ArticleArthritis & rheumatology (Hoboken, N.J.)2015
Lubricin/Proteoglycan 4 Binding to CD44 Receptor: A Mechanism of the Suppression of Proinflammatory Cytokine-Induced Synoviocyte Proliferation by Lubricin.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- Lubricin in experimental and naturally occurring osteoarthritis: a systematic review.Osteoarthritis and cartilage · 2020Pooled it
- Tissue Damage in Rheumatoid Arthritis Is Genetically Linked to Low Peptidylglycine Alpha-Amidating Monooxygenase Activity in Synovial Fibroblasts.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Cellular crosstalk and signaling networks in the rheumatoid arthritis synovial microenvironment.Journal of translational medicine · 2026Review
- Defining subcellular synovial responses in TMJ osteoarthritis onset via mechanical stress and articular disk derangement models.International journal of oral science · 2026Article
- Disruption of proteoglycan 4 (PRG4)-CD44 signaling modulates chronic synovitis in conditionally inactivated mice.Arthritis research & therapy · 2026Article
- Lubricin in osteoarthritis: functions and therapeutic prospects.Frontiers in immunology · 2026Review
- Proteoglycan-4 potentiates the antitumor efficacy of regorafenib in an orthotopic model of hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Lectin Microarray-based Glycomics and Machine Learning Identify Shared Osteoarthritis Biomarkers in Humans, Dogs, and Horses.bioRxiv : the preprint server for biology · 2025Article
- Disruption of Proteoglycan 4 (PRG4)-CD44 Signaling Modulates Chronic Synovitis in Conditionally Inactivated Mice.Research square · 2025Article
- Uncovering Cellular Interactome Drivers of Immune Checkpoint Inhibitor Response in Advanced Melanoma Patients.Cellular and molecular bioengineering · 2025Article
- Intra-Articular Administration of Recombinant Human Proteoglycan 4 (rhPRG4) as a Potential Therapy for Temporomandibular Joint Osteoarthritis: A Preclinical Histopathological Study.International journal of molecular sciences · 2025Article
- Mesenchymal progenitor-derived proteoglycan 4 regulates the transdifferentiation of chondrocytes into osteoblasts during fracture healing.Stem cells translational medicine · 2025Article
- Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis.Nature communications · 2025Article
- Molecular Mechanisms and Therapeutic Role of Intra-Articular Hyaluronic Acid in Osteoarthritis: A Precision Medicine Perspective.Journal of clinical medicine · 2025Review
- Postnatal deletion of Phlpp1 in chondrocytes delays post-traumatic osteoarthritis in male mice.Osteoarthritis and cartilage open · 2025Article
- Transcriptomic responses of lung mesenchymal cells during pneumonia.JCI insight · 2025Article
- Proteoglycan 4 (Lubricin) and regulation of xanthine oxidase in synovial macrophage as a mechanism of controlling synovitis.Arthritis research & therapy · 2024Article
- Massive parallel sequencing of head and neck conventional squamous cell carcinomas: A comprehensive review.Virchows Archiv : an international journal of pathology · 2024Review
- Proteoglycan 4 (Lubricin) and Regulation of Xanthine Oxidase in Synovial Macrophage as A Mechanism of Controlling Synovitis.Research square · 2024Article
- Regenerative capacity of human pluripotent stem cell-derived articular chondrocytes in vitro.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2024Article
23 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
7 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveTo evaluate the binding of recombinant human proteoglycan 4 (rhPRG4) to CD44 receptor and its consequences on cytokine-induced synoviocyte proliferation.
methodsThe binding of rhPRG4 to CD44 and competition with high molecular weight (HMW) hyaluronic acid (HA) was evaluated using a direct enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance. Sialidase A and O-glycosidase digestion of rhPRG4 was performed, and CD44 binding was evaluated using ELISA. Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) were stimulated with interleukin-1β (IL-1β) or tumor necrosis factor α (TNFα) for 48 hours in the presence or absence of rhPRG4 or HMW HA at 20, 40, and 80 μg/ml, and cell proliferation was measured. The contribution of CD44 was assessed by coincubation with a CD44 antibody (IM7). The antiproliferative effect of rhPRG4 was investigated following treatment of PRG4(-/-) mouse synoviocytes with IL-1β or TNFα in the presence or absence of IM7.
resultsRecombinant human PRG4 bound CD44 and interfered with the binding of HMW HA to CD44. Removal of sialic acid and O-glycosylations significantly increased CD44 binding by rhPRG4 (P < 0.001). Both rhPRG4 and HMW HA at 40 and 80 μg/ml significantly suppressed IL-1β-induced proliferation of RA FLS (P < 0.05). Recombinant human PRG4 at 20, 40, and 80 μg/ml significantly suppressed TNFα-induced RA FLS proliferation (P < 0.05). CD44 neutralization reversed the effect of rhPRG4 on IL-1β- and TNFα-stimulated RA FLS and the effect of HMW HA on IL-1β-stimulated RA FLS. Recombinant human PRG4 inhibited cytokine-induced proliferation of PRG4(-/-) synoviocytes, which could be prevented by blocking CD44.
conclusionPRG4 (lubricin) is a novel putative ligand for CD44 and may control synoviocyte overgrowth in inflammatory arthropathies via a CD44-mediated mechanism.
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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.