{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:57:29Z","timestamp":1791583049578,"version":"4.3.4"},"reference-count":115,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T00:00:00Z","timestamp":1664841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Osteoarthritis (OA) is a slowly progressing and irreversible joint disease. The existing non-surgical treatment can only delay its progress, making the early treatment of OA a research hotspot in recent years. Melatonin, a neurohormone mainly secreted by the pineal gland, has a variety of regulatory functions in different organs, and numerous studies have confirmed its therapeutic effect on OA. Non-coding RNAs (ncRNAs) constitute the majority of the human transcribed genome. Various ncRNAs show significant differentially expressed between healthy people and OA patients. ncRNAs play diverse roles in many cellular processes and have been implicated in many pathological conditions, especially OA. Interestingly, the latest research found a close interaction between ncRNAs and melatonin in regulating the pathogenesis of OA. This review discusses the current understanding of the melatonin-mediated modulation of ncRNAs in the early stage of OA. We also delineate the potential link between rhythm genes and ncRNAs in chondrocytes. This review will serve as a solid foundation to formulate ideas for future mechanistic studies on the therapeutic potential of melatonin and ncRNAs in OA and better explore the emerging functions of the ncRNAs.<\/jats:p>","DOI":"10.3389\/fgene.2022.968919","type":"journal-article","created":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T04:58:01Z","timestamp":1664859481000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["The therapeutic effect and mechanism of melatonin on osteoarthritis: From the perspective of non-coding RNAs"],"prefix":"10.3389","volume":"13","author":[{"given":"Shuai","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"105839","DOI":"10.1016\/j.phrs.2021.105839","article-title":"Melatonin as a promising modulator of aging related neurodegenerative disorders: Role of microRNAs","volume":"173","author":"Alamdari","year":"2021","journal-title":"Pharmacol. Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"BSR20191908","DOI":"10.1042\/BSR20191908","article-title":"miR-122\/SIRT1 axis regulates chondrocyte extracellular matrix degradation in osteoarthritis","volume":"40","author":"Bai","year":"2020","journal-title":"Biosci. Rep."},{"key":"B3","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1007\/s00296-010-1641-9","article-title":"Melatonin attenuates clock gene cryptochrome1, which may aggravate mouse anti-type II collagen antibody-induced arthritis","volume":"32","author":"Bang","year":"2012","journal-title":"Rheumatol. Int."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1136\/ard.61.12.1075","article-title":"Rhythmic variations in pain, stiffness, and manual dexterity in hand osteoarthritis","volume":"61","author":"Bellamy","year":"2002","journal-title":"Ann. Rheum. Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/nrrheum.2010.213","article-title":"The role of mitochondria in osteoarthritis","volume":"7","author":"Blanco","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"5282","DOI":"10.1096\/fj.201902692R","article-title":"Melatonin alleviates cardiac fibrosis via inhibiting lncRNA MALAT1\/miR-141-mediated NLRP3 inflammasome and TGF-\u03b21\/Smads signaling in diabetic cardiomyopathy","volume":"34","author":"Che","year":"2020","journal-title":"FASEB J."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1274S","DOI":"10.1177\/1947603519855759","article-title":"LncRNA MEG3 inhibits the degradation of the extracellular matrix of chondrocytes in osteoarthritis via targeting miR-93\/TGFBR2 Axis","volume":"13","author":"Chen","year":"","journal-title":"Cartilage"},{"key":"B8","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.neuroscience.2020.06.026","article-title":"Melatonin promotes neuroprotection of H2O2-induced neural stem cells via lncRNA MEG3\/miRNA-27a-3p\/MAP2K4 axis","volume":"446","author":"Chen","year":"2020","journal-title":"Neuroscience"},{"key":"B9","doi-asserted-by":"publisher","first-page":"101910","DOI":"10.1016\/j.redox.2021.101910","article-title":"The lncRNA Malat1 regulates microvascular function after myocardial