a mechanism of controlling synovitis.Arthritis research & therapy · 2024Article
- Interleukin receptor therapeutics attenuate inflammation in canine synovium following cruciate ligament injury.Osteoarthritis and cartilage · 2024Article
- Review
- Proteoglycan 4 (Lubricin) and Regulation of Xanthine Oxidase in Synovial Macrophage as A Mechanism of Controlling Synovitis.Research square · 2024Article
- Thrombospondin-1 promotes fibro-adipogenic stromal expansion and contractile dysfunction of the diaphragm in obesity.JCI insight · 2024Article
- Synovial Membrane Is a Major Producer of Extracellular Inorganic Pyrophosphate in Response to Hypoxia.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Fibrotic pathways and fibroblast-like synoviocyte phenotypes in osteoarthritis.Frontiers in immunology · 2024Review
- Modulating mechanobiology as a therapeutic target for synovial fibrosis to restore joint lubrication.Osteoarthritis and cartilage · 2024Article
- Targeting CD44 Receptor Pathways in Degenerative Joint Diseases: Involvement of Proteoglycan-4 (PRG4).Pharmaceuticals (Basel, Switzerland) · 2023Review
- Minoxidil weakens newly synthesized collagen in fibrotic synoviocytes from osteoarthritis patients.Journal of experimental orthopaedics · 2023Article
- Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundSynovial tissue fibrosis is common in advanced OA with features including the presence of stress fiber-positive myofibroblasts and deposition of cross-linked collagen type-I. Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and is a major component of synovial fluid. PRG4 is a ligand of the CD44 receptor. Our objective was to examine the role of PRG4-CD44 interaction in regulating synovial tissue fibrosis in vitro and in vivo.
methodsOA synoviocytes were treated with TGF-β ± PRG4 for 24 h and α-SMA content was determined using immunofluorescence. Rhodamine-labeled rhPRG4 was incubated with OA synoviocytes ± anti-CD44 or isotype control antibodies and cellular uptake of rhPRG4 was determined following a 30-min incubation and α-SMA expression following a 24-h incubation. HEK-TGF-β cells were treated with TGF-β ± rhPRG4 and Smad3 phosphorylation was determined using immunofluorescence and TGF-β/Smad pathway activation was determined colorimetrically. We probed for stress fibers and focal adhesions (FAs) in TGF-β-treated murine fibroblasts and fibroblast migration was quantified ± rhPRG4. Synovial expression of fibrotic markers: α-SMA, collagen type-I, and PLOD2 in Prg4 gene-trap (Prg4
resultsPRG4 reduced α-SMA content in OA synoviocytes (p < 0.001). rhPRG4 was internalized by OA synoviocytes via CD44 and CD44 neutralization attenuated rhPRG4's antifibrotic effect (p < 0.05). rhPRG4 reduced pSmad3 signal in HEK-TGF-β cells (p < 0.001) and TGF-β/Smad pathway activation (p < 0.001). rhPRG4 reduced the number of stress fiber-positive myofibroblasts, FAs mean size, and cell migration in TGF-β-treated NIH3T3 fibroblasts (p < 0.05). rhPRG4 inhibited fibroblast migration in a macrophage and fibroblast co-culture model without altering active or total TGF-β levels. Synovial tissues of 9-month-old Prg4
conclusionPRG4 is an endogenous antifibrotic modulator in the joint and its effect on myofibroblast formation is partially mediated by CD44, but CD44 is not required to demonstrate an antifibrotic effect in vivo.
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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 Socratic graph.