{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:48:46Z","timestamp":1787237326932,"version":"build-2736575974"},"reference-count":50,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:00:00Z","timestamp":1630540800000},"content-version":"vor","delay-in-days":366,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","clinicalkey.es","oarsijournal.com","clinicalkey.com.au","clinicalkey.fr","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Osteoarthritis and Cartilage"],"published-print":{"date-parts":[[2020,9]]},"DOI":"10.1016\/j.joca.2020.06.005","type":"journal-article","created":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T20:38:50Z","timestamp":1593808730000},"page":"1265-1275","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":58,"title":["Systemic iron overload exacerbates osteoarthritis in the strain 13 guinea pig"],"prefix":"10.1016","volume":"28","author":[{"given":"L.H.","family":"Burton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.B.","family":"Radakovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.J.","family":"Marolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.S.","family":"Santangelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"5","key":"10.1016\/j.joca.2020.06.005_bib1","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1007\/BF02159268","article-title":"The rate constant of the bimolecular reaction between hydrogen peroxide and ferrous ion","volume":"10","author":"Rigg","year":"1954","journal-title":"Experientia"},{"issue":"4","key":"10.1016\/j.joca.2020.06.005_bib2","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1021\/ar50088a003","article-title":"Fenton's reagent revisited","volume":"8","author":"Walling","year":"1975","journal-title":"Acc Chem Res"},{"issue":"1","key":"10.1016\/j.joca.2020.06.005_bib3","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1196\/annals.1297.063","article-title":"Iron accumulation during cellular senescence","volume":"1019","author":"Killilea","year":"2004","journal-title":"Ann N Y Acad Sci"},{"key":"10.1016\/j.joca.2020.06.005_bib4","doi-asserted-by":"crossref","unstructured":"Zacharski LR, Ornstein DL, Woloshin S, Schwartz LM. Association of age, sex, and race with body iron stores in adults: analysis of NHANES III data. Am Heart J;140 (1):98\u2013104. doi:10.1067\/mhj.2000.106646.","DOI":"10.1067\/mhj.2000.106646"},{"issue":"7\u20138","key":"10.1016\/j.joca.2020.06.005_bib5","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.mad.2010.04.007","article-title":"The emerging role of iron dyshomeostasis in the mitochondrial decay of aging","volume":"131","author":"Xu","year":"2010","journal-title":"Mech Ageing Dev"},{"issue":"14","key":"10.1016\/j.joca.2020.06.005_bib6","article-title":"Hepcidin: a promising therapeutic target for iron disorders","volume":"95","author":"Liu","year":"2016","journal-title":"Med (United States)."},{"issue":"3","key":"10.1016\/j.joca.2020.06.005_bib7","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.joca.2015.09.007","article-title":"Iron overload in a murine model of hereditary hemochromatosis is associated with accelerated progression of osteoarthritis under mechanical stress","volume":"24","author":"Camacho","year":"2016","journal-title":"Osteoarthritis Cartilage"},{"issue":"10","key":"10.1016\/j.joca.2020.06.005_bib8","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1002\/art.1780291002","article-title":"Intraarticular ferritin-bound iron in rheumatoid arthritis. A factor that increases oxygen free radical-induced tissue destruction","volume":"29","author":"Biemond","year":"1986","journal-title":"Arthritis Rheum"},{"issue":"11","key":"10.1016\/j.joca.2020.06.005_bib9","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1039\/c0mt00023j","article-title":"The hazards of iron loading","volume":"2","author":"Weinberg","year":"2010","journal-title":"Metall"},{"issue":"4","key":"10.1016\/j.joca.2020.06.005_bib10","doi-asserted-by":"crossref","first-page":"e218","DOI":"10.1111\/hae.12208","article-title":"Identification and expression of iron regulators in human synovium: evidence for upregulation in haemophilic arthropathy compared to rheumatoid arthritis, osteoarthritis, and healthy controls","volume":"19","author":"Nieuwenhuizen","year":"2013","journal-title":"Haemophilia"},{"issue":"5797","key":"10.1016\/j.joca.2020.06.005_bib11","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1136\/bmj.1.5797.418","article-title":"Arthropathy