{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:18:13Z","timestamp":1791001093363,"version":"4.1.0"},"reference-count":75,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:00:00Z","timestamp":1596758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG15768"],"award-info":[{"award-number":["AG15768"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG46927"],"award-info":[{"award-number":["AG46927"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000980","name":"Arthritis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000980","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007253","name":"Nancy Taylor Foundation for Chronic Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007253","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Osteoarthritis (OA) is a degenerative joint disease, and inflammation within an arthritic joint plays a critical role in disease progression. Pro\u2010inflammatory cytokines, specifically IL\u20101 and TNF\u2010\u03b1, induce aberrant expression of catabolic and degradative enzymes and inflammatory cytokines in OA and result in a challenging environment for cartilage repair and regeneration. MicroRNAs (miRNAS) are small noncoding RNAs and are important regulatory molecules that act by binding to target messenger RNAs (mRNAs) to reduce protein synthesis and have been implicated in many diseases, including OA. The goal of this study was to understand the mechanisms of miRNA regulation of the transcriptome of tissue\u2010engineered cartilage in response to IL\u20101\u03b2 and TNF\u2010\u03b1 using an in vitro murine induced pluripotent stem cell (miPSC) model system. We performed miRNA and mRNA sequencing to determine the temporal and dynamic responses of genes to specific inflammatory cytokines as well as miRNAs that are differentially expressed (DE) in response to both cytokines or exclusively to IL\u20101\u03b2 or TNF\u2010\u03b1. Through integration of mRNA and miRNA sequencing data, we created networks of miRNA\u2010mRNA interactions which may be controlling the response to inflammatory cytokines. Within the networks, hub miRNAs, miR\u201029b\u20103p, miR\u201017\u20105p, and miR\u201020a\u20105p, were identified. As validation of these findings, we found that delivery of miR\u201017\u20105p and miR\u201020a\u20105p mimics significantly decreased degradative enzyme activity levels while also decreasing expression of inflammation\u2010related genes in cytokine\u2010treated cells. This study utilized an integrative approach to determine the miRNA interactome controlling the response to inflammatory cytokines and novel mediators of inflammation\u2010driven degradation in tissue\u2010engineered cartilage.<\/jats:p>","DOI":"10.1096\/fj.202000889r","type":"journal-article","created":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T05:25:49Z","timestamp":1596777949000},"page":"11546-11561","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The miRNA\u2010mRNA interactome of murine induced pluripotent stem cell\u2010derived chondrocytes in response to inflammatory cytokines"],"prefix":"10.1096","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2563-220X","authenticated-orcid":false,"given":"Alison K.","family":"Ross","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Washington University St. Louis MO USA"},{"name":"Department of Biomedical Engineering Washington University St. Louis MO USA"},{"name":"Shriners Hospitals for Children St. Louis MO USA"},{"name":"Center of Regenerative Medicine Washington University St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7966-056X","authenticated-orcid":false,"given":"Rodrigo","family":"Coutinho de Almeida","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences Section Molecular Epidemiology Leiden University Medical Center Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1459-413X","authenticated-orcid":false,"given":"Yolande F. M.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences Section Molecular Epidemiology Leiden University Medical Center Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0528-5303","authenticated-orcid":false,"given":"Jiehan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Washington University St. Louis MO USA"},{"name":"Department of Biomedical Engineering Washington University St. Louis MO USA"},{"name":"Shriners Hospitals for Children St. Louis MO USA"},{"name":"Center of Regenerative Medicine Washington University St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7786-7081","authenticated-orcid":false,"given":"Ingrid","family":"Meulenbelt","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences Section Molecular Epidemiology Leiden University Medical Center Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7380-0330","authenticated-orcid":false,"given":"Farshid","family":"Guilak","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Washington University St. Louis MO USA"},{"name":"Department of Biomedical Engineering Washington University St. Louis MO USA"},{"name":"Shriners Hospitals for Children St. Louis MO USA"},{"name":"Center of Regenerative Medicine Washington University St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.22721"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.05240.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.196"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e328349c2b1"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-45803-8_5"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.08.045"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24352"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2011.12.009"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4591"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-009-0872-0"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.053272"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.03.022"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.03.073"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1601639113"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.016881"},{"key":"e_1_2_10_17_1","first-page":"S105","article-title":"TNF alpha and IL\u20101 beta are separate targets in chronic arthritis","volume":"17","author":"Joosten LA","year":"1999","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728214.2011.576670"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2015.03.004"},{"key":"e_1_2_10_20_1","first-page":"40","article-title":"The function of microRNAs in cartilage and osteoarthritis","volume":"37","author":"Swingler T","year":"2019","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.11005\/jbm.2016.23.3.121"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00045-5"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09267"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.08.028"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1372"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.162"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/03008207.2016.1208655"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707900105"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075012"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003740"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.10.002"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15388-4"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-213882"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1210422109"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38780"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2017.08.002"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.06.016"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2017.03.012"},{"key":"e_1_2_10_39_1","doi-asserted-by":"crossref","unstructured":"BolgerA GiorgiF.Trimmomatic: a flexible read trimming tool for illumina NGS data.2014.https:\/\/doi.org\/10.1093\/bioinformatics\/btu170.","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.14806\/ej.17.1.200"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1141"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05005"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1258"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1215"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-128"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"issue":"4","key":"e_1_2_10_50_1","article-title":"shiny: web application framework for R","volume":"1","author":"Chang W","year":"2019","journal-title":"R Package Version"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.81"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(86)90306-5"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.20538"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2018.07.012"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09335-6"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-212603"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054633"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2018.04.013"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.3109\/03008207.2015.1027340"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1699"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24404"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605298103"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2017.06.027"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-016-1939-4"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24678"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2012.0055"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep12775"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24745"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.05178-11"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23822"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000680"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-015-1374-z"},{"key":"e_1_2_10_73_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/9450240","article-title":"The MicroRNA Family Both in Normal Development and in Different Diseases: The miR\u201017\u201092 Cluster","volume":"2019","author":"Bai X","year":"2019","journal-title":"Biomed Res. Int"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.915"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00070"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201654"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1096%2Ffj.202000889R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202000889R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202000889R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202000889R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T21:18:57Z","timestamp":1761686337000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202000889R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,7]]},"references-count":75,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1096\/fj.202000889R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202000889r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,7]]},"assertion":[{"value":"2020-04-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}