{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T19:50:58Z","timestamp":1778269858513,"version":"3.51.4"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T00:00:00Z","timestamp":1656028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003625","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["HI20C1496"],"award-info":[{"award-number":["HI20C1496"]}],"id":[{"id":"10.13039\/501100003625","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Osteoarthritis (OA) is the most common degenerative joint disease and is characterized by breakdown of joint cartilage. Coenzyme Q10 (CoQ10) exerts diverse biological effects on bone and cartilage; observational studies have suggested that CoQ10 may slow OA progression and inflammation. However, any effect of CoQ10 on OA remains unclear. Here, we investigated the therapeutic utility of CoQ10-micelles.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Seven-week-old male Wistar rats were injected with monosodium iodoacetate (MIA) to induce OA. CoQ10-micelles were administered orally to MIA-induced OA rats; celecoxib served as the positive control. Pain, tissue destruction, and inflammation were measured. The expression levels of catabolic and inflammatory cell death markers were assayed in CoQ10-micelle-treated chondrocytes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Oral supplementation with CoQ10-micelles attenuated OA symptoms remarkably, including pain, tissue destruction, and inflammation. The expression levels of the inflammatory cytokines IL-1\u03b2, IL-6, and MMP-13, and of the inflammatory cell death markers RIP1, RIP3, and pMLKL in synovial tissues were significantly reduced by CoQ10-micelle supplementation, suggesting that CoQ10-micelles might attenuate the synovitis of OA. CoQ10-micelle addition to cultured OA chondrocytes reduced the expression levels of catabolic and inflammatory cell death markers.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>CoQ10-micelles might usefully treat OA.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0270351","type":"journal-article","created":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T17:36:51Z","timestamp":1656092211000},"page":"e0270351","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Coenzyme Q10 encapsulated in micelles ameliorates osteoarthritis by inhibiting inflammatory cell death"],"prefix":"10.1371","volume":"17","author":[{"given":"Hyun Sik","family":"Na","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8921-2832","authenticated-orcid":true,"given":"Jin Seok","family":"Woo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju Hwan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong Su","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In Gyu","family":"Um","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keun-Hyung","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ga Hyeon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5715-3989","authenticated-orcid":true,"given":"Mi-La","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang J.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung-Hwan","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,6,24]]},"reference":[{"key":"pone.0270351.ref001","doi-asserted-by":"crossref","first-page":"16072","DOI":"10.1038\/nrdp.2016.72","article-title":"Osteoarthritis","volume":"2","author":"J Martel-Pelletier","year":"2016","journal-title":"Nat Rev Dis Primers"},{"issue":"8","key":"pone.0270351.ref002","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41584-020-0447-8","article-title":"Core and adjunctive interventions for osteoarthritis: efficacy and models for implementation","volume":"16","author":"JL Bowden","year":"2020","journal-title":"Nat Rev Rheumatol"},{"issue":"10182","key":"pone.0270351.ref003","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"DJ Hunter","year":"2019","journal-title":"Lancet"},{"issue":"3","key":"pone.0270351.ref004","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1002\/art.27305","article-title":"Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis","volume":"62","author":"B Carames","year":"2010","journal-title":"Arthritis Rheum"},{"issue":"11","key":"pone.0270351.ref005","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/nrrheum.2010.159","article-title":"The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis","volume":"6","author":"J Sellam","year":"2010","journal-title":"Nat Rev Rheumatol"},{"issue":"3","key":"pone.0270351.ref006","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.rehab.2016.01.006","article-title":"Risk factors and