in transfusional siderosis","volume":"1","author":"Abbott","year":"1972","journal-title":"Br Med J"},{"issue":"6","key":"10.1016\/j.joca.2020.06.005_bib12","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1093\/rheumatology\/keg220","article-title":"Haemoglobin-derived iron-dependent hydroxyl radical formation in blood-induced joint damage: an in vitro study","volume":"42","author":"Hooiveld","year":"2003","journal-title":"Rheumatology (Oxford)"},{"issue":"5","key":"10.1016\/j.joca.2020.06.005_bib13","doi-asserted-by":"crossref","first-page":"413","DOI":"10.3109\/03009741003677449","article-title":"Ferritin concentrations in synovial fluid are higher in osteoarthritis patients with HFE gene mutations (C282Y or H63D)","volume":"39","author":"Carroll","year":"2010","journal-title":"Scand J Rheumatol"},{"issue":"6","key":"10.1016\/j.joca.2020.06.005_bib14","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/0002-9343(83)90875-6","article-title":"Arthritis of hemochromatosis. Clinical spectrum, relation to histocompatibility antigens, and effectiveness of early phlebotomy","volume":"75","author":"Askari","year":"1983","journal-title":"Am J Med"},{"issue":"1","key":"10.1016\/j.joca.2020.06.005_bib15","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.berh.2009.08.006","article-title":"Why is osteoarthritis an age-related disease?","volume":"24","author":"Anderson","year":"2010","journal-title":"Best Pract Res Clin Rheumatol"},{"issue":"5","key":"10.1016\/j.joca.2020.06.005_bib16","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.berh.2019.04.004","article-title":"The role of ferritin and adiponectin as predictors of cartilage damage assessed by arthroscopy in patients with symptomatic knee osteoarthritis","volume":"32","author":"Nugzar","year":"2018","journal-title":"Best Pract Res Clin Rheumatol"},{"issue":"2","key":"10.1016\/j.joca.2020.06.005_bib17","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1385\/BTER:106:2:123","article-title":"Synovial fluid and plasma selenium, copper, zinc, and iron concentrations in patients with rheumatoid arthritis and osteoarthritis","volume":"106","author":"Yazer","year":"2005","journal-title":"Biol Trace Elem Res"},{"issue":"1","key":"10.1016\/j.joca.2020.06.005_bib18","first-page":"30","article-title":"Synovial iron deposition in osteoarthritis and rheumatoid arthritis","volume":"7","author":"Ogilvie-Harris","year":"1980","journal-title":"J\u00a0Rheumatol"},{"issue":"Suppl 3","key":"10.1016\/j.joca.2020.06.005_bib19","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.1016\/j.joca.2010.04.015","article-title":"The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the Guinea pig","volume":"18","author":"Kraus","year":"2010","journal-title":"Osteoarthritis Cartilage"},{"issue":"3","key":"10.1016\/j.joca.2020.06.005_bib20","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1177\/019262339302100307","article-title":"Morphologic investigations of the Guinea pig model of iron overload","volume":"21","author":"Schwartz","year":"1993","journal-title":"Toxicol Pathol"},{"key":"10.1016\/j.joca.2020.06.005_bib21","series-title":"Association of Official Analytical Chemists. Official Methods of Analysis of AOAC International","year":"1990"},{"key":"10.1016\/j.joca.2020.06.005_bib22","series-title":"Association of Official Analytical Chemists. Official Methods of Analysis of AOAC International","year":"1990"},{"key":"10.1016\/j.joca.2020.06.005_bib23","series-title":"Association of Official Analytical Chemists. Official Methods of Analysis of AOAC International","year":"1990"},{"issue":"5","key":"10.1016\/j.joca.2020.06.005_bib24","doi-asserted-by":"crossref","DOI":"10.1177\/1759091416670978","article-title":"Enhanced histochemical detection of iron in paraffin sections of mouse central nervous system tissue: application in the APP\/PS1 mouse model of alzheimers disease","volume":"8","author":"Sands","year":"2016","journal-title":"ASN Neuro"},{"key":"10.1016\/j.joca.2020.06.005_bib25","first-page":"1","article-title":"Development of a microcomputed tomography scoring system to characterize disease progression in the Hartley Guinea pig model of spontaneous osteoarthritis","author":"Radakovich","year":"2017","journal-title":"Connect Tissue Res"},{"issue":"6","key":"10.1016\/j.joca.2020.06.005_bib26","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1177\/1941738109350438","article-title":"The