PFK activation is essential for the odontogenic differentiation of human dental pulp stem cells
PFK activation is essential for the odontogenic differentiation of human dental pulp stem cells
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PFK活性在人牙髓干细胞牙源性分化中的作用
DOI：
10.1016/j.bbrc.2021.01.059
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发表时间：
2021-01-29
影响因子：
3.1
通讯作者：
Lee, Jong-Ho
中科院分区：
文献类型：
--
作者：
Jeon, So Mi;Lim, Je Sun;Lee, Jong-Ho
牙髓干细胞（DPSC）可以分化为多种细胞系，包括负责牙本质形成的牙源性细胞，这在牙髓修复和牙齿再生中非常重要。虽然糖酵解在生理和病理条件下的各种细胞活动中起着核心作用，但其在牙源性分化中的作用和调控尚不清楚。在这里，我们发现有氧糖酵解诱导成牙本质细胞分化从人DPSCs。重要的是，我们证明，在成牙本质细胞分化，磷酸果糖激酶1肌肉亚型（PFKM）和PFK2，但不是其他糖酵解酶的蛋白质表达水平，主要上调AKT激活，导致总PFK酶活性增加。PFK活性的增加是促进有氧糖酵解的必要条件，而有氧糖酵解在人DPSCs向成牙本质细胞分化中起重要作用。这些发现强调PFK激活诱导的有氧糖酵解伴随并参与人DPSCs向牙源性谱系的分化，并且可能在牙髓修复的调节中发挥作用。(C)2021爱思唯尔公司All rights reserved.
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.