{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:50:49Z","timestamp":1792691449781,"version":"4.5.0"},"reference-count":53,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370944"],"award-info":[{"award-number":["82370944"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Periodontitis development arises from the intricate interplay between bacterial biofilms and the host\u2019s immune response, where macrophages serve pivotal roles in defense and tissue homeostasis. Here, we uncover the mitigative effect of copper chelator Tetrathiomolybdate (TTM) on periodontitis through inhibiting cuproptosis, a newly identified form of cell death which is dependent on copper. Our study reveals concurrent cuproptosis and a macrophage marker within murine models. In response to lipopolysaccharide (LPS) stimulation, macrophages exhibit elevated cuproptosis-associated markers, which are mitigated by the administration of TTM. TTM treatment enhances autophagosome expression and mitophagy-related gene expression, countering the LPS-induced inhibition of autophagy flux. TTM also attenuates the LPS-induced fusion of autophagosomes and lysosomes, the degradation of lysosomal acidic environments, lysosomal membrane permeability increase, and cathepsin B secretion. In mice with periodontitis, TTM reduces cuproptosis, enhances autophagy flux, and decreases Ctsb levels. Our findings underscore the crucial role of copper-chelating agent TTM in regulating the cuproptosis\/mitophagy\/lysosome pathway during periodontitis inflammation, suggesting TTM as a promising approach to alleviate macrophage dysfunction. Modulating cuproptosis through TTM treatment holds potential for periodontitis intervention.<\/jats:p>","DOI":"10.3390\/ijms25115890","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T13:32:55Z","timestamp":1716903175000},"page":"5890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Copper Chelation Therapy Attenuates Periodontitis Inflammation through the Cuproptosis\/Autophagy\/Lysosome Axis"],"prefix":"10.3390","volume":"25","author":[{"given":"Lujin","family":"Zhang","sequence":"first","affiliation":[{"name":"Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Chen","family":"Tsai","sequence":"additional","affiliation":[{"name":"Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1702-6050","authenticated-orcid":false,"given":"Zihan","family":"Ni","sequence":"additional","affiliation":[{"name":"Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beichen","family":"Chen","sequence":"additional","affiliation":[{"name":"Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaiyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luhui","family":"Cai","sequence":"additional","affiliation":[{"name":"Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7448-6723","authenticated-orcid":false,"given":"Qiong","family":"Xu","sequence":"additional","affiliation":[{"name":"Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105375","DOI":"10.1016\/j.oraloncology.2021.105375","article-title":"Linking chronic periodontitis and oral cancer: A review","volume":"121","author":"Kavarthapu","year":"2021","journal-title":"Oral Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/prd.12221","article-title":"Periodontitis: Facts, fallacies and the future","volume":"75","author":"Slots","year":"2017","journal-title":"Periodontol. 2000"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/prd.12431","article-title":"Association between periodontitis and chronic kidney disease","volume":"89","author":"Parsegian","year":"2022","journal-title":"Periodontol. 2000"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1177\/0022034514552491","article-title":"Global Burden of Severe Periodontitis in 1990\u20132010: A Systematic Review and Metaregression","volume":"93","author":"Kassebaum","year":"2014","journal-title":"J. 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