basic science of articular cartilage: structure, composition, and function","volume":"1","author":"Sophia Fox","year":"2009","journal-title":"Sport Health"},{"key":"10.1016\/j.joca.2020.06.005_bib27","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1532-429X-11-20","article-title":"The efficacy of iron chelator regimes in reducing cardiac and hepatic iron in patients with thalassaemia major: a clinical observational study","volume":"11","author":"Berdoukas","year":"2009","journal-title":"J\u00a0Cardiovasc Magn Reson"},{"issue":"3","key":"10.1016\/j.joca.2020.06.005_bib28","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/j.1572-0241.1998.00346.x","article-title":"Hepatic iron concentration in hereditary hemochromatosis does not saturate or accurately predict phlebotomy requirements","volume":"93","author":"Olynyk","year":"1998","journal-title":"Am J Gastroenterol"},{"issue":"2","key":"10.1016\/j.joca.2020.06.005_bib29","first-page":"97","article-title":"Pathophysiology of obesity on knee joint homeostasis: contributions of the infrapatellar fat pad","volume":"26","author":"Santangelo","year":"2016","journal-title":"Horm Mol Biol Clin Invest"},{"issue":"7","key":"10.1016\/j.joca.2020.06.005_bib30","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.joca.2010.03.014","article-title":"The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: a narrative review","volume":"18","author":"Clockaerts","year":"2010","journal-title":"Osteoarthritis Cartilage"},{"issue":"1","key":"10.1016\/j.joca.2020.06.005_bib31","first-page":"94","article-title":"Infrapatellar fat pad syndrome: a review of anatomy, function, treatment and dynamics","volume":"82","author":"Mace","year":"2016","journal-title":"Acta Orthop Belg"},{"issue":"6","key":"10.1016\/j.joca.2020.06.005_bib32","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/ar4422","article-title":"An emerging player in knee osteoarthritis: the infrapatellar fat pad","volume":"15","author":"Ioan-Facsinay","year":"2013","journal-title":"Arthritis Res Ther"},{"issue":"9","key":"10.1016\/j.joca.2020.06.005_bib33","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1093\/gerona\/glv151","article-title":"Effect of aging on adipose tissue inflammation in the knee joints of F344BN rats","volume":"71","author":"Fu","year":"2016","journal-title":"J\u00a0Gerontol A Biol Sci Med Sci"},{"issue":"4","key":"10.1016\/j.joca.2020.06.005_bib34","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0060706","article-title":"Initial responses of articular tissues in a murine high-fat diet-induced osteoarthritis model: pivotal role of the IPFP as a cytokine fountain","volume":"8","author":"Iwata","year":"2013","journal-title":"PloS One"},{"issue":"10","key":"10.1016\/j.joca.2020.06.005_bib35","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1053\/joca.2002.0821","article-title":"A\u00a0comparative analysis of bone and cartilage metabolism in two strains of Guinea-pig with varying degrees of naturally occurring osteoarthritis","volume":"10","author":"Huebner","year":"2002","journal-title":"Osteoarthritis Cartilage"},{"issue":"Suppl A","key":"10.1016\/j.joca.2020.06.005_bib36","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1016\/j.joca.2003.09.003","article-title":"Are osteophytes good or bad?","volume":"12","author":"Menkes","year":"2004","journal-title":"Osteoarthritis Cartilage"},{"issue":"3","key":"10.1016\/j.joca.2020.06.005_bib37","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.joca.2006.11.006","article-title":"Osteophytes: relevance and biology","volume":"15","author":"van der Kraan","year":"2007","journal-title":"Osteoarthritis Cartilage"},{"issue":"1","key":"10.1016\/j.joca.2020.06.005_bib38","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1093\/rheumatology\/keh411","article-title":"Osteophytes and progression of knee osteoarthritis","volume":"44","author":"Felson","year":"2005","journal-title":"Rheumatology"},{"issue":"1","key":"10.1016\/j.joca.2020.06.005_bib39","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1002\/art.30094","article-title":"Hereditary hemochromatosis is characterized by a clinically definable arthropathy that correlates with iron load","volume":"63","author":"Carroll","year":"2011","journal-title":"Arthritis