{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T01:32:57Z","timestamp":1789003977263,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T00:00:00Z","timestamp":1523923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Grants-in-Aid for Scientific Research (C)","award":["16K11806"],"award-info":[{"award-number":["16K11806"]}]},{"name":"Grants-in-Aid for Scientific Research (B)","award":["25293405"],"award-info":[{"award-number":["25293405"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Hyperbilirubinemia in patients with biliary atresia causes deciduous tooth injuries such as green pigmentation and dentin hypoplasia. In patients with biliary atresia who received liver transplantation, tooth structure appears to be recovered radiographically. Nevertheless, little is known about cellular mechanisms underlying bilirubin\u2010induced damage and suppression of deciduous tooth formation. In this study, we examined the effects of bilirubin in stem cells from human exfoliated deciduous teeth (<jats:styled-content style=\"fixed-case\">SHED<\/jats:styled-content>) in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">SHED<\/jats:styled-content> were cultured under exposure to excess of bilirubin and then interruption of bilirubin stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bilirubin induced cell death and inhibited the odontogenic capacity of <jats:styled-content style=\"fixed-case\">SHED<\/jats:styled-content> by suppressing <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content> and extracellular signal\u2010regulated kinase 1 and 2 (<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2) pathways and enhancing nuclear factor kappa B p65 (<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB p65) pathway. The interruption of bilirubin stimulation reduced cell death and recovered the inhibited odontogenic capacity of bilirubin\u2010damaged <jats:styled-content style=\"fixed-case\">SHED<\/jats:styled-content>. The bilirubin interruption also normalized the impaired <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> ERK<\/jats:styled-content>1\/2, and <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB p65 signaling pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest that tooth hypodontia in patients with hyperbilirubinemia might be due to bilirubin\u2010induced cell death and dentinogenic dysfunction of odontogenic stem cells via <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> ERK<\/jats:styled-content>1\/2, and <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB pathways and also suggested that bilirubin\u2010induced impairments in odontogenic stem cells were reversible when bilirubin stimulation is interrupted.<\/jats:p><\/jats:sec>","DOI":"10.1111\/odi.12827","type":"journal-article","created":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T12:24:49Z","timestamp":1515587089000},"page":"809-819","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Bilirubin reversibly affects cell death and odontogenic capacity in stem cells from human exfoliated deciduous teeth"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1138-3943","authenticated-orcid":false,"given":"H","family":"Yamaza","sequence":"first","affiliation":[{"name":"Department of Pediatric Dentistry Kyushu University Graduate School of Dental Science  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Tomoda","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry Kyushu University Graduate School of Dental Science  Fukuoka Japan"},{"name":"Department of Molecular Cell Biology and Oral Anatomy Kyushu University Graduate School of Dental Science  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Sonoda","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology and Oral Anatomy Kyushu University Graduate School of Dental Science  Fukuoka Japan"},{"name":"Research fellow of Japan Society for the Promotion of Science  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Nonaka","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry Kyushu University Graduate School of Dental Science  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Kukita","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology and Oral Anatomy Kyushu University Graduate School of Dental Science  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Yamaza","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology and Oral Anatomy Kyushu University Graduate School of Dental Science  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,17]]},"reference":[{"issue":"4","key":"e_1_2_8_2_1","first-page":"322","article-title":"Oral and systemic findings in biliary atresia: Report of 11 cases","volume":"4","author":"Belanger G. 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