infarction in mice via miR-26b-5p\/Mfn1 axis-mediated mitochondrial dynamics","volume":"41","author":"Chen","year":"","journal-title":"Redox Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1041s","DOI":"10.1177\/19476035211038748","article-title":"Anti-apoptosis and autophagy effects of melatonin protect rat chondrocytes against oxidative stress via regulation of AMPK\/Foxo3 pathways","volume":"13","author":"Chen","year":"","journal-title":"Cartilage"},{"key":"B11","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1210\/er.2018-00084","article-title":"Melatonin as a hormone: New physiological and clinical insights","volume":"39","author":"Cipolla-Neto","year":"2018","journal-title":"Endocr. Rev."},{"key":"B12","doi-asserted-by":"publisher","first-page":"25312","DOI":"10.1074\/jbc.M112.356733","article-title":"MicroRNAs in the pineal gland: miR-483 regulates melatonin synthesis by targeting arylalkylamine N-acetyltransferase","volume":"287","author":"Clokie","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B13","doi-asserted-by":"publisher","first-page":"E398","DOI":"10.3390\/cells9020398","article-title":"Differential regulation of circRNA, miRNA, and piRNA during early osteogenic and chondrogenic differentiation of human mesenchymal stromal cells","volume":"9","author":"Della Bella","year":"2020","journal-title":"Cells"},{"key":"B14","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1186\/s13018-021-02738-2","article-title":"Circ_0045714\/miR-331-3p interaction affects IL-1\u03b2-evoked human articular chondrocyte injury through regulating PIK3R3 in a ceRNA regulatory cascade","volume":"16","author":"Ding","year":"2021","journal-title":"J. Orthop. Surg. Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1172\/JCI82755","article-title":"The chondrocyte clock gene Bmal1 controls cartilage homeostasis and integrity","volume":"126","author":"Dudek","year":"2016","journal-title":"J. Clin. Invest."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e22727","DOI":"10.1371\/journal.pone.0022727","article-title":"piR_015520 belongs to Piwi-associated RNAs regulates expression of the human melatonin receptor 1A gene","volume":"6","author":"Esposito","year":"2011","journal-title":"PLoS One"},{"key":"B17","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1530\/JOE-19-0022","article-title":"Circadian production of melatonin in cartilage modifies rhythmic gene expression","volume":"241","author":"Fu","year":"2019","journal-title":"J. Endocrinol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/s13287-018-0892-3","article-title":"Melatonin rescued interleukin 1\u03b2-impaired chondrogenesis of human mesenchymal stem cells","volume":"9","author":"Gao","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"B19","doi-asserted-by":"publisher","first-page":"17167","DOI":"10.1002\/jcb.28977","article-title":"Long noncoding RNA MALAT-1 inhibits apoptosis and matrix metabolism disorder in interleukin-1\u03b2-induced inflammation in articular chondrocytes via the JNK signaling pathway","volume":"120","author":"Gao","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e12752","DOI":"10.1111\/acel.12752","article-title":"Evidence that miR-146a attenuates aging- and trauma-induced osteoarthritis by inhibiting Notch1, IL-6, and IL-1 mediated catabolism","volume":"17","author":"Guan","year":"2018","journal-title":"Aging Cell"},{"key":"B21","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.matbio.2018.05.008","article-title":"Osteoarthritis as a disease of the cartilage pericellular matrix","author":"Guilak","year":"2018","journal-title":"Matrix Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1016\/j.joca.2015.02.020","article-title":"Catabolic cytokines disrupt the circadian clock and the expression of clock-controlled genes in cartilage via an NF\u043aB-dependent pathway","volume":"23","author":"Guo","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"B23","doi-asserted-by":"publisher","first-page":"55967","DOI":"10.18632\/oncotarget.18356","article-title":"Melatonin inhibits Sirt1-dependent NAMPT and NFAT5 signaling in chondrocytes to attenuate osteoarthritis","volume":"8","author":"Guo","year":"2017","journal-title":"Oncotarget"},{"key":"B24","doi-asserted-by":"publisher","first-page":"R122","DOI":"10.1186\/ar3852","article-title":"Disruption of rhythms of molecular