ArticleArthritis and rheumatism2013
Suppression of hyaluronan synthesis alleviates inflammatory responses in murine arthritis and in human rheumatoid synovial fibroblasts.
Article in Arthritis and rheumatism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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
44 citing papers in PubMed, 75 citations in OpenAlex.
- Randomised, placebo-controlled trial of oral hymecromone in adults with pulmonary hypertension.Thorax · 2025Trial
- Oral hymecromone decreases hyaluronan in human study participants.The Journal of clinical investigation · 2022Trial
- TScience immunology · 2025Article
- Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection.Matrix biology : journal of the International Society for Matrix Biology · 2023Review
- 4-Methylumbelliferone Targets Revealed by Public Data Analysis and Liver Transcriptome Sequencing.International journal of molecular sciences · 2023Article
- Possible Repositioning of an Oral Anti-Osteoporotic Drug, Ipriflavone, for Treatment of Inflammatory Arthritis via Inhibitory Activity of KIAA1199, a Novel Potent Hyaluronidase.International journal of molecular sciences · 2022Article
- Oral treatment of 4-methylumbelliferone reduced perineuronal nets and improved recognition memory in mice.Brain research bulletin · 2022Article
- Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic Inflammation.Molecules (Basel, Switzerland) · 2022Article
- Article
- Hyaluronan synthesis inhibition impairs antigen presentation and delays transplantation rejection.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- Hyaluronan: Metabolism and Function.Biomolecules · 2020Review
- Inhibitor of Hyaluronic Acid Synthesis 4-Methylumbelliferone as an Anti-Inflammatory Modulator of LPS-Mediated Astrocyte Responses.International journal of molecular sciences · 2020Article
- Estrogen downregulates TAK1 expression in human fibroblast-like synoviocytes and in a rheumatoid arthritis model.Experimental and therapeutic medicine · 2020Article
- 4-Methylumbelliferone suppresses hyaluronan and adipogenesis in primary cultured orbital fibroblasts from Graves' orbitopathy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2020Article
- Suppression of murine osteoarthritis by 4-methylumbelliferone.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2020Article
- Characteristics of Hyaluronan Synthesis Inhibition by 4-Methylumbelliferone in Orbital Fibroblasts.Investigative ophthalmology & visual science · 2020Article
- Hyaluronan levels are increased systemically in human type 2 but not type 1 diabetes independently of glycemic control.Matrix biology : journal of the International Society for Matrix Biology · 2019Article
- 4-Methylumbelliferyl glucuronide contributes to hyaluronan synthesis inhibition.The Journal of biological chemistry · 2019Article
- Hyaluronan in immune dysregulation and autoimmune diseases.Matrix biology : journal of the International Society for Matrix Biology · 2019Review
- Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo clarify the roles of hyaluronan (HA) in joint inflammation and the process of joint destruction, using 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, in a mouse model of collagen-induced arthritis (CIA) and in a monolayer culture of fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis.
methodsDAB/1J mice were immunized with type II collagen. The effects of 4-MU were evaluated by the physiologic arthritis score, paw swelling, the histologic arthritis score, and expression of matrix metalloproteinase 3 (MMP-3) and MMP-13 in chondrocytes and synovial tissue. In vitro, the effect of 4-MU on messenger RNA and protein expression of MMP-1 and MMP-3 was determined. The effects of 4-MU on HA deposition and on serum/medium concentrations of HA were analyzed using biotinylated HA binding protein staining and an HA binding assay, respectively.
resultsTreatment with 4-MU in mice with CIA dramatically decreased the severity of arthritis (based on the arthritis score), paw thickness, and histopathologic changes. MMP-3 and MMP-13 expression in chondrocytes and synovial cells was significantly inhibited by 4-MU in vivo. Treatment with 4-MU also inhibited MMP-1 and MMP-3 expression in tumor necrosis factor α-stimulated FLS, in a dose-dependent manner. The 4-MU-induced decreases in the serum HA concentration in mice with CIA and in "medium" and "pericellular" HA concentrations in cultured FLS support the contention that the inhibitory mechanism of 4-MU is mediated by HA suppression.
conclusionReduced disease activity induced by 4-MU in mice with CIA revealed HA to be a crucial regulator in the course of arthritis. Therefore, 4-MU is a potential therapeutic agent in arthritis, and its inhibitory mechanism is possibly mediated by suppression of HA synthesis.
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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 Socratic graph.