Effect of PI3K/AKT/FoxO1 signaling pathway on the proliferation and differentiation of dental papillae ecto-mesenchymal cells in ICR mice
LI Rui-min
LV Na
DING Xiao-yan
YAN Ya-mei
ZHANG Zhao-meng
Abstract：AIM:To explore the influence of the Phosphatidylinositide 3-kinase/protein kinase B/Forkhead box O1(PI3K/AKT/FoxO1)signaling pathway on the proliferation and osteogenic differentiation of dental papillae ecto-mesenchymal cells in ICR mice,and to provide a theoretical basis for a deeper understanding of the mechanism of tooth development and related diseases.METHODS:The expression of PI3K,AKT,FoxO1,and P21 proteins,which are the effectors of the PI3K/AKT/FoxO1 signaling pathway,in the dental germ tissues of ICR mice was detected by immunohistochemistry.dental papillae ecto-mesenchymal cells from ICR mice were cultured in vitro,and the PI3K/AKT/FoxO1 signaling pathway inhibitors were used for intervention,with different treatment groups set up.The changes in the proliferation activity and osteogenic differentiation ability of dental papillae ecto-mesenchymal cells were detected by CCK-8 and alizarin red staining experiments.RT-qPCR and Western Blot were used to detect the changes in osteogenic-related genes and the expression levels of genes related to the PI3K/AKT/FoxO1 signaling pathway in dental papillae ecto-mesenchymal cells.RESULTS:PI3K and AKT proteins were mainly expressed in the cytoplasm of ICR mouse dental germ cells,while FoxO1 and P21 proteins were expressed in the nuclei.In terms of cell proliferation,when the upstream of the PI3K/AKT/FoxO1 signaling pathway(PI3K)was inhibited,the expression of PI3K,AKT mRNA and protein all showed a downward trend,and the proliferation ability of dental papillae ecto-mesenchymal cells in ICR mice decreased.When the downstream of the signaling pathway(FoxO1)was inhibited,the expression of FoxO1 and P21 mRNA and protein all showed a downward trend,and the proliferation ability of dental papillae ecto-mesenchymal cells was promoted.In terms of osteogenic differentiation,when the PI3K/AKT/FoxO1 signaling pathway was inhibited,the formation of mineralized nodules in dental papillae ecto-mesenchymal cells of ICR mice increased,and the relative expression levels of osteogenic-related genes OCN,ALP mRNA and OCN protein increased,and their osteogenic differentiation ability was enhanced.The inhibition of the upstream of the signaling pathway(PI3K)had a more significant effect.CONCLUSION:The PI3K/AKT/FoxO1 signaling pathway plays a key regulatory role in the proliferation and osteogenic differentiation of dental papillae ecto-mesenchymal cells in ICR mice,providing potential targets and theoretical basis for the research and treatment of tooth development and related diseases.
Keywords：PI3K/AKT/FoxO1 signal pathwaydental papillae ecto-mesenchymal cellscell proliferationosteogenic differentiation
Publication Date：2025-06-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：8( 320-327 )