ArticleJournal of orthopaedic surgery and research2021
4-Methylumbelliferone suppresses catabolic activation in anterior cruciate ligament-derived cells via a mechanism independent of hyaluronan inhibition.
Article in Journal of orthopaedic surgery and research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
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Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.
- Coumarins in musculoskeletal health: a systematic review.Frontiers in nutrition · 2026Pooled it
- Hyaluronic acid metabolism and chemotherapy resistance: recent advances and therapeutic potential.Molecular oncology · 2024Review
- Simple virus-free mouse models of COVID-19 pathologies and oral therapeutic intervention.iScience · 2024Article
- 4-Methylumbelliferone Targets Revealed by Public Data Analysis and Liver Transcriptome Sequencing.International journal of molecular sciences · 2023Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe anterior cruciate ligament (ACL) has a key role as a dynamic stabilizer of the knee joints, and ACL dysfunction caused by traumatic or degenerative rupture accelerates osteoarthritis progression. Thus, it is important to prevent the degenerative rupture of the ACL. 4-Methylumbelliferone (4-MU), a pre-approved drug, exerts anti-inflammatory effects in osteoarthritis chondrocytes. It was originally used as an inhibitor of hyaluronan synthesis in chondrocytes.
methodsIn this study, we investigated whether 4-MU affects the expression of catabolic factors, such as matrix metalloproteinase (MMP)-1, MMP-3, and interleukin (IL)-6, in ACL-derived cells and ACL explant cultures using immunohistochemistry, real-time RT-qPCR, and capillary western immunoassay. Furthermore, the hyaluronan concentration was evaluated using a colorimetric assay. Statistical analyses were conducted using analysis of variance for multi-group comparisons, followed by Tukey or Tukey-Kramer post hoc test.
resultsOur results revealed, for the first time, that 4-MU suppressed the IL-β-induced upregulation of pro-catabolic factors, such as MMP-1, MMP-3, and IL-6, in ACL-derived cells. This suppressive effect was also observed in the cultured ligament tissues in ex vivo experiments. 4-MU also reversed an enhanced dependence on glycolysis in IL-1β-activated ACL-derived cells. Furthermore, we found that the suppressive effects of 4-MU were exerted directly and not through the inhibition of hyaluronan synthesis.
conclusionsWe conclude that 4-MU could be an effective and useful treatment for knee osteoarthritis, owing to its anti-inflammatory effect on, not only chondrocytes but also on ligament cells.
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