ArticleArthritis research & therapy2018
Recombinant human proteoglycan-4 reduces phagocytosis of urate crystals and downstream nuclear factor kappa B and inflammasome activation and production of cytokines and chemokines in human and murine macrophages.
Article in Arthritis research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Lubricin in experimental and naturally occurring osteoarthritis: a systematic review.Osteoarthritis and cartilage · 2020Pooled it
- Addition of PRG4 to Optimize the Anti-Adhesive Properties of Tissue Barrier SeprafilmAnnals of biomedical engineering · 2026Article
- Disruption of proteoglycan 4 (PRG4)-CD44 signaling modulates chronic synovitis in conditionally inactivated mice.Arthritis research & therapy · 2026Article
- Advances in post-translational and epigenetic modification of hyperuricemia-to-gout progression: mechanisms and therapeutic targets.Frontiers in cell and developmental biology · 2026Review
- Synovial fluid alpha-2-macroglobulin, gelsolin and lubricin distinguish between osteoarthritic and healthy equine joints.Equine veterinary journal · 2026Article
- Lubricin's Mucin Domain Has Strong Polyproline Type II Helical Character.Computational and structural biotechnology journal · 2026Article
- Modulating the gut-bladder axis: fecal transplantation protects antibiotic-treated mice from E. coli cystitis via the Ahr/Prg4 pathway.Microbiome · 2025Article
- Disruption of Proteoglycan 4 (PRG4)-CD44 Signaling Modulates Chronic Synovitis in Conditionally Inactivated Mice.Research square · 2025Article
- TMT-based quantitative proteomics analysis of serum-derived exosomes in patients with juvenile gout.Frontiers in endocrinology · 2025Article
- Hyperuricemia-induced complications: dysfunctional macrophages serve as a potential bridge.Frontiers in immunology · 2025Review
- Exposing kinetic disparities between inflammasome readouts using time-resolved analysis.Heliyon · 2024Article
- Zerumbone reduces TLR2 stimulation-induced M1 macrophage polarization pattern via upregulation of Nrf-2 expression in murine macrophages.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- WTAP Mediated N6-methyladenosine RNA Modification of ELF3 Drives Cellular Senescence by Upregulating IRF8.International journal of biological sciences · 2024Article
- Targeting CD44 Receptor Pathways in Degenerative Joint Diseases: Involvement of Proteoglycan-4 (PRG4).Pharmaceuticals (Basel, Switzerland) · 2023Review
- Amplification of Inflammation by Lubricin Deficiency Implicated in Incident, Erosive Gout Independent of Hyperuricemia.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- Proteoglycan 4 (PRG4) treatment enhances wound closure and tissue regeneration.NPJ Regenerative medicine · 2022Article
- Quadruped Gait and Regulation of Apoptotic Factors in Tibiofemoral Joints following Intra-Articular rhPRG4 Injection inInternational journal of molecular sciences · 2022Article
- Noncovalent hyaluronan crosslinking by TSG-6: Modulation by heparin, heparan sulfate, and PRG4.Frontiers in molecular biosciences · 2022Article
- Inflammatory Response to Regulated Cell Death in Gout and Its Functional Implications.Frontiers in immunology · 2022Review
- Proteoglycan-4 is an essential regulator of synovial macrophage polarization and inflammatory macrophage joint infiltration.Arthritis research & therapy · 2021Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundGout is an inflammatory arthritis caused by monosodium urate monohydrate (MSU) crystals' joint deposition. MSU phagocytosis by resident macrophages is a key step in gout pathogenesis. MSU phagocytosis triggers nuclear factor kappa B (NFκB) activation and production of cytokines and chemokines. Proteoglycan-4 (PRG4) is a glycoprotein produced by synovial fibroblasts and exerts an anti-inflammatory effect in the joint mediated by its interaction with cell surface receptor CD44. PRG4 also binds and antagonizes TLR2 and TLR4. The objective of this study is to evaluate the efficacy of recombinant human PRG4 (rhPRG4) in suppressing MSU-induced inflammation and mechanical allodynia in vitro and in vivo.
methodsTHP-1 macrophages were incubated with MSU crystals ± rhPRG4 or bovine submaxillary mucin (BSM), and crystal phagocytosis, cytokines and chemokines expression and production were determined. NFκB p65 subunit nuclear translocation, NLRP3 induction, caspase-1 activation and conversion of proIL-1β to mature IL-1β were studied. MSU phagocytosis by Prg4
resultsrhPRG4 reduced MSU crystal phagocytosis at 4 h (p < 0.01) and IL-1β, TNF-α, IL-8 and MCP-1 expression and production at 6 h (p < 0.05). BSM did not alter MSU phagocytosis or IL-1β production in human and murine macrophages. rhPRG4 treatment reduced NFκB nuclear translocation, NLRP3 expression, caspase-1 activation and generation of mature IL-1β (p < 0.05). MSU-stimulated IL-1β production was higher in Prg4
conclusionrhPRG4 inhibits MSU crystal phagocytosis and exhibits an anti-inflammatory and anti-nociceptive activity in vitro and in vivo. rhPRG4's anti-inflammatory mechanism may be due to targeting CD44 on macrophages.
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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.