Rheum"},{"issue":"25","key":"10.1016\/j.joca.2020.06.005_bib40","doi-asserted-by":"crossref","first-page":"13160","DOI":"10.1074\/jbc.M115.691543","article-title":"Transforming growth factor \u03b21 (TGF-\u03b21) activates hepcidin mRNA expression in hepatocytes","volume":"291","author":"Chen","year":"2016","journal-title":"J\u00a0Biol Chem"},{"issue":"6","key":"10.1016\/j.joca.2020.06.005_bib41","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.cmet.2005.10.010","article-title":"A\u00a0role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression","volume":"2","author":"Wang","year":"2005","journal-title":"Cell Metabol"},{"issue":"4","key":"10.1016\/j.joca.2020.06.005_bib42","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/biof.1520","article-title":"Intracellular iron uptake is favored in Hfe-KO mouse primary chondrocytes mimicking an osteoarthritis-related phenotype","volume":"45","author":"Simao","year":"2019","journal-title":"Biofactors"},{"issue":"3","key":"10.1016\/j.joca.2020.06.005_bib43","first-page":"297","article-title":"Alterations in chondrocytes morphology, proliferation and binding","volume":"38","author":"Kirkpatrick","year":"1982","journal-title":"Virchows Arch B Cell Pathol Incl Mol Pathol"},{"issue":"1","key":"10.1016\/j.joca.2020.06.005_bib44","doi-asserted-by":"crossref","first-page":"95","DOI":"10.5312\/wjo.v6.i1.95","article-title":"Cytokines as biochemical markers for knee osteoarthritis","volume":"6","author":"Mabey","year":"2015","journal-title":"World J Orthoped"},{"issue":"1","key":"10.1016\/j.joca.2020.06.005_bib45","doi-asserted-by":"crossref","first-page":"3451","DOI":"10.1038\/s41598-017-03759-w","article-title":"IL-6 secretion in osteoarthritis patients is mediated by chondrocyte-synovial fibroblast cross-talk and is enhanced by obesity","volume":"7","author":"Pearson","year":"2017","journal-title":"Sci Rep"},{"issue":"9","key":"10.1016\/j.joca.2020.06.005_bib46","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1016\/j.bbamcr.2012.05.010","article-title":"Mammalian iron metabolism and its control by iron regulatory proteins","volume":"1823","author":"Anderson","year":"2012","journal-title":"Biochim Biophys Acta"},{"issue":"3","key":"10.1016\/j.joca.2020.06.005_bib47","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0092-8674(04)00343-5","article-title":"Balancing acts: molecular control of mammalian iron metabolism","volume":"117","author":"Hentze","year":"2004","journal-title":"Cell"},{"key":"10.1016\/j.joca.2020.06.005_bib48","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.exer.2016.12.008","article-title":"Iron importers zip8 and zip14 are expressed in retina and regulated by retinal iron levels","volume":"155","author":"Sterling","year":"2017","journal-title":"Exp Eye Res"},{"issue":"25","key":"10.1016\/j.joca.2020.06.005_bib49","doi-asserted-by":"crossref","first-page":"9175","DOI":"10.1073\/pnas.1405355111","article-title":"An iron-regulated and glycosylation-dependent proteasomal degradation pathway for the plasma membrane metal transporter zip14","volume":"111","author":"Zhao","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"10.1016\/j.joca.2020.06.005_bib50","first-page":"141","article-title":"Thalassemia major in adults: short stature, hyperpigmentation, inadequate chelation, and transfusion-transmitted infections are key features","volume":"4","author":"Prakash","year":"2012","journal-title":"N\u00a0Am J Med Sci"}],"container-title":["Osteoarthritis and Cartilage"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1063458420310566?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1063458420310566?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T07:44:01Z","timestamp":1696319041000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1063458420310566"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":50,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["S1063458420310566"],"URL":"https:\/\/doi.org\/10.1016\/j.joca.2020.06.005","relation":{},"ISSN":["1063-4584"],"issn-type":[{"value":"1063-4584","type":"print"}],"subject":[],"published":{"date-parts":[[2020,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Systemic iron overload exacerbates osteoarthritis in the strain 13 guinea pig","name":"articletitle","label":"Article Title"},{"value":"Osteoarthritis and Cartilage","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.joca.2020.06.005","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}