{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:33:49Z","timestamp":1787027629083,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T00:00:00Z","timestamp":1667865600000},"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":["U20A20365"],"award-info":[{"award-number":["U20A20365"]}],"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":["81970948"],"award-info":[{"award-number":["81970948"]}],"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":["2022NSFSC0613"],"award-info":[{"award-number":["2022NSFSC0613"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Sichuan Province of China","award":["U20A20365"],"award-info":[{"award-number":["U20A20365"]}]},{"name":"Natural Science Foundation of Sichuan Province of China","award":["81970948"],"award-info":[{"award-number":["81970948"]}]},{"name":"Natural Science Foundation of Sichuan Province of China","award":["2022NSFSC0613"],"award-info":[{"award-number":["2022NSFSC0613"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The study was to investigate the effect of canonical and noncanonical pyroptosis in apical periodontitis. Proteins\u2019 profiles of human apical periodontitis tissue were analyzed by label-free proteomics. Immunofluorescence was used to detect proteins related to pyroptosis in human apical periodontitis tissues and experimental apical periodontitis models. A dual experimental apical periodontitis model with both smaller (mandible) and larger (maxilla) bone lesions was established. THP-1-derived macrophages were stimulated with P. gingivalis lipopolysaccharide in vitro with or without the caspase-1\/-4\/-5 inhibitor Ac-FTDL-CMK. Propidium iodide staining, lactic dehydrogenase release and Western blot were applied to evaluate cell death and the protein expression. Caspase-1\/-4\/-5 were expressed in human apical periodontitis tissues. Caspase-1\/-11 were involved in bone loss in experimental apical periodontitis. Caspase-1\/-11 inhibitors reduced bone loss in larger lesions (maxilla) but accelerated bone loss in smaller lesions (mandible). Caspase-1\/-4\/-5 inhibitors also showed double-edged sword effects on propidium iodide staining and lactic dehydrogenase release in vitro. The expression of cleaved-caspase-1\/-4\/-5, mature interluekin-1\u03b2 and gasdermin D N-terminal domain increased in THP-1-derived macrophages after lipopolysaccharide stimulation but decreased after treatment with Ac-FTDL-CMK. Pyroptosis contributed to apical periodontitis and excited a double-edged sword effect in inducing bone loss in vivo and cell death in vitro.<\/jats:p>","DOI":"10.3390\/biom12111660","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T02:34:52Z","timestamp":1667961292000},"page":"1660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Double-Edged Sword Effect of Pyroptosis: The Role of Caspase-1\/-4\/-5\/-11 in Different Levels of Apical Periodontitis"],"prefix":"10.3390","volume":"12","author":[{"given":"Zhiwu","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Ren","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Cheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5590-3395","authenticated-orcid":false,"given":"Ran","family":"Cheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1111\/iej.12507","article-title":"Endodontic medicine: Connections between apical periodontitis and systemic diseases","volume":"48","year":"2015","journal-title":"Int. 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