clocks in primary synovial fibroblasts of patients with osteoarthritis and rheumatoid arthritis, role of IL-1\u03b2\/TNF","volume":"14","author":"Haas","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"B25","doi-asserted-by":"publisher","first-page":"621","DOI":"10.2147\/CIA.S193765","article-title":"Melatonin benefits to the growth of human annulus fibrosus cells through inhibiting miR-106a-5p\/ATG7 signaling pathway","volume":"14","author":"Hai","year":"2019","journal-title":"Clin. Interv. Aging"},{"key":"B26","doi-asserted-by":"publisher","first-page":"18257","DOI":"10.18632\/aging.203267","article-title":"The lncRNA H19\/miR-541-3p\/Wnt\/\u03b2-catenin axis plays a vital role in melatonin-mediated osteogenic differentiation of bone marrow mesenchymal stem cells","volume":"13","author":"Han","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"B27","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1002\/cbf.3613","article-title":"Melatonin alleviates d-galactose-decreased hyaluronic acid production in synovial membrane cells via Sirt1 signalling","volume":"39","author":"Han","year":"","journal-title":"Cell biochem. Funct."},{"key":"B28","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.bbrc.2020.02.090","article-title":"Melatonin suppresses ischemia-induced fibrosis by regulating miR-149","volume":"525","author":"Han","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B29","doi-asserted-by":"publisher","first-page":"E1223","DOI":"10.3390\/ijms20051223","article-title":"Aging, melatonin, and the pro- and anti-inflammatory networks","volume":"20","author":"Hardeland","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B30","first-page":"194","article-title":"Melatonin in aging and disease -multiple consequences of reduced secretion, options and limits of treatment","volume":"3","author":"Hardeland","year":"2012","journal-title":"Aging Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"18221","DOI":"10.3390\/ijms151018221","article-title":"Melatonin, noncoding RNAs, messenger RNA stability and epigenetics--evidence, hints, gaps and perspectives","volume":"15","author":"Hardeland","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.4049\/jimmunol.0903284","article-title":"Mammalian clock gene Cryptochrome regulates arthritis via proinflammatory cytokine TNF-alpha","volume":"184","author":"Hashiramoto","year":"2010","journal-title":"J. Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"5406284","DOI":"10.1155\/2020\/5406284","article-title":"Melatonin antagonizes nickel-induced aerobic glycolysis by blocking ROS-mediated HIF-1\u03b1\/miR210\/ISCU Axis Activation","volume":"2020","author":"He","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1621394","DOI":"10.1155\/2020\/1621394","article-title":"Exosome and melatonin additively attenuates inflammation by transferring miR-34a, miR-124, and miR-135b","volume":"2020","author":"Heo","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"B35","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.jss.2010.08.036","article-title":"Melatonin impairs fracture healing by suppressing RANKL-mediated bone remodeling","volume":"173","author":"Histing","year":"2012","journal-title":"J. Surg. Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"97633","DOI":"10.18632\/oncotarget.19276","article-title":"Role of melatonin combined with exercise as a switch-like regulator for circadian behavior in advanced osteoarthritic knee","volume":"8","author":"Hong","year":"2017","journal-title":"Oncotarget"},{"key":"B37","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/jpi.12143","article-title":"Salutary effects of melatonin combined with treadmill exercise on cartilage damage","volume":"57","author":"Hong","year":"2014","journal-title":"J. Pineal Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"E1415","DOI":"10.3390\/jcm8091415","article-title":"Physiological and pathological role of circadian hormones in osteoarthritis: Dose-dependent or time-dependent?","volume":"8","author":"Hossain","year":"2019","journal-title":"J. Clin. Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1111\/jpi.12362","article-title":"Apoptosis signaling pathways in osteoarthritis and possible protective role of melatonin","volume":"61","author":"Hosseinzadeh","year":"2016","journal-title":"J. Pineal Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"617654","DOI":"10.3389\/fphys.2021.617654","article-title":"LncRNA MEG3 protects chondrocytes from IL-1\u03b2-induced inflammation via regulating miR-9-5p\/KLF4 Axis","volume":"12","author":"Huang","year":"2021","journal-title":"Front. Physiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1016\/S0140-6736(20)32230-3","article-title":"Osteoarthritis in 2020 and beyond: A lancet commission","volume":"396","author":"Hunter","year":"2020","journal-title":"Lancet"},{"key":"B43","doi-asserted-by":"publisher","first-page":"3230","DOI":"10.1111\/bph.13898","article-title":"Melatonin in regulation of inflammatory pathways in rheumatoid arthritis and osteoarthritis: Involvement of circadian clock genes","volume":"175","author":"Jahanban-Esfahlan","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s10863-020-09868-y","article-title":"Circ_0045714 alleviates TNF-\u03b1-induced chondrocyte injury and extracellular matrix degradation through miR-218-5p\/HRAS axis","volume":"53","author":"Jiang","year":"","journal-title":"J. Bioenerg. Biomembr."},{"key":"B45","first-page":"8728","article-title":"miR-590-5p affects chondrocyte proliferation, apoptosis, and inflammation by targeting FGF18 in osteoarthritis","volume":"13","author":"Jiang","year":"","journal-title":"Am. J. Transl. Res."},{"key":"B46","volume-title":"Kidney transplantation and cardiovascular events among patients with end-stage renal disease due to lupus nephritis","author":"Jorge","year":"2021"},{"key":"B47","doi-asserted-by":"publisher","first-page":"e373","DOI":"10.1038\/mtna.2016.64","article-title":"microRNA-140 inhibits inflammation and stimulates chondrogenesis in a model of interleukin 1\u03b2-induced osteoarthritis","volume":"5","author":"Karlsen","year":"2016","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"B48","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/s13059-015-0676-3","article-title":"The ADAMTS (A disintegrin and metalloproteinase with thrombospondin motifs) family","volume":"16","author":"Kelwick","year":"2015","journal-title":"Genome Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1038\/s41588-018-0252-3","article-title":"Long noncoding RNA MALAT1 suppresses breast cancer metastasis","volume":"50","author":"Kim","year":"2018","journal-title":"Nat. Genet."},{"key":"B50","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/s13577-017-0177-7","article-title":"Hsa_circ_0045714 regulates chondrocyte proliferation, apoptosis and extracellular matrix synthesis by promoting the expression of miR-193b target gene IGF1R","volume":"30","author":"Li","year":"2017","journal-title":"Hum. Cell"},{"key":"B51","doi-asserted-by":"publisher","first-page":"116801","DOI":"10.1016\/j.lfs.2019.116801","article-title":"LncRNA MALAT1 mediates proliferation of LPS treated-articular chondrocytes by targeting the miR-146a-PI3K\/Akt\/mTOR axis","volume":"254","author":"Li","year":"2020","journal-title":"Life Sci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"3856","DOI":"10.3892\/etm.2018.5918","article-title":"Methylene blue relieves the development of osteoarthritis by upregulating lncRNA MEG3","volume":"15","author":"Li","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s13075-016-0997-y","article-title":"E2 regulates MMP-13 via targeting miR-140 in IL-1\u03b2-induced extracellular matrix degradation in human chondrocytes","volume":"18","author":"Liang","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"B54","doi-asserted-by":"publisher","first-page":"36938","DOI":"10.1021\/acsami.0c10458","article-title":"Chondrocyte-Targeted MicroRNA delivery by engineered exosomes toward a cell-free osteoarthritis therapy","volume":"12","author":"Liang","year":"2020","journal-title":"ACS Appl. Mat. Interfaces"},{"key":"B55","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1111\/j.1600-079X.2012.00991.x","article-title":"Cytoprotective and anti-inflammatory effects of melatonin in hydrogen peroxide-stimulated CHON-001 human chondrocyte cell line and rabbit model of osteoarthritis via the SIRT1 pathway","volume":"53","author":"Lim","year":"2012","journal-title":"J. Pineal Res."