Lithium-containing surface pre-reacted glass fillers enhance hDPSC functions and induce reparative dentin formation in a rat pulp capping model through activation of Wnt/β-catenin signaling
Lithium-containing surface pre-reacted glass fillers enhance hDPSC functions and induce reparative dentin formation in a rat pulp capping model through activation of Wnt/β-catenin signaling
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DOI：
10.1016/j.actbio.2019.06.016
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发表时间：
2019-09-15
影响因子：
9.7
通讯作者：
Hayashi, Mikako
中科院分区：
文献类型：
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作者：
Ali, Manahil;Okamoto, Motoki;Hayashi, Mikako
表面预反应玻璃（S-PRG）填料是一种新型的生物活性分子，用于牙科临床工作中填充牙齿缺损。这些填充物释放各种类型的离子（Al-+（3）、BO-3、Na+、SiO 3 -2、Sr+2和F-），并表现出高生物相容性、抗菌能力、减少的斑块积累和增强的成骨细胞分化。我们以前的研究表明，S-PRG填充剂的水泥可以诱导大鼠模型中三级牙本质的形成。先前的工作也表明锂离子可以在体外激活Wnt/β-catenin信号通路，并在体内诱导活髓切断牙齿的牙本质形成。在目前的研究中，我们试图通过掺入LiCl来增强S-PRG水泥的效果。我们发现，从S-PRG/氯化锂组合水泥洗脱液的人牙髓干细胞的治疗导致细胞迁移，分化和矿化在体外上调。在盖髓动物实验中，我们发现S-PRG/LiCl水门汀可以在盖髓后28天诱导三级牙本质形成。在加帽后7天，我们使用免疫荧光鉴定了β-连环蛋白和Axin 2表达，这指示了Wnt/β-连环蛋白信号传导活性。总之，S-PRG/LiCl水泥是非常有效的促进人类牙髓干细胞的配置文件，并通过激活Wnt/β-catenin经典信号通路在大鼠牙齿中增强修复性牙本质的形成。我们发现，这种新的组合水泥通过激活牙髓中的内源性Wnt/β-连环蛋白信号通路促进积极的细胞反应。Wnt/β-连环蛋白经典信号通路参与许多发育和创伤愈合过程。系统检测了S-PRG水泥中锂离子的释放量
Surface pre-reacted glass (S-PRG) fillers are new bioactive molecules used in dental clinic work to fill tooth defects. These fillers release various types of ions (Al-+(3), BO-3, Na+, SiO3-2, Sr+2 and F-) and exhibit high biocompatibility, antibacterial capability, reduced plaque accumulation, and enhanced osteoblast differentiation. We previously showed that cement of S-PRG fillers could induce tertiary dentin formation in rat models. Previous work also showed that lithium ions can activate the Wnt/beta-catenin signaling pathway in vitro and induce dentin formation in pulpotomized teeth in vivo. In the current study, we sought to enhance the effect of S-PRG cement by incorporating LiCl. We show that treatment of human dental pulp stem cells with eluates from S-PRG/LiCl combination cements leads to an upregulation in cell migration, differentiation, and mineralization in vitro. In pulp-capping animal trials, we found that S-PRG/LiCl cements could induce tertiary dentin formation 28-days post-capping. At 7 days post-capping, we identified both beta-catenin and Axin2 expression using immunofluorescence, indicative of Wnt/beta-catenin signaling activity. In conclusion, S-PRG/LiCl cement is highly effective in promoting human dental pulp stem cells profiles and in enhancing reparative dentin formation in rat teeth through activation of the Wnt/beta-catenin canonical signaling pathway.Statement of SignificanceThis is the first study to assess the behavior of S-PRG fillers containing lithium ions on human dental pulp stem cells. We show that this new combination cement promotes positive cell responses by activating the endogenous Wnt/beta-catenin signaling pathway in the pulp. The Wnt/beta-catenin canonical signaling pathway is involved in many developmental and wound healing processes. The released lithium ions from the S-PRG cement were systematically detected