ArticlePloS one2019
Prg4 prevents osteoarthritis induced by dominant-negative interference of TGF-ß signaling in mice.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Lubricin in experimental and naturally occurring osteoarthritis: a systematic review.Osteoarthritis and cartilage · 2020Pooled it
- Structural and functional changes in articulating joints during aging of male and female C57BL/6JN mice.Osteoarthritis and cartilage · 2026Article
- Development of a deep learning-based grid walking test for assessing post-stroke motor function in mice.Frontiers in behavioral neuroscience · 2026Article
- Platelet-rich plasma in cartilage repair: biological mechanisms and clinical perspectives.Frontiers in sports and active living · 2026Review
- Bioinformatic identification of important roles of COL1A1 and TNFRSF12A in cartilage injury and osteoporosis.Journal of the International Society of Sports Nutrition · 2025Article
- Inhibition of Phlpp1 preserves the mechanical integrity of articular cartilage in a murine model of post-traumatic osteoarthritis.Osteoarthritis and cartilage · 2024Article
- Interactions and Trends of Interleukins, PAI-1, CRP, and TNF-α in Inflammatory Responses during the Perioperative Period of Joint Arthroplasty: Implications for Pain Management-A Narrative Review.Journal of personalized medicine · 2024Review
- Proteoglycan 4 (PRG4) treatment enhances wound closure and tissue regeneration.NPJ Regenerative medicine · 2022Article
- Primary Cilia Direct Murine Articular Cartilage Tidemark Patterning Through Hedgehog Signaling and Ambulatory Load.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Regulatory Mechanisms ofInternational journal of molecular sciences · 2022Review
- Proteoglycans in Cancer: Friends or Enemies? A Special Focus on Hepatocellular Carcinoma.Cancers · 2022Review
- Gene therapy approaches for equine osteoarthritis.Frontiers in veterinary science · 2022Review
- Molecular mechanisms of mechanical load-induced osteoarthritis.International orthopaedics · 2021Review
- Micellar Casein and Whey Powder Hold a TGF-β Activity and Regulate ID Genes In Vitro.Molecules (Basel, Switzerland) · 2021Article
- Experimental Therapeutics for the Treatment of Osteoarthritis.Journal of experimental pharmacology · 2021Review
- BMSC-Derived Exosomes Ameliorate Osteoarthritis by Inhibiting Pyroptosis of Cartilage via Delivering miR-326 Targeting HDAC3 and STAT1//NF-Mediators of inflammation · 2021Article
- Proteoglycan-4 is correlated with longer survival in HCC patients and enhances sorafenib and regorafenib effectiveness via CD44 in vitro.Cell death & disease · 2020Article
- The Damage-Associated Molecular Patterns (DAMPs) as Potential Targets to Treat Osteoarthritis: Perspectives From a Review of the Literature.Frontiers in medicine · 2020Review
- Scaffoldless tissue-engineered cartilage for studying transforming growth factor beta-mediated cartilage formation.Biotechnology progress · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectivePrg4, also known as Lubricin, acts as a joint/boundary lubricant. Prg4 has been used to prevent surgically induced osteoarthritis (OA) in mice. Surgically induced OA serves as a good model for post-traumatic OA but is not ideal for recapitulating age-related OA. Reduced expression of the TGF-β type II receptor (TGFβR2) is associated with age-related OA in clinical samples, so we previously characterized a mouse model that exhibits OA due to expression of a mutated dominant-negative form of TGFβR2 (DNIIR). Prg4 expression was significantly reduced in DNIIR mice. Furthermore, we showed that Prg4 was a transcriptional target of TGF-ß via activation of Smad3, the main signal transducing protein for TGF-ß. The objective of the present study was to determine whether maintenance of Prg4, a down-stream transcriptional target of TGF-ß, prevents OA associated with attenuated TGF-ß signaling in mice.
designWild-type, DNIIR, and bitransgenic mice that express both DNIIR and Prg4, were compared. Mice were assessed with a foot misplacement behavioral test, μCT, histology, and Western blot.
resultsCompared to DNIIR mice, bitransgenic DNIIR+Prg4 mice missed 1.3 (0.4, 2.1) fewer steps while walking (mean difference (95% confidence interval)), exhibited a cartilage fibrillation score that was 1.8 (0.4, 3.1) points lower, exhibited cartilage that was 28.2 (0.5, 55.9) μm thicker, and exhibited an OARSI score that was 6.8 (-0.9, 14.5) points lower. However, maintenance of Prg4 expression did not restore levels of phosphorylated Smad3 in DNIIR mice, indicating Prg4 does not simply stimulate TGF-ß signaling.
conclusionsOur results indicate that maintenance of Prg4 expression prevents OA progression associated with reduced TGF-β signaling in mice. Since there was no evidence that Prg4 acts by stimulating the TGF-ß signaling cascade, we propose that Prg4, a transcriptional target of TGF-ß, attenuates OA progression through its joint lubrication function.
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