Reactive oxygen species induced-inhibition of odontoblastic differentiation of mouse dental papilla cells is mediated by downregulation of importin 7

Tooth dentin is a crucial tooth structure. The biological process of odontoblast differentiation is essential for formation of normal dentin. The accumulation of Reactive Oxygen Species (ROS) leads to oxidative stress, which can influence the differentiation of several cells. As a member of the Importin β-superfamily, importin 7 (IPO7) is essential for nucleocytoplasmic transport and plays an important role in the process of odontoblast differentiation and oxidative stress. Nevertheless, the association between ROS, IPO7, and odontoblast differentiation in mouse dental papilla cells (mDPCs) and the underlying mechanism remains to be elucidated. Here, we confirmed that ROS suppressed odontoblastic differentiation of mDPCs, as well as the expression and nucleocytoplasmic shuttle of IPO7 in cells, while overexpression of IPO7 can rescue these effects. ROS resulted in the increased phosphorylation of p38 and cytoplasmic aggregation of p-p38, which was able to be reversed by overexpression of IPO7. p-p38 interacted with IPO7 in mDPCs without treatment of H2O2, but with the presence of H2O2, the interaction between p-p38 and IPO7 was significantly decreased. Inhibition of IPO7 increased the expression level and the nuclear translocation of p53, which is mediated by cytoplasmic aggregation of p-p38. In conclusion, ROS inhibited odontoblastic differentiation of mouse dental papilla cells, which is mediated by downregulation and damaged nucleocytoplasmic shuttle of IPO7.