{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:13:53Z","timestamp":1780359233914,"version":"3.54.1"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,6]],"date-time":"2023-05-06T00:00:00Z","timestamp":1683331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970923"],"award-info":[{"award-number":["81970923"]}],"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":["82170944"],"award-info":[{"award-number":["82170944"]}],"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":["U22A20313"],"award-info":[{"award-number":["U22A20313"]}],"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":["81970904"],"award-info":[{"award-number":["81970904"]}],"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"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Pyroptosis is a type of inflammatory cell death and is related to pulpitis and apical periodontitis. In this study, the aim was to investigate how periodontal ligament fibroblasts (PDLFs) and dental pulp cells (DPCs) respond to pyroptotic stimuli and explore whether dimethyl fumarate (DMF) could block pyroptosis in PDLFs and DPCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>Three methods (stimulation with lipopolysaccharide [LPS] plus nigericin, poly(dA:dT) transfection and LPS transfection) were used to induce pyroptosis in PDLFs and DPCs, two types of fibroblasts related to pulpitis and apical periodontitis. THP\u20101 cell was used as a positive control. Afterwards, PDLFs and DPCs were treated with or without DMF before inducing pyroptosis to examine the inhibitory effect of DMF. Pyroptotic cell death was measured by lactic dehydrogenase (LDH) release assays, cell viability assays, propidium iodide (PI) staining and flow cytometry. The expression levels of cleaved gasdermin D N\u2010terminal (GSDMD NT), caspase\u20101 p20, caspase\u20104 p31 and cleaved PARP were examined by immunoblotting. Immunofluorescence analysis was used to detect the cellular distribution of GSDMD NT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Periodontal ligament fibroblasts and DPCs were more sensitive to cytoplasmic LPS\u2010induced noncanonical pyroptosis than to canonical pyroptosis induced by stimulation with LPS priming plus nigericin or by poly(dA:dT) transfection. In addition, treatment with DMF attenuated cytoplasmic LPS\u2010induced pyroptotic cell death in PDLFs and DPCs. Mechanistically, it was shown that the expression and plasma membrane translocation of GSDMD NT were inhibited in DMF\u2010treated PDLFs and DPCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study indicates that PDLFs and DPCs are more sensitive to cytoplasmic LPS\u2010induced noncanonical pyroptosis and that DMF treatment blocks pyroptosis in LPS\u2010transfected PDLFs and DPCs by targeting GSDMD, suggesting DMF might be a promising drug for the management of pulpitis and apical periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.13926","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T10:34:17Z","timestamp":1682591657000},"page":"869-880","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The effects of dimethyl fumarate on cytoplasmic LPS\u2010induced noncanonical pyroptosis in periodontal ligament fibroblasts and dental pulp cells"],"prefix":"10.1111","volume":"56","author":[{"given":"Fan","family":"Gu","sequence":"first","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) &amp; Key Laboratory of Oral Biomedicine Ministry of Education, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailin","family":"Wu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) &amp; Key Laboratory of Oral Biomedicine Ministry of Education, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Huang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) &amp; Key Laboratory of Oral Biomedicine Ministry of Education, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) &amp; Key Laboratory of Oral Biomedicine Ministry of Education, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihuan","family":"Yang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) &amp; Key Laboratory of Oral Biomedicine Ministry of Education, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuan","family":"Bian","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) &amp; Key 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