The GLUT1-mTORC1 axis affects odontogenic differentiation of human dental pulp stem cells

Human dental pulp stem cells (hDPSCs) are considered valuable for regenerative therapy. Although glucose transporter 1 (GLUT1) is known to play a critical role in cell differentiation, its mechanism of the odontogenic differentiation of hDPSCs remains unclear. This study was conducted to investigate the effect and underlying mechanisms of GLUT1 on odontogenic differentiation of hDPSCs. hDPSCs was treated with phloretin (Phl), a GLUT1 inhibitor. The impact of GLUT1 on the odontogenic differentiation of hDPSCs was analysed using quantitative real-time polymerase chain reaction, alizarin-red staining, and western blotting. Glucose uptake by hDPSCs was significantly inhibited by Phl treatment. Overall, inhibition of GLUT1 upregulated the expression of DSPP, DMP1, RUNX2, and OCN and increased the formation of mineralised nodules on odontogenic induction of hDPSCs. The levels of phosphorylated mTOR and ribosomal protein S6 kinase 1 (p70S6K) were increased after GLUT1 inhibition and decreased by an mTOR inhibitor (rapamycin, Rapa) during the odontogenic induction of hDPSCs. Moreover, mTOR suppression decreased the expression of the genes described above and formation of mineralised nodules. These results suggest that inhibition of GLUT1 promoted the odontogenic differentiation of hDPSCs via the mTORC1-p70S6K axis, providing a foundation for further application of hDPSCs in regenerative therapy.