},{"key":"B56","doi-asserted-by":"publisher","first-page":"11326","DOI":"10.1074\/jbc.M807709200","article-title":"miR-199a, a bone morphogenic protein 2-responsive MicroRNA, regulates chondrogenesis via direct targeting to Smad1","volume":"284","author":"Lin","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.3349\/ymj.2019.60.11.1081","article-title":"LncRNA MALAT1\/MiR-145 adjusts IL-1\u03b2-induced chondrocytes viability and cartilage matrix degradation by regulating ADAMTS5 in human osteoarthritis","volume":"60","author":"Liu","year":"2019","journal-title":"Yonsei Med. J."},{"key":"B58","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/s41419-022-04656-5","article-title":"Melatonin abolished proinflammatory factor expression and antagonized osteoarthritis progression in vivo","volume":"13","author":"Liu","year":"2022","journal-title":"Cell Death Dis."},{"key":"B59","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.freeradbiomed.2013.12.012","article-title":"Rescue of proinflammatory cytokine-inhibited chondrogenesis by the antiarthritic effect of melatonin in synovium mesenchymal stem cells via suppression of reactive oxygen species and matrix metalloproteinases","volume":"68","author":"Liu","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"e12762","DOI":"10.1111\/jpi.12762","article-title":"The potential remedy of melatonin on osteoarthritis","volume":"71","author":"Lu","year":"","journal-title":"J. Pineal Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3892\/ijmm.2021.4915","article-title":"Insight into the roles of melatonin in bone tissue and bone-related diseases (Review)","volume":"47","author":"Lu","year":"","journal-title":"Int. J. Mol. Med."},{"key":"B62","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1097\/MAT.0000000000000688","article-title":"New approach for differentiation of bone marrow mesenchymal stem cells toward chondrocyte cells with overexpression of MicroRNA-140","volume":"64","author":"Mahboudi","year":"2018","journal-title":"Asaio J."},{"key":"B63","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.arr.2018.04.003","article-title":"The multiple functions of melatonin in regenerative medicine","volume":"45","author":"Majidinia","year":"2018","journal-title":"Ageing Res. Rev."},{"key":"B64","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/nrd.2016.117","article-title":"Non-coding RNAs as drug targets","volume":"16","author":"Matsui","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"B65","doi-asserted-by":"publisher","first-page":"2723","DOI":"10.1002\/art.24745","article-title":"MicroRNA-140 is expressed in differentiated human articular chondrocytes and modulates interleukin-1 responses","volume":"60","author":"Miyaki","year":"2009","journal-title":"Arthritis Rheum."},{"key":"B66","doi-asserted-by":"publisher","first-page":"20532","DOI":"10.18632\/oncotarget.7978","article-title":"Multitargeting activity of miR-24 inhibits long-term melatonin anticancer effects","volume":"7","author":"Mori","year":"2016","journal-title":"Oncotarget"},{"key":"B67","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.semarthrit.2019.03.008","article-title":"The CNS theory of osteoarthritis: Opportunities beyond the joint","volume":"49","author":"Morris","year":"2019","journal-title":"Semin. Arthritis Rheum."},{"key":"B68","doi-asserted-by":"publisher","first-page":"638","DOI":"10.3858\/emm.2009.41.9.070","article-title":"Comprehensive analysis of microRNA-mRNA co-expression in circadian rhythm","volume":"41","author":"Na","year":"2009","journal-title":"Exp. Mol. Med."},{"key":"B69","doi-asserted-by":"publisher","first-page":"2194","DOI":"10.1002\/jcp.30006","article-title":"Cartilage regeneration with dual-drug-releasing injectable hydrogel\/microparticle system: In vitro and in vivo study","volume":"236","author":"Naghizadeh","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.rdc.2012.10.004","article-title":"Epidemiology of osteoarthritis","volume":"39","author":"Neogi","year":"2013","journal-title":"Rheum. Dis. Clin. North Am."},{"key":"B71","doi-asserted-by":"publisher","first-page":"e1471","DOI":"10.1002\/wrna.1471","article-title":"Cytoplasmic functions of long noncoding RNAs","volume":"9","author":"Noh","year":"2018","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"B72","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1111\/j.1600-079X.2008.00646.x","article-title":"Melatonin enhances cartilage matrix synthesis by porcine articular chondrocytes","volume":"46","author":"Pei","year":"2009","journal-title":"J. Pineal Res."