Department of Pediatric Dentistry, Kyushu University Graduate School of Dental Science, Fukuoka, Japan.
Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka, Japan.
Oral Dis. 2018 Jul;24(5):809-819. doi: 10.1111/odi.12827. Epub 2018 Apr 17.
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.
SHED were cultured under exposure to excess of bilirubin and then interruption of bilirubin stimulation.
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.
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.
胆道闭锁患者的高胆红素血症可导致乳牙损伤，如绿素沉着和牙本质发育不全。在接受肝移植的胆道闭锁患者中，牙齿结构在影像学上似乎得到了恢复。然而，人们对胆红素诱导损伤和抑制乳牙形成的细胞机制知之甚少。在这项研究中，我们研究了胆红素对人脱落乳牙干细胞（SHED）的体外作用。
SHED 在暴露于过量胆红素和随后中断胆红素刺激的情况下进行培养。
胆红素诱导细胞死亡，并通过抑制 AKT 和细胞外信号调节激酶 1 和 2（ERK1/2）通路和增强核因子 kappa B p65（NF-κB p65）通路来抑制 SHED 的成牙能力。中断胆红素刺激可减少细胞死亡并恢复胆红素损伤 SHED 抑制的成牙能力。胆红素中断还使受损的 AKT、ERK1/2 和 NF-κB p65 信号通路正常化。
这些发现表明，高胆红素血症患者的牙齿缺失可能是由于胆红素通过 AKT、ERK1/2 和 NF-κB 通路诱导细胞死亡和牙源性干细胞的牙本质功能障碍所致，并且当中断胆红素刺激时，牙源性干细胞的胆红素诱导损伤是可逆的。
