ArticleArthritis research & therapy2024
Proteoglycan 4 (Lubricin) and regulation of xanthine oxidase in synovial macrophage as a mechanism of controlling synovitis.
Article in Arthritis research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Addition of PRG4 to Optimize the Anti-Adhesive Properties of Tissue Barrier SeprafilmAnnals of biomedical engineering · 2026Article
- Parameter-screened LED therapy targets STAT3/IL-6 axis to attenuate tendinopathy via dual modulation of inflammation and ECM remodeling.Journal of orthopaedic surgery and research · 2026Article
- Disruption of proteoglycan 4 (PRG4)-CD44 signaling modulates chronic synovitis in conditionally inactivated mice.Arthritis research & therapy · 2026Article
- Proteoglycan-4 (PRG4) serum concentration is lower in aged mice, and genetic deficiency impacts survival probability, blood parameters, and bone during aging.GeroScience · 2026Article
- How Selective are Nanomaterials to Treat Osteoarthritis.International journal of nanomedicine · 2026Review
- Diagnostic Utility of Extracellular Levels of Serum Amyloid P and Proteoglycan 4: A Case-Control Study in Gestational Diabetes Mellitus.International journal of general medicine · 2026Article
- Three-dimensionally-printed biphasic PCL/Regenerative biomaterials · 2026Article
- Lubricin in osteoarthritis: functions and therapeutic prospects.Frontiers in immunology · 2026Review
- Disruption of Proteoglycan 4 (PRG4)-CD44 Signaling Modulates Chronic Synovitis in Conditionally Inactivated Mice.Research square · 2025Article
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7 authors.
Funding
Abstract
backgroundSynovial macrophages (SMs) are important effectors of joint health and disease. A novel Cx3CR1 + TREM2 + SM population expressing the tight junction protein claudin-5, was recently discovered in synovial lining. Ablation of these SMs was associated with onset of arthritis. Proteoglycan 4 (PRG4) is a mucinous glycoprotein that fulfills lubricating and homeostatic roles in the joint. The aim of this work is to study the role of PRG4 in modulating synovitis in the context of SM homeostasis and assess the contribution of xanthine oxidase (XO)-hypoxia inducible factor alpha (HIF-1a) axis to this regulation.
methodsWe used Prg4
resultsPrg4 inactivation induced Cx3CR1 + TREM2 + SM loss (p < 0.001) and upregulated glycolysis and innate immune pathways in the synovium. In isolated SMs, Xdh (p < 0.01) and Hif1a (p < 0.05) were upregulated. Pro-inflammatory activation of SMs was evident by enhanced glycolytic flux and XO-generated reactive oxygen species (ROS). Febuxostat reduced glycolytic flux (p < 0.001) and HIF-1a levels (p < 0.0001) in SMs. Febuxostat also reduced systemic inflammation (p < 0.001), synovial hyperplasia (p < 0.001) and preserved Cx3CR1 + TREM2 + SMs (p < 0.0001) in synovia of Prg4 inactivated mice.
conclusionsPRG4 is a biologically significant modulator of synovial homeostasis via inhibition of XO expression and downstream HIF-1a activation. PRG4 signaling is anti-inflammatory and promotes synovial homeostasis in chronic synovitis, where direct XO inhibition is potentially therapeutic in chronic synovitis.
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