burden of osteoarthritis","volume":"59","author":"C Palazzo","year":"2016","journal-title":"Ann Phys Rehabil Med"},{"issue":"9","key":"pone.0270351.ref007","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1136\/annrheumdis-2013-203355","article-title":"Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: influences of age, gender and osteoarthritis affecting other joints","volume":"73","author":"D Prieto-Alhambra","year":"2014","journal-title":"Ann Rheum Dis"},{"issue":"12","key":"pone.0270351.ref008","doi-asserted-by":"crossref","first-page":"e007568","DOI":"10.1136\/bmjopen-2014-007568","article-title":"Body mass index and risk of knee osteoarthritis: systematic review and meta-analysis of prospective studies","volume":"5","author":"H Zheng","year":"2015","journal-title":"BMJ Open"},{"issue":"1","key":"pone.0270351.ref009","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nrrheum.2010.196","article-title":"Role of proinflammatory cytokines in the pathophysiology of osteoarthritis","volume":"7","author":"M Kapoor","year":"2011","journal-title":"Nat Rev Rheumatol"},{"issue":"9","key":"pone.0270351.ref010","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41573-021-00233-1","article-title":"Targeting oxidative stress in disease: promise and limitations of antioxidant therapy","volume":"20","author":"HJ Forman","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"pone.0270351.ref011","doi-asserted-by":"crossref","first-page":"8416763","DOI":"10.1155\/2017\/8416763","article-title":"Oxidative Stress: Harms and Benefits for Human Health","volume":"2017","author":"G Pizzino","year":"2017","journal-title":"Oxid Med Cell Longev"},{"key":"pone.0270351.ref012","doi-asserted-by":"crossref","first-page":"694","DOI":"10.3389\/fphys.2020.00694","article-title":"Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases","volume":"11","author":"M Sharifi-Rad","year":"2020","journal-title":"Front Physiol"},{"issue":"2","key":"pone.0270351.ref013","first-page":"71","article-title":"Coenzyme Q10: is there a clinical role and a case for measurement?","volume":"29","author":"SL Molyneux","year":"2008","journal-title":"Clin Biochem Rev"},{"issue":"6","key":"pone.0270351.ref014","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1080\/07315724.2001.10719063","article-title":"Biochemical functions of coenzyme Q10","volume":"20","author":"FL Crane","year":"2001","journal-title":"J Am Coll Nutr"},{"issue":"2","key":"pone.0270351.ref015","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3390\/healthcare3020296","article-title":"Supplementation of Coenzyme Q10 among Patients with Type 2 Diabetes Mellitus","volume":"3","author":"Q Shen","year":"2015","journal-title":"Healthcare (Basel)"},{"issue":"4","key":"pone.0270351.ref016","article-title":"Metabolic Targets of Coenzyme Q10 in Mitochondria","volume":"10","author":"A Hidalgo-Gutierrez","year":"2021","journal-title":"Antioxidants (Basel)"},{"issue":"12","key":"pone.0270351.ref017","article-title":"Associations between Coenzyme Q10 Status, Oxidative Stress, and Muscle Strength and Endurance in Patients with Osteoarthritis","volume":"9","author":"PS Chang","year":"2020","journal-title":"Antioxidants (Basel)"},{"issue":"12","key":"pone.0270351.ref018","article-title":"Role of Jumpstart Nutrition((R)), a Dietary Supplement, to Ameliorate Calcium-to-Phosphorus Ratio and Parathyroid Hormone of Patients with Osteoarthritis","volume":"7","author":"A. Ganguly","year":"2019","journal-title":"Med Sci (Basel)"},{"issue":"12","key":"pone.0270351.ref019","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.1007\/s10067-019-04723-x","article-title":"Effects of coenzyme Q10 supplementation on matrix metalloproteinases and DAS-28 in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled clinical trial","volume":"38","author":"SM Nachvak","year":"2019","journal-title":"Clin Rheumatol"},{"issue":"2","key":"pone.0270351.ref020","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3109\/08923973.2015.1122619","article-title":"Combination therapy with metformin and coenzyme Q10 in murine experimental autoimmune arthritis","volume":"38","author":"J Jhun","year":"2016","journal-title":"Immunopharmacol Immunotoxicol"},{"issue":"7","key":"pone.0270351.ref021","doi-asserted-by":"crossref","first-page":"e69362","DOI":"10.1371\/journal.pone.0069362","article-title":"Coenzyme Q10 ameliorates pain and cartilage degradation in a rat model of osteoarthritis by regulating nitric oxide and inflammatory cytokines","volume":"8","author":"J Lee","year":"2013","journal-title":"PLoS