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However, the ferroptosis with orthodontic tooth movement(OTM) relationship has not been thoroughly described. We here analysed whether ferroptosis is involved in OTM\u2010associated alveolar bone loss. Mouse osteoblasts (MC\u20103T3) and knockdown glutathione peroxidase 4 (GPX4) MC\u20103T3 were stimulated with compressive force loading and ferrostatin\u20101 (Fer\u20101, a ferroptosis inhibitor), and the changes in lipid peroxidation morphology, expression of ferroptosis\u2010related factors and osteogenesis levels were detected. After establishing the rat experimental OTM model, the changes in ferroptosis\u2010related factors and osteogenesis levels were reevaluated in the same manner. Ferroptosis was involved in mechanical stress regulating osteoblast remodelling, and Fer\u20101 and erastin affected osteoblasts under compression force loading. Fer\u20101 regulated ferroptosis and autophagy in MC\u20103T3 and promoted bone proliferation. GPX4\u2010dependent ferroptosis stimulated the YAP (homologous oncoproteins Yes\u2010associated protein) pathway, and GPX4 promoted ferroptosis via the YAP\u2010TEAD (transcriptional enhanced associate domain) signal pathway under mechanical compression force. The in\u00a0vivo experiment results were consistent with the in\u00a0vitro experiment results. Ferroptosis transpires during the motion of orthodontic teeth, with compression force side occurring earlier than stretch side within 4\u2009h. GPX4 plays an important role in alveolar bone loss, while Fer\u20101 can inhibit the compression force\u2010side alveolar bone loss. GPX4's Hippo\u2010YAP pathway is activated by the lack of compression force in the lateral alveolar bone.<\/jats:p>","DOI":"10.1111\/jcmm.18231","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T02:49:05Z","timestamp":1710730145000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["<scp>GPX4<\/scp>\u2010mediated bone ferroptosis under mechanical stress decreased bone formation via the <scp>YAP\u2010TEAD<\/scp> signalling pathway"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6236-2056","authenticated-orcid":false,"given":"Wang","family":"Mengjia","sequence":"first","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Jun","sequence":"additional","affiliation":[{"name":"Department of Orthodontics Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang","family":"Jiahao","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7473-1015","authenticated-orcid":false,"given":"Guo","family":"Jie","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/bonekey.2012.102"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540601156188"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.48"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2014.35"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00077"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370216648805"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-015-3440-3"},{"issue":"1","key":"e_1_2_11_9_1","first-page":"19","article-title":"Progress and problems in bone and mineral disorders","volume":"13","author":"Gittoes N","year":"2017","journal-title":"Eur 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