{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:30:22Z","timestamp":1792150222514,"version":"4.4.0"},"reference-count":15,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U2CAG088071"],"award-info":[{"award-number":["U2CAG088071"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ACR Open Rheumatology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Juvenile dermatomyositis (JDM) involves up\u2010regulated type I interferons (IFNs), including IFN\u03b2, yet pathologic mechanisms remain poorly understood. We aimed to characterize the functional and structural effects of IFN\u03b2 on in vitro human pediatric myoblast growth and differentiation in a three\u2010dimensional skeletal muscle model (myobundles).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Myobundles fabricated from myoblasts of a healthy pediatric donor were exposed to IFN\u03b2 at 0 to 5,600 IU\/mL during growth (days 1\u20134), differentiation (days 4\u201311), and\/or mature (days 11\u201318) periods. To assess myobundle structure and function, contractile force, kinetics, and fatigue were measured at day 18 with subsequent immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Myobundles were not functionally affected by IFN\u03b2 exposure during growth period alone. However, when IFN\u03b2 exposure continued through differentiation, myobundles became dysfunctional (<jats:italic>P<\/jats:italic> &lt; 0.0001). IFN\u03b2 during differentiation or mature periods alone resulted in dose\u2010dependent decreases in contractility, with greater decrease in the differentiation alone group (<jats:italic>P<\/jats:italic> &lt; 0.0001). Twitch kinetics and fatigue remained largely unchanged when myobundles were exposed to IFN\u03b2 only during growth, yet twitch time slowed (<jats:italic>P<\/jats:italic> &lt; 0.005) and fatigue decreased (<jats:italic>P<\/jats:italic> &lt; 0.002) when myobundles were exposed during differentiation or mature stages alone. Nuclei density and myofiber size and organization also decreased when IFN\u03b2 was added during differentiation period alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>IFN\u03b2 decreases pediatric myobundle contractile function most significantly during differentiation of myoblasts to myotubes. Function is not affected when IFN\u03b2 exposure is limited to myoblast proliferation alone. These findings implicate a pathologic role for IFN\u03b2 in JDM by impairing myoblast differentiation, leading to subsequent loss of function and ongoing need for muscle regeneration and repair.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr2.11760","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:35:15Z","timestamp":1729643715000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Interferon\u2010\u03b2\u2013Induced Injury During Pediatric Muscle Differentiation: Insight Into Juvenile Dermatomyositis Pathogenesis"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1362-5635","authenticated-orcid":false,"given":"Lauren T.","family":"Covert","sequence":"first","affiliation":[{"name":"Duke University Health System  Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Osman","sequence":"additional","affiliation":[{"name":"Duke University  Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Truskey","sequence":"additional","affiliation":[{"name":"Duke University  Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.4078\/jrd.2022.29.1.14"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-005-0048-1"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40800"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3531"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.04885"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.3266"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead186"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23012"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keae082"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065362"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy105"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200271"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121508"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2018.09.002"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-216599"}],"container-title":["ACR Open Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acr2.11760","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T15:25:37Z","timestamp":1759418737000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/acr2.11760"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,22]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/acr2.11760"],"URL":"https:\/\/doi.org\/10.1002\/acr2.11760","archive":["Portico"],"relation":{},"ISSN":["2578-5745","2578-5745"],"issn-type":[{"value":"2578-5745","type":"print"},{"value":"2578-5745","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,22]]},"assertion":[{"value":"2024-07-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e11760"}}