PFK activation is essential for the odontogenic differentiation of human dental pulp stem cells

Dental pulp stem cells (DPSCs) can differentiate into diverse cell lineages, including odontogenic cells that are responsible for dentin formation, which is important in pulp repair and tooth regeneration. While glycolysis plays a central role in various cellular activities in both physiological and pathological conditions, its role and regulation in odontogenic differentiation are unknown. Here, we show that aerobic glycolysis is induced during odontoblastic differentiation from human DPSCs. Importantly, we demonstrate that during odontoblastic differentiation, protein expression levels of phosphofructokinase 1 muscle isoform (PFKM) and PFK2, but not other glycolytic enzymes, are mainly upregulated by AKT activation, resulting in increased total PFK enzyme activity. Increased PFK activity is essential to enhance aerobic glycolysis, which plays an important role in the odontoblastic differentiation of human DPSCs. These findings underscore that PFK activation-induced aerobic glycolysis accompanies, and participates in, human DPSCs differentiation into odontogenic lineage, and could play a role in the regulation of dental pulp repair. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

The study demonstrates that aerobic glycolysis is induced during odontoblastic differentiation from human DPSCs, with upregulation of protein expression levels of PFKM and PFK2 mainly mediated by AKT activation. This increased PFK activity is essential for enhancing aerobic glycolysis, which plays a crucial role in odontoblastic differentiation of human DPSCs. These findings suggest that PFK activation-induced aerobic glycolysis accompanies and participates in the differentiation of human DPSCs into odontogenic lineage, potentially influencing dental pulp repair.