{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T20:38:33Z","timestamp":1780087113867,"version":"3.54.0"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T00:00:00Z","timestamp":1511136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K11836"],"award-info":[{"award-number":["16K11836"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Dental calculus is a mineralized deposit attached to the tooth surface. We have shown that cellular uptake of dental calculus triggers nucleotide\u2010binding oligomerization domain\u2010like receptor family pyrin domain\u2010containing 3 (<jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3) inflammasome activation, leading to the processing of the interleukin\u20101\u03b2 precursor into its mature form in mouse and human phagocytes. The activation of the <jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3 inflammasome also induced a lytic form of programmed cell death, pyroptosis, in these cells. However, the effects of dental calculus on other cell types in periodontal tissue have not been investigated. The aim of this study was to determine whether dental calculus can induce cell death in oral epithelial cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\u20102 human oral squamous carcinoma cells, <jats:styled-content style=\"fixed-case\">HOMK<\/jats:styled-content>107 human primary oral epithelial cells and immortalized mouse macrophages were exposed to dental calculus or 1 of its components, hydroxyapatite crystals. For inhibition assays, the cells were exposed to dental calculus in the presence or absence of cytochalasin D (endocytosis inhibitor), z\u2010<jats:styled-content style=\"fixed-case\">YVAD<\/jats:styled-content>\u2010fmk (caspase\u20101 inhibitor) or glyburide (<jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3 inflammasome inhibitor). Cytotoxicity was determined by measuring lactate dehydrogenase (<jats:styled-content style=\"fixed-case\">LDH<\/jats:styled-content>) release and staining with propidium iodide. Tumor necrosis factor\u2010\u03b1 production was quantified by enzyme\u2010linked immunosorbent assay. Oral epithelial barrier function was examined by permeability assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Dental calculus induced cell death in <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\u20102 cells, as judged by <jats:styled-content style=\"fixed-case\">LDH<\/jats:styled-content> release and <jats:styled-content style=\"fixed-case\">propidium iodide<\/jats:styled-content> staining. Dental calculus also induced <jats:styled-content style=\"fixed-case\">LDH<\/jats:styled-content> release from <jats:styled-content style=\"fixed-case\">HOMK<\/jats:styled-content>107 cells. Following heat treatment, dental calculus lost its capacity to induce tumor necrosis factor\u2010\u03b1 in mouse macrophages, but could induce <jats:styled-content style=\"fixed-case\">LDH<\/jats:styled-content> release in <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\u20102 cells, indicating a major role of inorganic components in cell death. Hydroxyapatite crystals also induced cell death in both <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\u20102 and <jats:styled-content style=\"fixed-case\">HOMK<\/jats:styled-content>107 cells, as judged by <jats:styled-content style=\"fixed-case\">LDH<\/jats:styled-content> release, indicating the capacity of crystal particles to induce cell death. Cell death induced by dental calculus was significantly inhibited by cytochalasin D, z\u2010<jats:styled-content style=\"fixed-case\">YVAD<\/jats:styled-content>\u2010fmk and glyburide, indicating <jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3 inflammasome involvement. In permeability assays, dental calculus attenuated the barrier function of <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\u20102 cell monolayers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Dental calculus induces pyroptotic cell death in human oral epithelial cells and the crystalline structure plays a major role in this process. Oral epithelial cell death induced by dental calculus might be important for the etiology of periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12520","type":"journal-article","created":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T04:16:46Z","timestamp":1511237806000},"page":"353-361","source":"Crossref","is-referenced-by-count":22,"title":["Crystalline structure of pulverized dental calculus induces cell death in oral epithelial cells"],"prefix":"10.1111","volume":"53","author":[{"given":"S. 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