One"},{"issue":"8","key":"pone.0270351.ref022","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/ddr.21412","article-title":"Coenzyme Q10 Prevents the Interleukin-1 Beta Induced Inflammatory Response via Inhibition of MAPK Signaling Pathways in Rat Articular Chondrocytes","volume":"78","author":"X Li","year":"2017","journal-title":"Drug Dev Res"},{"issue":"2","key":"pone.0270351.ref023","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.imlet.2015.05.012","article-title":"Coenzyme Q10 suppresses Th17 cells and osteoclast differentiation and ameliorates experimental autoimmune arthritis mice","volume":"166","author":"J Jhun","year":"2015","journal-title":"Immunol Lett"},{"issue":"10","key":"pone.0270351.ref024","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.1007\/s12274-018-2152-3","article-title":"Strategies to improve micelle stability for drug delivery","volume":"11","author":"Y Lu","year":"2018","journal-title":"Nano Res"},{"key":"pone.0270351.ref025","first-page":"340315","article-title":"Polymeric micelles, a promising drug delivery system to enhance bioavailability of poorly water-soluble drugs","volume":"2013","author":"W Xu","year":"2013","journal-title":"J Drug Deliv"},{"key":"pone.0270351.ref026","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fphar.2014.00077","article-title":"Multifunctional polymeric micelles for delivery of drugs and siRNA","volume":"5","author":"AM Jhaveri","year":"2014","journal-title":"Front Pharmacol"},{"issue":"1","key":"pone.0270351.ref027","article-title":"Coenzyme Q10-Polyethylene Glycol Monostearate Nanoparticles: An Injectable Water-Soluble Formulation","volume":"9","author":"K Banshoya","year":"2020","journal-title":"Antioxidants (Basel)"},{"issue":"6","key":"pone.0270351.ref028","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.3904\/kjim.2019.269","article-title":"The therapeutic efficacy of water-soluble coenzyme Q10 in an experimental model of tacrolimus-induced diabetes mellitus","volume":"35","author":"Y Quan","year":"2020","journal-title":"Korean J Intern Med"},{"issue":"4","key":"pone.0270351.ref029","doi-asserted-by":"crossref","first-page":"949","DOI":"10.3904\/kjim.2020.211","article-title":"Water-soluble coenzyme Q10 provides better protection than lipid-soluble coenzyme Q10 in a rat model of chronic tacrolimus nephropathy","volume":"36","author":"S Cui","year":"2021","journal-title":"Korean J Intern Med"},{"issue":"1","key":"pone.0270351.ref030","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1007\/s12272-013-0010-0","article-title":"Augmented chondroprotective effect of coadministration of celecoxib and rebamipide in the monosodium iodoacetate rat model of osteoarthritis","volume":"36","author":"SJ Moon","year":"2013","journal-title":"Arch Pharm Res"},{"issue":"1","key":"pone.0270351.ref031","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrrheum.2013.159","article-title":"Progress in intra-articular therapy","volume":"10","author":"CH Evans","year":"2014","journal-title":"Nat Rev Rheumatol"},{"issue":"12","key":"pone.0270351.ref032","doi-asserted-by":"crossref","first-page":"3327","DOI":"10.1002\/art.38869","article-title":"Meta-analysis of assay sensitivity and study features in clinical trials of pharmacologic treatments for osteoarthritis pain","volume":"66","author":"RH Dworkin","year":"2014","journal-title":"Arthritis Rheumatol"},{"issue":"1","key":"pone.0270351.ref033","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.1038\/s41598-017-03110-3","article-title":"Knee Symptomatic Osteoarthritis, Walking Disability, NSAIDs Use and All-cause Mortality: Population-based Wuchuan Osteoarthritis Study","volume":"7","author":"Q Liu","year":"2017","journal-title":"Sci Rep"},{"issue":"2","key":"pone.0270351.ref034","doi-asserted-by":"crossref","DOI":"10.3390\/cells8020106","article-title":"ETF-QO Mutants Uncoupled Fatty Acid beta-Oxidation and Mitochondrial Bioenergetics Leading to Lipid Pathology","volume":"8","author":"S Chokchaiwong","year":"2019","journal-title":"Cells"},{"issue":"4","key":"pone.0270351.ref035","article-title":"Coenzyme Q10: Clinical Applications in Cardiovascular Diseases","volume":"9","author":"A Martelli","year":"2020","journal-title":"Antioxidants (Basel)"},{"issue":"4","key":"pone.0270351.ref036","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1002\/fsn3.1492","article-title":"The effect of coenzyme Q10 supplementation on oxidative stress: A systematic review and meta-analysis of randomized controlled clinical trials","volume":"8","author":"ZS Sangsefidi","year":"2020","journal-title":"Food Sci