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Bilirubin reversibly affects cell death and odontogenic capacity in stem cells from human exfoliated deciduous teeth
Author(s) -
Yamaza H,
Tomoda E,
Sonoda S,
aka K,
Kukita T,
Yamaza T
Publication year - 2018
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/odi.12827
Subject(s) - deciduous teeth , bilirubin , stem cell , medicine , protein kinase b , programmed cell death , microbiology and biotechnology , pathology , biology , dentistry , signal transduction , biochemistry , apoptosis
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 ( ERK 1/2) 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 , ERK 1/2, 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 , ERK 1/2, and NF ‐κB pathways and also suggested that bilirubin‐induced impairments in odontogenic stem cells were reversible when bilirubin stimulation is interrupted.