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Accumulating human evidence firmly implicates pyroptosis in the pathogenesis of major oral and maxillofacial diseases, with cleaved gasdermin D (GSDMD)\/gasdermin E (GSDME) detected in clinical specimens of periodontitis, peri-implantitis, apical periodontitis, oral lichen planus, and oral submucous fibrosis. The central mechanism involves inflammasome assembly (eg, NLRP3), leading to caspase activation, gasdermin cleavage (eg, GSDMD, GSDME), and consequent pyroptotic cell lysis. Functional in vivo studies establish a direct causal link: genetic ablation of caspase-1 attenuates alveolar bone loss in murine periodontitis models, while pharmacologic inhibition of NLRP3 mitigates fibrosis and slows disease progression in rat models of oral submucous fibrosis by suppressing pyroptosis. In peri-implantitis, NLRP3 suppression inhibits macrophage pyroptosis and promotes osteogenesis. Similarly, the activation of GSDMD and GSDME is shown to trigger pyroptosis and exacerbate pulpal and periapical inflammation in apical periodontitis models. Conversely, in oral squamous cell carcinoma, pyroptosis induction potently stimulates anti-tumor immunity. This context-dependent duality of pyroptosis provides the rationale for precision medicine. Emerging strategies reflecting this approach include cell-based therapies using dental pulp stem cells to alleviate pyroptosis and promote nerve regeneration in macaque models as well as advanced nanomaterials such as angiopoietin-coupled carbon nanotubes that modulate pyroptosis-related pathways to enhance bone regeneration in rabbits. Collectively, these insights position the precise modulation of pyroptosis as a new frontier in the management of oral and maxillofacial diseases.<\/jats:p>","DOI":"10.1177\/00220345261443990","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T06:59:17Z","timestamp":1779865157000},"page":"982-993","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting Pyroptosis in Oral and Maxillofacial Diseases"],"prefix":"10.1177","volume":"105","author":[{"given":"L.","family":"Tang","sequence":"first","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Wang","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Yu","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Chai","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Chen","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Yang","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China"},{"name":"Department of Implantology, The Affiliated Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0212-9305","authenticated-orcid":false,"given":"T.","family":"Huang","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China"},{"name":"Department of Implantology, The Affiliated Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"crossref","unstructured":"Booty LM Bryant CE. 2022. 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