Nutr"},{"issue":"8","key":"pone.0270351.ref037","article-title":"Role of Coenzyme Q10 in Health and Disease: An Update on the Last 10 Years (2010\u20132020)","volume":"10","author":"I Cirilli","year":"2021","journal-title":"Antioxidants (Basel)"},{"issue":"5","key":"pone.0270351.ref038","article-title":"Coenzyme Q10 and Immune Function: An Overview","volume":"10","author":"D Mantle","year":"2021","journal-title":"Antioxidants (Basel)"},{"issue":"5","key":"pone.0270351.ref039","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1172\/JCI80276","article-title":"Multiple myeloma-derived MMP-13 mediates osteoclast fusogenesis and osteolytic disease","volume":"126","author":"J Fu","year":"2016","journal-title":"J Clin Invest"},{"key":"pone.0270351.ref040","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.cellsig.2018.10.005","article-title":"Interleukin-1beta signaling in osteoarthritis\u2014chondrocytes in focus","volume":"53","author":"Z Jenei-Lanzl","year":"2019","journal-title":"Cell Signal"},{"key":"pone.0270351.ref041","doi-asserted-by":"crossref","first-page":"730","DOI":"10.3389\/fimmu.2020.00730","article-title":"Interleukin-1-Interleukin-17 Signaling Axis Induces Cartilage Destruction and Promotes Experimental Osteoarthritis","volume":"11","author":"HS Na","year":"2020","journal-title":"Front Immunol"},{"issue":"3","key":"pone.0270351.ref042","article-title":"Metformin Attenuates Monosodium-Iodoacetate-Induced Osteoarthritis via Regulation of Pain Mediators and the Autophagy-Lysosomal Pathway","volume":"10","author":"HS Na","year":"2021","journal-title":"Cells"},{"issue":"5","key":"pone.0270351.ref043","doi-asserted-by":"crossref","DOI":"10.3390\/cells10051057","article-title":"Oral Administration of Lactobacillus rhamnosus Ameliorates the Progression of Osteoarthritis by Inhibiting Joint Pain and Inflammation","volume":"10","author":"J Jhun","year":"2021","journal-title":"Cells"},{"key":"pone.0270351.ref044","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.imlet.2020.10.008","article-title":"Combinatmarion treatment with Lactobacillus acidophilus LA-1, vitamin B, and curcumin ameliorates the progression of osteoarthritis by inhibiting the pro-inflammatory mediators","volume":"228","author":"J Jhun","year":"2020","journal-title":"Immunol Lett"},{"issue":"5","key":"pone.0270351.ref045","doi-asserted-by":"crossref","DOI":"10.3390\/nu13051697","article-title":"Coenzyme Q10: Clinical Applications beyond Cardiovascular Diseases","volume":"13","author":"L Testai","year":"2021","journal-title":"Nutrients"},{"issue":"8","key":"pone.0270351.ref046","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1001\/archneurol.2012.206","article-title":"Heterogeneity of coenzyme Q10 deficiency: patient study and literature review","volume":"69","author":"V Emmanuele","year":"2012","journal-title":"Arch Neurol"},{"issue":"1","key":"pone.0270351.ref047","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1089\/jmf.2017.3952","article-title":"A Combination with Probiotic Complex, Zinc, and Coenzyme Q10 Attenuates Autoimmune Arthritis by Regulation of Th17\/Treg Balance","volume":"21","author":"SY Lee","year":"2018","journal-title":"J Med Food"},{"issue":"5","key":"pone.0270351.ref048","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.14336\/AD.2019.1127","article-title":"Pyroptosis Plays a Role in Osteoarthritis","volume":"11","author":"S An","year":"2020","journal-title":"Aging Dis"},{"key":"pone.0270351.ref049","doi-asserted-by":"crossref","first-page":"638382","DOI":"10.3389\/fcell.2021.638382","article-title":"RIP1 Perturbation Induces Chondrocyte Necroptosis and Promotes Osteoarthritis Pathogenesis via Targeting BMP7","volume":"9","author":"J Cheng","year":"2021","journal-title":"Front Cell Dev Biol"},{"issue":"1","key":"pone.0270351.ref050","doi-asserted-by":"crossref","first-page":"3151","DOI":"10.1038\/s41467-020-16887-1","article-title":"MLKL trafficking and accumulation at the plasma membrane control the kinetics and threshold for necroptosis","volume":"11","author":"AL Samson","year":"2020","journal-title":"Nat Commun"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0270351","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T17:37:40Z","timestamp":1656092260000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0270351"}},"subtitle":[],"editor":[{"given":"Rosanna","family":"Di Paola","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,6,24]]},"references-count":50,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0270351","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,24]]}}}