a Department of Stomatology, Nanfang Hospital, Southern Medical University , Guangzhou , China.
b Department of Medical Genetics, School of Basic Medicine Sciences, Southern Medical University , Guangzhou , China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2575-2584. doi: 10.1080/21691401.2019.1629950.
Our previous studies have revealed that a dominant mutation in vacuolar protein sorting 4B (VPS4B), a member of the AAA ATPase family, causes dentin dysplasia type I. The purpose of the present study was to investigate the roles of VPS4B in human dental pulp stem cells (hDPSCs) and to elucidate the underlying molecular mechanisms. In this study, we found that VPS4B was highly expressed in the dental pulp cells of the mouse molar tooth germ, and the expression of VPS4B increased significantly during the odontoblastic differentiation of hDPSCs. VPS4B downregulation inhibited the proliferation, migration, and odontoblastic differentiation of hDPSCs. Moreover, treatment with lithium chloride, an agonist of the Wnt-β-catenin signalling pathway, partially reversed the VPS4B knockdown-driven suppression of proliferation and of odontoblastic differentiation of hDPSCs. Collectively, our findings indicate that VPS4B, via Wnt-β-catenin signalling, acts as a regulator of the proliferation and differentiation of hDPSCs. Our results suggest potential therapeutic avenues for dentin formation and regenerative endodontics in patients with dentin dysplasia type I.
我们之前的研究表明，液泡分选蛋白 4B（VPS4B）的显性突变，一种 AAA ATPase 家族的成员，会导致牙本质发育不全 I 型。本研究旨在探讨 VPS4B 在人牙髓干细胞（hDPSCs）中的作用，并阐明其潜在的分子机制。在这项研究中，我们发现 VPS4B 在小鼠磨牙牙胚的牙髓细胞中高度表达，并且在 hDPSCs 的成牙本质分化过程中，VPS4B 的表达显著增加。下调 VPS4B 抑制 hDPSCs 的增殖、迁移和成牙本质分化。此外，用 Wnt-β-catenin 信号通路的激动剂氯化锂处理，部分逆转了 VPS4B 敲低对 hDPSCs 增殖和成牙本质分化的抑制作用。总之，我们的研究结果表明，VPS4B 通过 Wnt-β-catenin 信号通路，作为 hDPSCs 增殖和分化的调节剂。我们的研究结果为牙本质发育不全 I 型患者的牙本质形成和再生性牙髓治疗提供了潜在的治疗途径。
