{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:01:36Z","timestamp":1790503296955,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773372"],"award-info":[{"award-number":["81773372"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81573104"],"award-info":[{"award-number":["81573104"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Kashin\u2013Beck disease (KBD) is a complex endemic osteoarthropathy, which mainly occurs in the northeast to southwest China. Iodothyronine deiodinases 3 (DIO3) is one of the selenoproteins, which is closely related to bone metabolism and unclear to KBD. This study aims to investigate the role and associated mechanisms of methylation and expression of <jats:italic>DIO3<\/jats:italic> with disease severity in patients with KBD. We performed a bioinformatics analysis first to identify the biological mechanisms involved in selenoproteins. The methylation status of the\u00a0<jats:italic>DIO3<\/jats:italic> gene and <jats:italic>DIO3<\/jats:italic> gene expression, as well as <jats:italic>DIO3<\/jats:italic>\u2010related regulatory genes in patients with KBD, were analyzed. We found that 15 CpG sites of six selenoproteins were hypomethylated with 5\u2010azacytidine treatment. <jats:italic>DIO3<\/jats:italic> hypermethylation was associated with an increased risk of KBD and may lead to downregulation of <jats:italic>DIO3<\/jats:italic> gene expression as well as be an indicator of the severity of KBD, which may provide a new insight for gene\u2013environment correlations and interactions in etiology and pathogenesis of KBD.<\/jats:p>","DOI":"10.1002\/jcp.29809","type":"journal-article","created":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T07:39:38Z","timestamp":1590565178000},"page":"9946-9957","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effects of methylation of deiodinase 3 gene on gene expression and severity of Kashin\u2013Beck disease"],"prefix":"10.1002","volume":"235","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1331-0089","authenticated-orcid":false,"given":"Zhaofang","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Endemic Diseases and Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, School of Public Health, Xi\u2032an Jiaotong University Health Science Center  Xi\u2032an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases and Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, School of Public Health, Xi\u2032an Jiaotong University Health Science Center  Xi\u2032an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases and Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, School of Public Health, Xi\u2032an Jiaotong University Health Science Center  Xi\u2032an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases and Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, School of Public Health, Xi\u2032an Jiaotong University Health Science Center  Xi\u2032an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongqiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases and Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, School of Public Health, Xi\u2032an Jiaotong University Health Science Center  Xi\u2032an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8659-7359","authenticated-orcid":false,"given":"Dandan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases and Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, School of Public Health, Xi\u2032an Jiaotong University Health Science Center  Xi\u2032an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuena","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases and Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, School of Public Health, Xi\u2032an Jiaotong University Health Science Center  Xi\u2032an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases and Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, School of Public Health, Xi\u2032an Jiaotong University Health Science Center  Xi\u2032an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiwang","family":"Tan","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases and Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, School of Public Health, Xi\u2032an Jiaotong University Health Science Center  Xi\u2032an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8263-2970","authenticated-orcid":false,"given":"Yongmin","family":"Xiong","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases and Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, School of Public Health, Xi\u2032an Jiaotong University Health Science Center  Xi\u2032an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06482-w"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2015-1106"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2008.01.004"},{"key":"e_1_2_8_5_1","volume-title":"China's health and family planning statistical yearbook 2018","author":"Commission NHAF","year":"2018"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2017.08.015"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2014.11.017"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25486"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2014.07.023"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-006-0690-3"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2018.08.017"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-311526"},{"issue":"2","key":"e_1_2_8_13_1","first-page":"609","article-title":"Changes in osteogenic gene expression in hypertrophic chondrocytes induced by SIN\u20101","volume":"16","author":"He Y.","year":"2018","journal-title":"Experimental and Therapeutic Medicine"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.01.005"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxj037"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.6506"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29196"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31020"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.133660"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.112"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199810153391604"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002640000216"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt684"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1987636"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000355"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2019.11.010"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.09.082"},{"issue":"7","key":"e_1_2_8_28_1","first-page":"539","article-title":"Exploring genome\u2010wide DNA methylation profiles altered in Kashin\u2010Beck disease using infinium human methylation 450 bead chips","volume":"29","author":"Shi X. W.","year":"2016","journal-title":"Biomedical and Environmental Sciences"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts680"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2019.07.014"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-019-01759-7"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2019.04.002"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2.9.1136"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.03.019"},{"key":"e_1_2_8_35_1","first-page":"36","article-title":"Study on the relations between Kashin\u2010Beck Disease and iodine","volume":"14","author":"Xu M. J.","year":"1999","journal-title":"Endemic Diseases Bulletin"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.633693"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000005669"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2002241"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.29809","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.29809","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.29809","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.29809","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T12:47:35Z","timestamp":1748350055000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.29809"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,27]]},"references-count":37,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1002\/jcp.29809"],"URL":"https:\/\/doi.org\/10.1002\/jcp.29809","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,27]]},"assertion":[{"value":"2020-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}