{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:03:26Z","timestamp":1789553006085,"version":"build-2803163510"},"reference-count":59,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470963"],"award-info":[{"award-number":["82470963"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82401079"],"award-info":[{"award-number":["82401079"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Apical periodontitis (AP) is an infectious disorder characterized by periapical inflammation and alveolar bone destruction. Recent evidence suggests that cuproptosis, a distinctive form of copper\u2010regulated cell death, has been implicated in the regulation of bone loss. This study aimed to investigate the involvement of cuproptosis and its mechanism in modulating bone loss in AP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>Periapical specimens from healthy subjects or AP patients were collected to evaluate copper content and the expression level of cuproptosis\u2010associated proteins. Single\u2010cell RNA sequencing (scRNA\u2010seq) datasets (GSE171213, GSE181688, and GSE197680) were re\u2010analysed to identify the specific cell types undergoing cuproptosis. An AP rat model was constructed and treated with the copper chelator tetrathiomolybdate (TTM). Alveolar bone loss was assessed using micro\u2010CT, H&amp;E staining, copper ion staining, and immunohistochemistry. In\u00a0vitro, jaw bone marrow mesenchymal stem cells (JBMMSCs) were stimulated with lipopolysaccharide (LPS) or cuproptosis inducer (Elesclomol\u2010Cu) to mimic the AP microenvironment. The effects of TTM on osteogenic differentiation were examined via qRT\u2010PCR, Western blotting, ALP staining, and ARS staining. LC\u2013MS\/MS proteomics was utilized to explore the mechanism by which TTM attenuates bone loss. Moreover, cuproptotic JBMMSCs were treated with JY\u20102 (FoxO inhibitor) to determine whether cuproptosis aggravates osteogenic dysfunction via the FoxO\/\u03b2\u2010catenin axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Copper concentrations were significantly elevated in human and rat AP tissues compared with healthy tissues. Analysis of scRNA\u2010seq data revealed that cuproptosis predominantly occurred in JBMMSCs. In the rat model, TTM administration significantly alleviated alveolar bone loss by reducing cuproptosis in JBMMSCs. Furthermore, JBMMSCs stimulated with LPS or Elesclomol\u2010Cu exhibited characteristics of cuproptosis and impaired osteogenic function. TTM treatment markedly reduced cuproptosis and restored osteogenic capacity. Mechanistically, cuproptosis in JBMMSCs led to the dephosphorylation of FoxOs. Conversely, TTM reversed these changes both in\u00a0vivo and in\u00a0vitro. Furthermore, inhibition of FoxO signalling with JY\u20102 disrupted FoxO3\/\u03b2\u2010catenin interaction, enhanced \u03b2\u2010catenin expression and rescued the osteogenic dysfunction induced by cuproptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cuproptosis acts as a novel driver of alveolar bone loss in AP by impairing the osteogenic potential of JBMMSCs. TTM targeting cuproptosis represents a promising strategy to attenuate bone resorption in AP by the cuproptosis\/FoxO\/\u03b2\u2010catenin pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.70266","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:14:25Z","timestamp":1789550065000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of Jaw Bone Marrow Mesenchymal Stem Cell Cuproptosis Attenuates Bone Loss in Apical Periodontitis via Suppressing the\n                    <scp>FoxO<\/scp>\n                    Signalling Pathway"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3079-1777","authenticated-orcid":false,"given":"Kaiying","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Endodontics, Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou 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