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MicroRNA-140-5p (miR-140) is specifically expressed in cartilage and plays an important role in OA-induced matrix degradation. The aim of this study was to investigate (1) whether intra-articular injection of melatonin could ameliorate surgically induced OA in mice and (2) whether melatonin could regulate matrix-degrading enzymes at the posttranscriptional level by targeting miR-140. In an <jats:italic>in vitro<\/jats:italic> OA environment induced by interleukin-1 beta (IL-1<jats:italic>\u03b2<\/jats:italic>), melatonin treatment improved cell proliferation of human chondrocytes, promoted the expression of cartilage ECM proteins (e.g., type II collagen and aggrecan), and inhibited the levels of IL-1<jats:italic>\u03b2<\/jats:italic>-induced proteinases, such as matrix metalloproteinase 9 (MMP9), MMP13, ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4), and ADAMTS5. Both the microarray and polymerase chain reaction (PCR) experiments revealed that miR-140 was a melatonin-responsive microRNA and melatonin upregulated miR-140 expression, which was suppressed by IL-1<jats:italic>\u03b2<\/jats:italic> stimulation. <jats:italic>In vivo<\/jats:italic> experiments demonstrated that intra-articular injection of melatonin prevented disruptions of cartilage matrix homeostasis and successfully alleviated the progression of surgery-induced OA in mice. Transfection of miR-140 antagomir completely counteracted the antiarthritic effects of melatonin by promoting matrix destruction. Our findings demonstrate that melatonin protects the articular cartilage from OA-induced degradation by targeting miR-140, and intra-articular administration of melatonin may benefit patients suffering from OA.<\/jats:p>","DOI":"10.1155\/2019\/9705929","type":"journal-article","created":{"date-parts":[[2019,12,14]],"date-time":"2019-12-14T18:31:04Z","timestamp":1576348264000},"page":"1-16","source":"Crossref","is-referenced-by-count":41,"title":["Melatonin Prevents Osteoarthritis-Induced Cartilage Degradation via Targeting MicroRNA-140"],"prefix":"10.1155","volume":"2019","author":[{"given":"Yijian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China"},{"name":"Orthopaedic Institute, Medical College, Soochow University, Suzhou 215007, 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