{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T13:13:36Z","timestamp":1792502016800,"version":"4.5.0"},"reference-count":55,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T00:00:00Z","timestamp":1668124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000142","name":"Arthritis Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000142","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","award":["225404"],"award-info":[{"award-number":["225404"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","award":["30865"],"award-info":[{"award-number":["30865"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","award":["36349"],"award-info":[{"award-number":["36349"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["203475"],"award-info":[{"award-number":["203475"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006538","name":"Canadian Arthritis Network","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006538","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Synovial fibrosis contributes to osteoarthritis (OA) pathology, but the underlying mechanisms remain unknown. We have observed increased microRNA\u201027b\u20103p (miR\u201027b\u20103p) levels in synovial fluid of patients with late\u2010stage radiographic knee OA. Here, we investigated the contribution of miR\u201027b\u20103p to synovial fibrosis in patients with severe knee OA and in a mouse model of knee OA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We stained synovium sections obtained from patients with radiographic knee OA scored according to the Kellgren\/Lawrence scale and mice that underwent destabilization of the medial meniscus (DMM) for miR\u201027b\u20103p using in situ hybridization. We examined the effects of intraarticular injection of miR\u201027b\u20103p mimic into naive mouse knee joints and intraarticular injection of a miR\u201027b\u20103p inhibitor into mouse knee joints after DMM. We performed transfection with miR\u201027b\u20103p mimic and miR\u201027b\u20103p inhibitor in human OA fibroblast\u2010like synoviocytes (FLS) using reverse transcriptase\u2013quantitative polymerase chain reaction (RT\u2010qPCR) array, RNA sequencing, RT\u2010qPCR, Western blotting, immunofluorescence, and migration assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed increased miR\u201027b\u20103p expression in the synovium from patients with knee OA and in mice with DMM\u2010induced arthritis. Injection of the miR\u201027b\u20103p mimic in mouse knee joints induced a synovial fibrosis\u2010like phenotype, increased synovitis scores, and increased COL1A1 and \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) expression. In the mouse model of DMM\u2010induced arthritis, injection of the miR\u201027b\u20103p inhibitor decreased \u03b1\u2010SMA but did not change COL1A1 expression levels or synovitis scores. Transfection with the miR\u201027b\u20103p mimic in human OA FLS induced profibrotic responses, including increased migration and expression of key extracellular matrix (ECM) genes, but transfection with the miR\u201027b\u20103p inhibitor had the opposite effects. RNA sequencing identified a PPARG\/ADAMTS8 signaling axis regulated by miR\u201027b\u20103p in OA FLS. Human OA FLS transfected with miR\u201027b\u20103p mimic and then treated with the PPARG agonist rosiglitazone or with ADAMTS8 small interfering RNA exhibited altered expression of select ECM genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings demonstrate that miR\u201027b\u20103p has a key role in ECM regulation associated with synovial fibrosis during OA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42285","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T07:30:39Z","timestamp":1657092639000},"page":"1928-1942","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Contribution of <scp>MicroRNA<\/scp>\u201027b\u20103p to Synovial Fibrotic Responses in Knee Osteoarthritis"],"prefix":"10.1002","volume":"74","author":[{"given":"Ghazaleh","family":"Tavallaee","sequence":"first","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Krembil Research Institute, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Starlee","family":"Lively","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, and Krembil Research Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason S.","family":"Rockel","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, and Krembil Research Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabana Amanda","family":"Ali","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada, and Bone &amp; Joint Center, Department of Orthopaedic Surgery, Henry Ford Health System  Detroit Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Im","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clementine","family":"Sarda","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, and Krembil Research Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greniqueca M.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, and Krembil Research Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny","family":"Rossomacha","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, and Krembil Research Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayaka","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, and Krembil Research Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratibha","family":"Potla","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, and Krembil Research Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Gabrial","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, and Krembil Research Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Matelski","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, and Krembil Research Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anusha","family":"Ratneswaran","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, and Krembil Research Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Perry","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, and Krembil Research Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Hinz","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, University of Toronto, and Laboratory of Tissue Repair and Regeneration, Keenan Research Centre for Biomedical Science of the St. Michael's Hospital  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Krembil Research Institute, University Health Network, and Departments of Medical Biophysics and Computer Science, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Jurisica","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Krembil Research Institute, University Health Network, Toronto, Departments of Medical Biophysics and Computer Science, University of Toronto, Toronto, Ontario, Canada, and Institute of Neuroimmunology, Slovak Academy of Sciences  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9877-0772","authenticated-orcid":false,"given":"Mohit","family":"Kapoor","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Krembil Research Institute, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, and Division of Orthopaedic Surgery, Department of Surgery, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.03.018"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.09.013"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.02.012"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.12939"},{"key":"e_1_2_7_6_1","article-title":"The role of fibrosis in osteoarthritis progression","volume":"11","author":"Rim YA","year":"2020","journal-title":"Life (Basel)"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-017-1229-9"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.121630"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells7080092"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.00376"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.684389"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2016.04.019"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2007.03.006"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.05.025"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ocarto.2020.100131"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1144"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1037"},{"key":"e_1_2_7_19_1","first-page":"D479","article-title":"pathDIP 4: an extended pathway annotations and enrichment analysis resource for human, model organisms and domesticated species","volume":"48","author":"Rahmati S","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp595"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/21691401.2019.1607362"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27329"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24761"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.9.2730"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12971"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2019.03.039"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-020-02207-x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e17-03-0134"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-020-01669-w"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1134\/S0006297916060055"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.11394"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12340471"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155412436586"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21145154"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-1249"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-020-09886-7"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvv098"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.12.005"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40568"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02717-7"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-71749-6"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr037"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.17352"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.315398"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/2379280"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14211"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2015-0205OC"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578-020-0213-1"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000027183"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13076"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.01371"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.066399"},{"key":"e_1_2_7_53_1","first-page":"1358","article-title":"Peroxisome proliferator\u2010activated receptor\u2010\u03b3 agonist inhibits collagen synthesis in human keloid fibroblasts by suppression of early growth response\u20101 expression through upregulation of miR\u2010543 expression","volume":"6","author":"Zhu HY","year":"2016","journal-title":"Am J Cancer Res"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.3892\/br.2016.708"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-401-8_24"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-004-0545-y"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.42285","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.42285","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.42285","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T20:16:22Z","timestamp":1759954582000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.42285"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,11]]},"references-count":55,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/art.42285"],"URL":"https:\/\/doi.org\/10.1002\/art.42285","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,11]]},"assertion":[{"value":"2021-06-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}