ArticleArthritis research & therapy2015
The interaction of lubricin/proteoglycan 4 (PRG4) with toll-like receptors 2 and 4: an anti-inflammatory role of PRG4 in synovial fluid.
Article in Arthritis research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 2 of them syntheses that pooled it.
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Who cites it
86 citing papers in PubMed, 2 syntheses or guidelines pooled it, 136 citations in OpenAlex.
- Fighting Bleb Fibrosis After Glaucoma Surgery: Updated Focus on Key Players and Novel Targets for Therapy.International journal of molecular sciences · 2025Pooled it
- Lubricin in experimental and naturally occurring osteoarthritis: a systematic review.Osteoarthritis and cartilage · 2020Pooled it
- Effects of Dietary Selenium Sources on Meat Quality, Tissue Selenium Deposition, and Transcriptome Profiling ofFoods (Basel, Switzerland) · 2026Article
- Systemic and local autoantibody responses to extracellular matrix proteins define inflammatory phenotypes across arthropathies.Rheumatology (Oxford, England) · 2026Article
- Lubricin maintains temporomandibular joint homeostasis by regulating synovial inflammation.Regenerative therapy · 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
- Synovial fluid alpha-2-macroglobulin, gelsolin and lubricin distinguish between osteoarthritic and healthy equine joints.Equine veterinary journal · 2026Article
- Lubricin in osteoarthritis: functions and therapeutic prospects.Frontiers in immunology · 2026Review
- Modulating the gut-bladder axis: fecal transplantation protects antibiotic-treated mice from E. coli cystitis via the Ahr/Prg4 pathway.Microbiome · 2025Article
- Proteoglycan 4 attenuates ischemic post-stroke hemorrhagic transformation and blood-brain barrier disruption.IBRO neuroscience reports · 2025Article
- Exercise as Osteoarthritis Treatment in Wistar Rats Promotes Frequency-Dependent Benefits.Biology · 2025Article
- Disruption of Proteoglycan 4 (PRG4)-CD44 Signaling Modulates Chronic Synovitis in Conditionally Inactivated Mice.Research square · 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
- 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
- Dermal adipogenesis protects against neutrophilic skin inflammation during psoriasis pathogenesis.Cellular & molecular immunology · 2025Article
- [Effect of mechanical stimuli on physicochemical properties of joint fluid in osteoarthritis].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2025Review
- Molecular basis for the calcium-dependent activation of the ribonuclease EndoU.Nature communications · 2025Article
- Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundLubricin/proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. PRG4 has a homeostatic multifaceted role in the joint. PRG4 intra-articular treatment retards progression of cartilage degeneration in pre-clinical posttraumatic osteoarthritis models. The objective of this study is to evaluate the binding of recombinant human PRG4 (rhPRG4) and native human PRG4 (nhPRG4) to toll-like receptors 2 and 4 (TLR2 and TLR4) and whether this interaction underpins a PRG4 anti-inflammatory role in synovial fluid (SF) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA).
methodsrhPRG4 and nhPRG4 binding to TLR2 and TLR4 was evaluated using a direct enzyme linked immunosorbent assay (ELISA). Association of rhPRG4 with TLR2 and TLR4 overexpressing human embryonic kidney (HEK) cells was studied by flow cytometry. Activation of TLR2 and TLR4 on HEK cells by agonists Pam3CSK4 and lipopolysaccharide (LPS) was studied in the absence or presence of nhPRG4 at 50, 100 and 150 μg/ml. Activation of TLR2 and TLR4 by OA SF and RA SF and the effect of nhPRG4 SF treatment on receptor activation was assessed. PRG4 was immunoprecipitated from pooled OA and RA SF. TLR2 and TLR4 activation by pooled OA and RA SF with or without PRG4 immunoprecipitation was compared.
resultsrhPRG4 and nhPRG4 exhibited concentration-dependent binding to TLR2 and TLR4. rhPRG4 associated with TLR2- and TLR4-HEK cells in a time-dependent manner. Co-incubation of nhPRG4 (50, 100 and 150 μg/ml) and Pam3CSK4 or LPS reduced TLR2 or TLR4 activation compared to Pam3CSK4 or LPS alone (p <0.05). OA SF and RA SF activated TLR2 and TLR4 and nhPRG4 treatment reduced SF-induced receptor activation (p <0.001). PRG4 depletion by immunoprecipitation significantly increased TLR2 activation by OA SF and RA SF (p <0.001).
conclusionPRG4 binds to TLR2 and TLR4 and this binding mediates a novel anti-inflammatory role for PRG4.
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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.