{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:04:04Z","timestamp":1791475444160,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022MH215"],"award-info":[{"award-number":["ZR2022MH215"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2024QC169"],"award-info":[{"award-number":["ZR2024QC169"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthod Craniofacial Res"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Orthodontically induced inflammatory root resorption (OIIRR) is an inflammation induced by excessive orthodontic force in the periodontium. The aim of this study was to identify the role of ferroptosis in periodontal ligament cells in OIIRR and its underlying mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Human periodontal ligament cells (hPDLCs) were subjected to 2\u2009g\/cm<jats:sup>2<\/jats:sup> of compressive stress along with 20\u2009ng\/mL of interleukin\u20101\u03b2 (IL\u20101\u03b2) stimulation for 24\u2009h. The occurrence of ferroptosis in hPDLCs is detected by Western blot analysis and ferroptosis\u2010related kits. For in\u00a0vivo analyses, a mouse OIIRR model was established, and the ACSL4 inhibitor (Rosiglitazone, Rosi) was administered intraperitoneally. Micro\u2010CT was employed to evaluate the occurrence of OIIRR, and immunohistochemical staining (IHC) was performed to detect changes in ferroptosis\u2010related markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Upon applying compressive stress and IL\u20101\u03b2 stimulation to hPDLCs, Western blot analysis showed an upregulation of the ferroptosis marker ACSL4 and a downregulation of GPX4, along with significant increases in ROS, MDA and Fe<jats:sup>2+<\/jats:sup> levels, indicating enhanced ferroptosis. However, when hPDLCs were treated with Rosi (1\u2009\u03bcM), ferroptosis was alleviated. Micro\u2010CT analysis showed that root resorption volume decreased after Rosi application. Additionally, Ferroptosis\u2010related markers changed significantly in the PDLCs in mice via IHC staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ACSL4\u2010mediated ferroptosis, triggered by compressive stress and inflammation in hPDLCs, contributed to the development of OIIRR. Rosi has been shown to inhibit OIIRR and serve as a novel therapeutic target for OIIRR treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ocr.70002","type":"journal-article","created":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T05:18:26Z","timestamp":1751087906000},"page":"852-861","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Compressive Stress and Inflammation Induce Ferroptosis in Periodontal Ligament Cells Through <scp>ACSL4<\/scp> Activation in Orthodontically Induced Inflammatory Root Resorption"],"prefix":"10.1111","volume":"28","author":[{"given":"Liyan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Orthodontics The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"School of Stomatology Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"School of Stomatology Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runze","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"School of Stomatology Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Orthodontics The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"School of Stomatology Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9571-0958","authenticated-orcid":false,"given":"Chunmiao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"School of Stomatology Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejo\/cjz034"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.2319\/032112-240.1"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052388"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911405"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijos.2017.45"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2018.08.003"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2010.11.010"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13258"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.060257"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2020.09.006"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15092115"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109607"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2023.113612"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24129835"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/360438"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2020.03.014"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000002533"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1810918"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.08.124"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2002.17.2.210"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202402529"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034518759295"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2012.09.006"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2017.05.019"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.5149"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202001758R"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2020.04.001"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.18231"},{"issue":"2","key":"e_1_2_11_31_1","first-page":"180","article-title":"Orthodontically Induced Inflammatory Root Resorption. 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