},{"key":"B73","doi-asserted-by":"publisher","first-page":"10855","DOI":"10.1111\/jcmm.15714","article-title":"Curcumin reinforces MSC-derived exosomes in attenuating osteoarthritis via modulating the miR-124\/NF-kB and miR-143\/ROCK1\/TLR9 signalling pathways","volume":"24","author":"Qiu","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"B74","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.joca.2021.10.003","article-title":"Osteoarthritis year in review 2021: Epidemiology & therapy","volume":"30","author":"Quicke","year":"2022","journal-title":"Osteoarthr. Cartil."},{"key":"B75","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/S0079-6123(08)81008-4","article-title":"Melatonin: A multitasking molecule","volume":"181","author":"Reiter","year":"2010","journal-title":"Prog. Brain Res."},{"key":"B76","doi-asserted-by":"publisher","first-page":"524","DOI":"10.3390\/antiox10040524","article-title":"The impact of melatonin and NLRP3 inflammasome on the expression of microRNAs in aged muscle","volume":"10","author":"Sayed","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"B77","doi-asserted-by":"publisher","first-page":"896206","DOI":"10.1155\/2014\/896206","article-title":"Competing endogenous RNA: The key to posttranscriptional regulation","volume":"2014","author":"Sen","year":"2014","journal-title":"ScientificWorldJournal."},{"key":"B78","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1007\/s00011-020-01346-w","article-title":"MiR-146a-5p promotes IL-1\u03b2-induced chondrocyte apoptosis through the TRAF6-mediated NF-kB pathway","volume":"69","author":"Shao","year":"2020","journal-title":"Inflamm. Res."},{"key":"B79","doi-asserted-by":"publisher","first-page":"650","DOI":"10.7507\/1002-1892.201806060","article-title":"Effects of cartilage progenitor cells and microRNA-140 on repair of osteoarthritic cartilage injury","volume":"33","author":"Si","year":"2019","journal-title":"Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi"},{"key":"B80","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5604\/01.3001.0013.0135","article-title":"miRNA-146a-5p is upregulated in serum and cartilage samples of patients with osteoarthritis","volume":"91","author":"Skrzypa","year":"2019","journal-title":"Pol. Przegl. Chir."},{"key":"B81","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/j.1600-079X.2010.00812.x","article-title":"Matrix metalloproteinases in health and disease: Regulation by melatonin","volume":"50","author":"Swarnakar","year":"2011","journal-title":"J. Pineal Res."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1498","DOI":"10.1007\/s10753-020-01227-8","article-title":"The fibroblast-like synoviocyte derived exosomal long non-coding RNA H19 alleviates osteoarthritis progression through the miR-106b-5p\/TIMP2 Axis","volume":"43","author":"Tan","year":"2020","journal-title":"Inflammation"},{"key":"B83","doi-asserted-by":"publisher","first-page":"4455","DOI":"10.1016\/j.bioactmat.2021.04.031","article-title":"Small extracellular vesicles in combination with sleep-related circRNA3503: A targeted therapeutic agent with injectable thermosensitive hydrogel to prevent osteoarthritis","volume":"6","author":"Tao","year":"2021","journal-title":"Bioact. Mat."},{"key":"B84","doi-asserted-by":"publisher","first-page":"R197","DOI":"10.1186\/ar4387","article-title":"NFAT3 and TGF-\u03b2\/SMAD3 regulate the expression of miR-140 in osteoarthritis","volume":"15","author":"Tardif","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"B85","doi-asserted-by":"publisher","first-page":"633","DOI":"10.3892\/ijmm.2020.4820","article-title":"Melatonin inhibits RANKL-induced osteoclastogenesis through the miR-882\/Rev-erb\u03b1 axis in Raw264.7 cells","volume":"47","author":"Tian","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"B86","doi-asserted-by":"publisher","first-page":"111274","DOI":"10.1016\/j.biopha.2021.111274","article-title":"Melatonin attenuates oxidative stress and inflammation of Muller cells in diabetic retinopathy via activating the Sirt1 pathway","volume":"137","author":"Tu","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"B87","doi-asserted-by":"publisher","first-page":"3507","DOI":"10.1002\/jcb.23298","article-title":"ADAMTS-4 and ADAMTS-5: Key enzymes in osteoarthritis","volume":"112","author":"Verma","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"B88","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.jpainsymman.2012.08.019","article-title":"Analgesic and sedative effects of melatonin in temporomandibular disorders: A double-blind, randomized, parallel-group, placebo-controlled study","volume":"46","author":"Vidor","year":"2013","journal-title":"J. Pain Symptom Manage."