{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T22:58:11Z","timestamp":1769554691440,"version":"3.49.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Temporomandibular joint osteoarthritis (TMJOA) condylar cartilage degeneration and abnormal subchondral bone pathological remodeling induce pain and joint dysfunction, and cartilage degeneration is considered irreversible. Very few therapeutic approaches are administrated in practice. Nucleotides have demonstrated considerable potential as a next-generation medication, and they have been applied in several models of osteoarthritis. There is a need to establish an effective protocol for TMJOA gene therapy. In the current study unilateral anterior crossbite (UAC) surgery was used to simulate mechanical stress-induced TMJOA in mice. Degeneration of condylar cartilage and destruction of subchondral bone were observed in damaged joints, and miR-181a-5p was elevated in chondrocytes. Intra-articular injection of miR-181a-5p antisense oligonucleotide (ASO) could reduce the cartilage damage and alleviate UAC-induced TMJOA progression, but it did not restore injured subchondral bone. Mechanically, miR-181a-5p evidently targeted the 3\u2019 untranslated region of <jats:italic>Sirt1<\/jats:italic> directly, resulting in inhibition of silent information regulator 1 expression and promoting apoptosis by elevating p53-dependent signaling, indicating that miR181a-5p ASO promoted chondrocyte survival. The present study suggests that ASO-based gene therapy may be an effective TMJOA treatment.<\/jats:p>","DOI":"10.3389\/fphar.2022.898334","type":"journal-article","created":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T05:58:11Z","timestamp":1655272691000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Antisense Oligonucleotide-Based Therapy on miR-181a-5p Alleviates Cartilage Degradation of Temporomandibular Joint Osteoarthritis via Promoting SIRT1"],"prefix":"10.3389","volume":"13","author":[{"given":"Hexu","family":"Qi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenxing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihe","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010137","article-title":"RNA-based Therapeutics: From Antisense Oligonucleotides to miRNAs","volume":"9","author":"Bajan","year":"2020","journal-title":"Cells"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1136\/annrheumdis-2020-217072","article-title":"Serum NT\/CT SIRT1 Ratio Reflects Early Osteoarthritis and Chondrosenescence","volume":"79","author":"Batshon","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21103601","article-title":"MicroRNAs in Intervertebral Disc Degeneration, Apoptosis, Inflammation, and Mechanobiology","volume":"21","author":"Cazzanelli","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"79S","DOI":"10.1177\/0022034514565793","article-title":"Temporomandibular Joint Disorders' Impact on Pain, Function, and Disability","volume":"94","author":"Chantaracherd","year":"2015","journal-title":"J. Dent. Res."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20190189","article-title":"The Role of Sirtuin 1 and its Activator, Resveratrol in Osteoarthritis","volume":"39","author":"Deng","year":"2019","journal-title":"Biosci. Rep."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9062004","article-title":"Antisense Oligonucleotides: An Emerging Area in Drug Discovery and Development","volume":"9","author":"Dhuri","year":"2020","journal-title":"J. Clin. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1111\/nyas.14606","article-title":"Overloading Stress-Induced Progressive Degeneration and Self-Repair in Condylar Cartilage","volume":"1503","author":"Fang","year":"2021","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2016.36","article-title":"Pharmacokinetics and Pharmacodynamics of a 13-mer LNA-Inhibitor-miR-221 in Mice and Non-human Primates","volume":"5","author":"Gallo Cantafio","year":"2016","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"B9","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1038\/nrrheum.2016.148","article-title":"Changes in the Osteochondral Unit during Osteoarthritis: Structure, Function and Cartilage-Bone Crosstalk","volume":"12","author":"Goldring","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"393","DOI":"10.14348\/molcells.2017.0018","article-title":"Peroxisome Proliferator-Activated Receptor \u03b1 Facilitates Osteogenic Differentiation in MC3T3-E1 Cells via the Sirtuin 1-Dependent Signaling Pathway","volume":"40","author":"Gong","year":"2017","journal-title":"Mol. Cells"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218089","article-title":"Microenvironment in Subchondral Bone: Predominant Regulator for the Treatment of