Division of Oral Biological Sciences, Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka, Japan.
Division of Oral Health, Growth and Development, Department of Pediatric Dentistry, Kyushu University Graduate School of Dental Science, Fukuoka, Japan.
J Endod. 2019 May;45(5):591-598.e6. doi: 10.1016/j.joen.2019.01.016. Epub 2019 Apr 3.
Stem cells isolated from the root apical papilla of human teeth (stem cells from the apical papilla [SCAPs]) are capable of forming tooth root dentin and are a feasible source for bioengineered tooth root regeneration. In this study, we examined the effect of acetylsalicylic acid (ASA) on odontogenic differentiation of SCAPs in vitro and in vivo.
SCAPs were cultured under odontogenic conditions supplemented with or without ASA. ASA-treated SCAPs were also subcutaneously transplanted into immunocompromised mice.
ASA accelerates in vitro and in vivo odontogenic differentiation of SCAPs associated with down-regulation of runt-related nuclear factor 2 and up-regulation of specificity protein 7, nuclear factor I C, and dentin phosphoprotein. ASA up-regulated the phosphorylation of AKT in the odontogenic SCAPs. Of interest, pretreatments with phosphoinositide 3-kinase inhibitor LY294402 and small interfering RNA for AKT promoted ASA-induced in vitro and in vivo odontogenic differentiation of SCAPs. LY294402 and small interfering RNA for AKT also suppressed the ASA-induced expression of runt-related nuclear factor 2 and enhanced ASA-induced expression of specificity protein 7, nuclear factor I C, and dentin phosphoprotein in SCAPs.
These findings suggest that a combination of ASA treatment and suppressive regulation of the phosphoinositide 3-kinase-AKT signaling pathway is a novel approach for SCAP-based tooth root regeneration.
从人牙齿根尖乳头分离的干细胞（根尖乳头干细胞[SCAPs]）能够形成牙本质，并为生物工程牙根再生提供了可行的来源。本研究检测了乙酰水杨酸（ASA）对 SCAPs 体外和体内成牙分化的影响。
在成牙条件下培养 SCAPs，同时添加或不添加 ASA。将 ASA 处理的 SCAPs 也皮下移植到免疫缺陷小鼠中。
ASA 加速了 SCAPs 的体外和体内成牙分化，与 runt 相关核因子 2 的下调和特异性蛋白 7、核因子 I C 和牙本质磷蛋白的上调有关。ASA 上调了成牙 SCAPs 中 AKT 的磷酸化。有趣的是，PI3K 抑制剂 LY294402 和 AKT 的小干扰 RNA 的预处理促进了 ASA 诱导的 SCAPs 的体外和体内成牙分化。LY294402 和 AKT 的小干扰 RNA 也抑制了 ASA 诱导的 runt 相关核因子 2 的表达，并增强了 ASA 诱导的 SCAPs 中特异性蛋白 7、核因子 I C 和牙本质磷蛋白的表达。
这些发现表明，ASA 治疗与抑制 PI3K-AKT 信号通路的结合是基于 SCAP 的牙根再生的一种新方法。
