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Although conventional pharmaceutical therapies aimed to prevent further cartilage loss and joint dysfunction, there are no ideal strategies that target the pathogenesis of OA. Melatonin exhibits a variety of regulatory properties by binding to specific receptors and downstream molecules and exerts a myriad of receptor\u2010independent actions via intracellular targets as a chondrocyte protector, an anti\u2010inflammation modulator, and a free radical scavenger. Melatonin also modulates cartilage regeneration and degradation by directly\/indirectly regulating the expression of main circadian clock genes, such as transcriptional activators [brain and muscle aryl hydrocarbon receptor nuclear translocator\u2010like protein (<jats:italic>Bmal<\/jats:italic>) and circadian locomotor output cycles kaput (<jats:italic>Clock<\/jats:italic>)], transcriptional repressors [period circadian regulator (<jats:italic>Per<\/jats:italic>)1\/2, cryptochrome (<jats:italic>Cry<\/jats:italic>)1\/2, and <jats:italic>Dec<\/jats:italic>2], and nuclear hormone receptors [<jats:italic>Rev\u2010Erbs<\/jats:italic> and retinoid acid\u2010related orphan receptors (<jats:italic>Rors<\/jats:italic>)]. Owing to its effects on cartilage homeostasis, we propose a potential role for melatonin in the prevention and therapy of OA via the modulation of circadian clock genes, mitigation of chondrocyte apoptosis, anti\u2010inflammatory activity, and scavenging of free radicals.<\/jats:p>","DOI":"10.1111\/jpi.12762","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T08:52:28Z","timestamp":1629967948000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The potential remedy of melatonin on osteoarthritis"],"prefix":"10.1111","volume":"71","author":[{"given":"Ko\u2010Hsiu","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Orthopedics Chung Shan Medical University Hospital Taichung Taiwan"},{"name":"School of Medicine Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peace 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