Osteoarthritis","volume":"6","author":"Hu","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41413-021-00147-z","article-title":"Subchondral Bone Microenvironment in Osteoarthritis and Pain","volume":"9","author":"Hu","year":"2021","journal-title":"Bone Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1056\/NEJMoa1209026","article-title":"Treatment of HCV Infection by Targeting microRNA","volume":"368","author":"Janssen","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/nrd3625","article-title":"RNA Therapeutics: beyond RNA Interference and Antisense Oligonucleotides","volume":"11","author":"Kole","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"B15","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s13018-017-0542-y","article-title":"MiRNA Expression in the Cartilage of Patients with Osteoarthritis","volume":"12","author":"Kopa\u0144ska","year":"2017","journal-title":"J. Orthop. Surg. Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.ajodo.2012.08.024","article-title":"Combined Degenerative and Regenerative Remodeling Responses of the Mandibular Condyle to Experimentally Induced Disordered Occlusion","volume":"143","author":"Kuang","year":"2013","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"B17","first-page":"245","article-title":"SIRT1 Phosphorylation by AMP-Activated Protein Kinase Regulates P53 Acetylation","volume":"4","author":"Lau","year":"2014","journal-title":"Am. J. Cancer Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"4902","DOI":"10.1111\/jcmm.16514","article-title":"Pathological Mechanism of Chondrocytes and the Surrounding Environment during Osteoarthritis of Temporomandibular Joint","volume":"25","author":"Li","year":"2021","journal-title":"J. Cell Mol. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41368-020-00095-0","article-title":"Nociceptive Behavioural Assessments in Mouse Models of Temporomandibular Joint Disorders","volume":"12","author":"Li","year":"2020","journal-title":"Int. J. Oral Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/s13018-016-0477-8","article-title":"The Expression of SIRT1 in Articular Cartilage of Patients with Knee Osteoarthritis and its Correlation with Disease Severity","volume":"11","author":"Li","year":"2016","journal-title":"J. Orthop. Surg. Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1038\/s41419-018-0994-y","article-title":"MicroRNA-128a Represses Chondrocyte Autophagy and Exacerbates Knee Osteoarthritis by Disrupting Atg12","volume":"9","author":"Lian","year":"2018","journal-title":"Cell Death Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/j.joca.2020.12.016","article-title":"Initiation and Progression of Dental-Stimulated Temporomandibular Joints Osteoarthritis","volume":"29","author":"Liu","year":"2021","journal-title":"Osteoarthr. Cartil."},{"key":"B23","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s00167-010-1054-z","article-title":"The Basic Science of the Subchondral Bone","volume":"18","author":"Madry","year":"2010","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e136","DOI":"10.1093\/nar\/gkr646","article-title":"The microRNA Body Map: Dissecting microRNA Function through Integrative Genomics","volume":"39","author":"Mestdagh","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"115461","DOI":"10.1016\/j.bone.2020.115461","article-title":"Antisense Oligonucleotide-Based Therapies for the Treatment of Osteoarthritis: Opportunities and Roadblocks","volume":"138","author":"Nakamura","year":"2020","journal-title":"Bone"},{"key":"B26","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1136\/annrheumdis-2018-213629","article-title":"microRNA-181a-5p Antisense Oligonucleotides Attenuate Osteoarthritis in Facet and Knee Joints","volume":"78","author":"Nakamura","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e86820","DOI":"10.1172\/jci.insight.86820","article-title":"Identification of microRNA-181a-5p and microRNA-4454 as Mediators of Facet Cartilage Degeneration","volume":"1","author":"Nakamura","year":"2016","journal-title":"JCI Insight"},{"key":"B28","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.jot.2021.11.007","article-title":"Hemodynamic Stress Shapes Subchondral Bone in Osteoarthritis: An Emerging Hypothesis","volume":"32","author":"Ni","year":"2022","journal-title":"J. Orthop. Transl."},{"key":"B29","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.arr.2018.02.004","article-title":"Role of Sirtuin1-P53 Regulatory axis in Aging, Cancer and Cellular Reprogramming","volume":"43","author":"Ong","year":"2018","journal-title":"Ageing Res. Rev."},{"key":"B30","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1177\/0022034517707515","article-title":"Association of Condylar Bone Quality with TMJ Osteoarthritis","volume":"96","author":"Shi","year":"2017","journal-title":"J. Dent. Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1093\/abbs\/gmab043","article-title":"Exosomal lncRNA-P21 Derived from Mesenchymal Stem Cells Protects Epithelial Cells during LPS-Induced Acute Lung Injury by Sponging miR-181","volume":"53","author":"Sui","year":"2021","journal-title":"Acta Biochim. Biophys. Sin. (Shanghai)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.bone.2011.10.010","article-title":"Osteochondral Alterations in Osteoarthritis","volume":"51","author":"Suri","year":"2012","journal-title":"Bone"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1016\/s1470-2045(17)30621-6","article-title":"Safety and Activity of microRNA-Loaded Minicells in Patients with Recurrent Malignant Pleural Mesothelioma: a First-In-Man, Phase 1, Open-Label, Dose-Escalation Study","volume":"18","author":"van Zandwijk","year":"2017","journal-title":"Lancet Oncol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1177\/0022034515574770","article-title":"Current Understanding of Pathogenesis and Treatment of TMJ Osteoarthritis","volume":"94","author":"Wang","year":"2015","journal-title":"J. Dent. Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1111\/odi.12112","article-title":"Cartilage Degradation in Temporomandibular Joint Induced by Unilateral Anterior Crossbite Prosthesis","volume":"20","author":"Wang","year":"2014","journal-title":"Oral Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"4830","DOI":"10.1016\/j.bioactmat.2021.05.011","article-title":"Articular Cartilage and Osteochondral Tissue Engineering Techniques: Recent Advances and Challenges","volume":"6","author":"Wei","year":"2021","journal-title":"Bioact. Mater"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.2147\/JPR.S303536","article-title":"Animal Models of Temporomandibular Disorder","volume":"14","author":"Xiang","year":"2021","journal-title":"J. Pain Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.bbrc.2020.04.097","article-title":"Epigenetic Regulation of Chondrocyte Hypertrophy and Apoptosis through Sirt1\/P53\/P21 Pathway in Surgery-Induced Osteoarthritis","volume":"528","author":"Xu","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B39","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1186\/s12891-018-2273-6","article-title":"The Hsa-miR-181a-5p Reduces Oxidation Resistance by Controlling SECISBP2 in Osteoarthritis","volume":"19","author":"Xue","year":"2018","journal-title":"BMC Musculoskelet. Disord."},{"key":"B40","doi-asserted-by":"publisher","first-page":"201","DOI":"10.3892\/ijmm.2016.2618","article-title":"MicroRNA-34a Affects Chondrocyte Apoptosis and Proliferation by Targeting the SIRT1\/p53 Signaling Pathway during the Pathogenesis of Osteoarthritis","volume":"38","author":"Yan","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1080\/15548627.2019.1606647","article-title":"MTORC1 Coordinates the Autophagy and Apoptosis Signaling in Articular Chondrocytes in Osteoarthritic Temporomandibular Joint","volume":"16","author":"Yang","year":"2020","journal-title":"Autophagy"},{"key":"B42","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.jot.2020.09.006","article-title":"Chondrocyte Ferroptosis Contribute to the Progression of Osteoarthritis","volume":"27","author":"Yao","year":"2021","journal-title":"J. Orthop. Transl."},{"key":"B43","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1111\/joor.12757","article-title":"Catabolic Changes of Rat Temporomandibular Joint Discs Induced by Unilateral Anterior Crossbite","volume":"46","author":"Zhang","year":"2019","journal-title":"J. Oral Rehabil."},{"key":"B44","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1177\/0022034512473482","article-title":"Occlusal Effects on Longitudinal Bone Alterations of the Temporomandibular Joint","volume":"92","author":"Zhang","year":"2013","journal-title":"J. Dent. Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.tips.2014.03.005","article-title":"Targeting TGF\u03b2 Signaling in Subchondral Bone and Articular Cartilage Homeostasis","volume":"35","author":"Zhen","year":"2014","journal-title":"Trends Pharmacol. Sci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"661852","DOI":"10.3389\/fphys.2021.661852","article-title":"Protective Effect of SIRT1 Activator on the Knee with Osteoarthritis","volume":"12","author":"Zhou","year":"2021","journal-title":"Front. Physiol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.898334\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T05:58:17Z","timestamp":1655272697000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.898334\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,15]]},"references-count":46,"alternative-id":["10.3389\/fphar.2022.898334"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.898334","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,15]]},"article-number":"898334"}}