{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:41:27Z","timestamp":1788968487492,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,12,8]],"date-time":"2019-12-08T00:00:00Z","timestamp":1575763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R21AR072682"],"award-info":[{"award-number":["R21AR072682"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Using in vitro models, we previously reported that 4\u2010methylumbelliferone (4\u2010MU) blocked many of the pro\u2010catabolic features of activated chondrocytes. 4\u2010MU also blocked safranin O loss from human cartilage explants exposed to interleukin 1\u03b2 (IL1\u03b2) in vitro. However, the mechanism for this chondroprotective effect was independent of the action of 4\u2010MU as a hyaluronan (HA) inhibitor. Interestingly, overexpression of HA synthase 2 (HAS2) also blocked the same pro\u2010catabolic features of activated chondrocytes as 4\u2010MU via a mechanism independent of extracellular HA accumulation. Data suggest that altering UDP\u2010sugars may be behind these changes in chondrocyte metabolism. However, all of our previous experiments with 4\u2010MU or HAS2 overexpression were performed in vitro. The purpose of this study was to confirm whether 4\u2010MU was effective at limiting the effects of osteoarthritis (OA) on articular cartilage in vivo. The progression of OA was evaluated after destabilization of the medial meniscus (DMM) surgery on C57BL\/6 mice in the presence or absence of 4\u2010MU\u2010containing chow. Mice fed 4\u2010MU after DMM surgery exhibited significant suppression of OA starting from an early stage in vivo. Mice fed 4\u2010MU exhibited lower OARSI scores after DMM; reduced osteophyte formation and reduced MMP3 and MMP13 immunostaining. 4\u2010MU also exerted pronounced chondroprotective effects on murine joint cartilage exposed to IL1\u03b2 in vitro and, blocked IL1\u03b2\u2010enhanced lactate production in cartilage explants. Therefore, 4\u2010MU is effective at significantly reducing the loss of proteoglycan and reducing MMP production both in vitro and in vivo as well as cartilage damage and osteophyte formation in vivo after DMM. \u00a9 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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