},{"key":"B89","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/jpi.12189","article-title":"Melatonin feedback on clock genes: A theory involving the proteasome","volume":"58","author":"Vriend","year":"2015","journal-title":"J. Pineal Res."},{"key":"B90","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.bbrc.2020.05.180","article-title":"The long noncoding RNA H19 attenuates force-driven cartilage degeneration via miR-483-5p\/Dusp5","volume":"529","author":"Wang","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B91","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1038\/s41467-021-21049-y","article-title":"Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups","volume":"12","author":"Wang","year":"","journal-title":"Nat. Commun."},{"key":"B92","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1002\/acr.24151","article-title":"Knee osteoarthritis, potential mediators, and risk of all-cause mortality: Data from the osteoarthritis initiative","volume":"73","author":"Wang","year":"","journal-title":"Arthritis Care Res. Hob."},{"key":"B93","doi-asserted-by":"publisher","first-page":"255","DOI":"10.2174\/1566523219666190716092203","article-title":"The therapeutic potential and role of miRNA, lncRNA, and circRNA in osteoarthritis","volume":"19","author":"Wu","year":"2019","journal-title":"Curr. Gene Ther."},{"key":"B94","doi-asserted-by":"publisher","first-page":"e12483","DOI":"10.1111\/jpi.12483","article-title":"Melatonin-mediated miR-526b-3p and miR-590-5p upregulation promotes chondrogenic differentiation of human mesenchymal stem cells","volume":"65","author":"Wu","year":"2018","journal-title":"J. Pineal Res."},{"key":"B95","doi-asserted-by":"publisher","first-page":"297","DOI":"10.14336\/AD.2020.0519","article-title":"Melatonin: Effects on cartilage homeostasis and therapeutic prospects in cartilage-related diseases","volume":"12","author":"Xie","year":"2021","journal-title":"Aging Dis."},{"key":"B96","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s13578-017-0195-x","article-title":"The lncRNA MEG3 downregulation leads to osteoarthritis progression via miR-16\/SMAD7 axis","volume":"7","author":"Xu","year":"2017","journal-title":"Cell Biosci."},{"key":"B97","doi-asserted-by":"publisher","first-page":"4235","DOI":"10.1080\/21655979.2022.2027175","article-title":"Melatonin affects hypoxia-inducible factor 1\u03b1 and ameliorates delayed brain injury following subarachnoid hemorrhage via H19\/miR-675\/HIF1A\/TLR4","volume":"13","author":"Xu","year":"2022","journal-title":"Bioengineered"},{"key":"B98","doi-asserted-by":"publisher","first-page":"3096","DOI":"10.1210\/en.2015-2042","article-title":"Clock gene Bmal1 modulates human cartilage gene expression by crosstalk with Sirt1","volume":"157","author":"Yang","year":"2016","journal-title":"Endocrinology"},{"key":"B99","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.steroids.2017.08.005","article-title":"Melatonin protects chondrocytes from impairment induced by glucocorticoids via NAD(+)-dependent SIRT1","volume":"126","author":"Yang","year":"2017","journal-title":"Steroids"},{"key":"B100","doi-asserted-by":"publisher","first-page":"109379","DOI":"10.1016\/j.cellsig.2019.109379","article-title":"Long non-coding RNA MEG3 inhibits chondrogenic differentiation of synovium-derived mesenchymal stem cells by epigenetically inhibiting TRIB2 via methyltransferase EZH2","volume":"63","author":"You","year":"2019","journal-title":"Cell. Signal."},{"key":"B101","doi-asserted-by":"publisher","first-page":"2343","DOI":"10.3892\/etm.2020.8471","article-title":"Therapeutic effect of Resveratrol in the treatment of osteoarthritis via the MALAT1\/miR-9\/NF-\u03baB signaling pathway","volume":"19","author":"Zhang","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"B102","doi-asserted-by":"publisher","first-page":"52179","DOI":"10.18632\/oncotarget.10538","article-title":"Melatonin suppresses autophagy in type 2 diabetic osteoporosis","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"B103","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1007\/s12038-019-9943-x","article-title":"Long non-coding RNA H19 modulates proliferation and apoptosis in osteoarthritis via regulating miR-106a-5p","volume":"44","author":"Zhang","year":"","journal-title":"J. Biosci."