Bilirubin reversibly affects cell death and odontogenic capacity in stem cells from human exfoliated deciduous teeth

H. Yamaza, E. Tomoda, S. Sonoda, K. Nonaka, T. Kukita, T. Yamaza

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Objective: 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-induced damage and suppression of deciduous tooth formation. In this study, we examined the effects of bilirubin in stem cells from human exfoliated deciduous teeth (SHED) in vitro. Materials and Methods: SHED were cultured under exposure to excess of bilirubin and then interruption of bilirubin stimulation. Results: Bilirubin induced cell death and inhibited the odontogenic capacity of SHED by suppressing AKT and extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathways and enhancing nuclear factor kappa B p65 (NF-κB p65) pathway. The interruption of bilirubin stimulation reduced cell death and recovered the inhibited odontogenic capacity of bilirubin-damaged SHED. The bilirubin interruption also normalized the impaired AKT, ERK1/2, and NF-κB p65 signaling pathways. Conclusion: These findings suggest that tooth hypodontia in patients with hyperbilirubinemia might be due to bilirubin-induced cell death and dentinogenic dysfunction of odontogenic stem cells via AKT, ERK1/2, and NF-κB pathways and also suggested that bilirubin-induced impairments in odontogenic stem cells were reversible when bilirubin stimulation is interrupted.

Original languageEnglish
Pages (from-to)809-819
Number of pages11
JournalOral Diseases
Issue number5
Publication statusPublished - Jul 2018

All Science Journal Classification (ASJC) codes

  • Otorhinolaryngology
  • Dentistry(all)


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