ArticleThe Journal of biological chemistry2016
4-Methylumbelliferone Diminishes Catabolically Activated Articular Chondrocytes and Cartilage Explants via a Mechanism Independent of Hyaluronan Inhibition.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Modulation of lncRNA links endothelial glycocalyx to vascular dysfunction of tyrosine kinase inhibitor.Cardiovascular research · 2023Article
- Downregulation of HAS‑2 regulates the chondrocyte cytoskeleton and induces cartilage degeneration by activating the RhoA/ROCK signaling pathway.International journal of molecular medicine · 2023Article
- 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
- Antitumor effect of 4MU on glioblastoma cells is mediated by senescence induction and CD44, RHAMM and p-ERK modulation.Cell death discovery · 2021Article
- 4-Methylumbelliferone suppresses catabolic activation in anterior cruciate ligament-derived cells via a mechanism independent of hyaluronan inhibition.Journal of orthopaedic surgery and research · 2021Article
- Metabolic reprogramming in chondrocytes to promote mitochondrial respiration reduces downstream features of osteoarthritis.Scientific reports · 2021Article
- Targeting the Tumor Extracellular Matrix by the Natural Molecule 4-Methylumbelliferone: A Complementary and Alternative Cancer Therapeutic Strategy.Frontiers in oncology · 2021Review
- Inhibitor of Hyaluronic Acid Synthesis 4-Methylumbelliferone as an Anti-Inflammatory Modulator of LPS-Mediated Astrocyte Responses.International journal of molecular sciences · 2020Article
- Suppression of murine osteoarthritis by 4-methylumbelliferone.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2020Article
- Chondroprotective effects of 4-methylumbelliferone and hyaluronan synthase-2 overexpression involve changes in chondrocyte energy metabolism.The Journal of biological chemistry · 2019Article
- Hyaluronan synthase 2 (HAS2) overexpression diminishes the procatabolic activity of chondrocytes by a mechanism independent of extracellular hyaluronan.The Journal of biological chemistry · 2019Article
- Simvastatin promotes restoration of chondrocyte morphology and phenotype.Archives of biochemistry and biophysics · 2019Article
- Hematologic and serologic status of military working dogs given standard diet containing natural botanical supplements.Toxicology reports · 2018Article
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5 authors at 1 institution in 1 country.
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Abstract
Depletion of the cartilage proteoglycan aggrecan is one of the earliest events that occurs in association with osteoarthritis. This loss is often accompanied by a coordinate loss in another glycosaminoglycan, hyaluronan. Chondrocytes experimentally depleted of cell-associated hyaluronan respond by switching to a pro-catabolic metabolism that includes enhanced production of endogenous inflammatory mediators and increased synthesis of matrix metalloproteinases. Hyaluronan turnover is also increased. Together, such a response provides for possible establishment of a self-perpetuating spiral of events that maintains or prolongs the pro-catabolic state. Chondrocytes or cartilage can also be activated by treatment with pro-inflammatory cytokines and mediators such as IL-1β, TNFα, LPS, fibronectin fragments, and hyaluronan oligosaccharides. To determine the mechanism of chondrocyte activation due to hyaluronan loss, a depletion method was required that did not include degrading the hyaluronan. In recent years, several laboratories have used the coumarin derivative, 4-methylumbelliferone, as a potent inhibitor of hyaluronan biosynthesis, due in part to its ability to sequester intracellular UDP-glucuronic acid and inhibition of hyaluronan synthase transcription. However, contrary to our expectation, although 4-methylumbelliferone was indeed an inhibitor of hyaluronan biosynthesis, this depletion did not give rise to an activation of chondrocytes or cartilage. Rather, 4-methylumbelliferone directly and selectively blocked gene products associated with the pro-catabolic metabolic state of chondrocytes and did so through a mechanism preceding and independent of hyaluronan inhibition. These data suggest that 4-methylumbelliferone has additional useful applications to block pro-inflammatory cell activation events but complicates how it is used for defining functions related to hyaluronan.
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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.