},{"key":"B104","doi-asserted-by":"publisher","first-page":"e2734","DOI":"10.1038\/cddis.2017.146","article-title":"miR-146a facilitates osteoarthritis by regulating cartilage homeostasis via targeting Camk2d and Ppp3r2","volume":"8","author":"Zhang","year":"2017","journal-title":"Cell Death Dis."},{"key":"B105","doi-asserted-by":"publisher","first-page":"10499","DOI":"10.18632\/aging.102472","article-title":"Melatonin modulates IL-1\u03b2-induced extracellular matrix remodeling in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration and inflammation","volume":"11","author":"Zhang","year":"","journal-title":"Agingy NY)"},{"key":"B106","doi-asserted-by":"publisher","first-page":"9705929","DOI":"10.1155\/2019\/9705929","article-title":"Melatonin prevents osteoarthritis-induced cartilage degradation via targeting MicroRNA-140","volume":"2019","author":"Zhang","year":"","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B107","doi-asserted-by":"publisher","first-page":"e12449","DOI":"10.1111\/jpi.12449","article-title":"Melatonin prevents endothelial cell pyroptosis via regulation of long noncoding RNA MEG3\/miR-223\/NLRP3 axis","volume":"64","author":"Zhang","year":"2018","journal-title":"J. Pineal Res."},{"key":"B108","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s13578-019-0302-2","article-title":"LncRNA MALAT1 promotes osteoarthritis by modulating miR-150-5p\/AKT3 axis","volume":"9","author":"Zhang","year":"","journal-title":"Cell Biosci."},{"key":"B109","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.3892\/mmr.2020.10982","article-title":"Exosomes from adipose-derived stem cells promote chondrogenesis and suppress inflammation by upregulating miR-145 and miR-221","volume":"21","author":"Zhao","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"B110","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/nature14878","article-title":"Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture","volume":"526","author":"Zheng","year":"2015","journal-title":"Nature"},{"key":"B111","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.7150\/ijms.51743","article-title":"Identifying daily changes in circRNAs and circRNA-associated-ceRNA networks in the rat pineal gland","volume":"18","author":"Zheng","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"B112","doi-asserted-by":"publisher","first-page":"bqab255","DOI":"10.1210\/endocr\/bqab255","article-title":"CircRNA-WNK2 acts as a ceRNA for miR-328a-3p to promote AANAT expression in the male rat pineal gland","volume":"163","author":"Zheng","year":"2022","journal-title":"Endocrinology"},{"key":"B113","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.18502\/ijph.v49i8.3893","article-title":"The expression and diagnostic value of LncRNA H19 in the blood of patients with osteoarthritis","volume":"49","author":"Zhou","year":"2020","journal-title":"Iran. J. Public Health"},{"key":"B114","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1002\/jbmr.4527","article-title":"Melatonin prevents cartilage degradation in early-stage osteoarthritis through activation of miR-146a\/NRF2\/HO-1 Axis","volume":"37","author":"Zhou","year":"2022","journal-title":"J. Bone Min. Res."},{"key":"B115","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.ijcard.2014.07.095","article-title":"MicroRNA-29b promotes high-fat diet-stimulated endothelial permeability and apoptosis in apoE knock-out mice by down-regulating MT1 expression","volume":"176","author":"Zhu","year":"2014","journal-title":"Int. J. Cardiol."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.968919\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T04:58:09Z","timestamp":1664859489000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.968919\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,4]]},"references-count":115,"alternative-id":["10.3389\/fgene.2022.968919"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.968919","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,4]]},"article-number":"968919"}}