N-acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging.
N-acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging.
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DOI：
10.1186/s13287-022-03161-y
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发表时间：
2022-09-08
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
--
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牙囊干细胞（DFSC）具有间充质干细胞特性，具有牙槽骨再生的潜力。干细胞的特性会受到活性氧（ROS）的损害，这促使我们研究清除ROS对基于干细胞的组织再生的重要性。本研究旨在探讨N-乙酰半胱氨酸（NAC）作为一种新型抗氧化剂，对DFSC及其基牙槽骨再生的影响及其机制。在补充有不同浓度的NAC（0-10 mM）的培养基中培养DFSC。在人DFSC（hDFSC）中进行体外细胞学实验、RNA测序和抗氧化剂测定。建立大鼠上颌第一磨牙拔除模型，术后第7天行组织学和放射学检查，观察NAC、大鼠DFSCs（rDFSCs）和NAC处理的rDFSCs局部移植后拔牙窝牙槽骨再生情况。5 mM NAC处理的hDFSC表现出更好的增殖、更少的衰老率、更高的干细胞特异性标志物和免疫相关因子表达以及最强的成骨分化;其他浓度也有利于维持干细胞特性。RNA测序鉴定了具有和不具有5 mM NAC的hDFSC之间的803个差异表达基因。生物信息学分析结果显示，394个基因的功能和途径分别为骨化和PI 3 K/AKT途径。NAC处理后，细胞内活性氧（ROS）、超氧化物（O2）、过氧化氢（H2 O2）水平降低，抗氧化剂（谷胱甘肽、过氧化氢酶、超氧化物歧化酶）水平升高，PI 3 K/AKT信号通路（PI 3 K-p110、PI 3 K-p85、AKT、phosphorylated-PI 3 K-p85、phosphorylated-AKT）上调，活性氧（ROS）水平在PI 3 K/AKT抑制后反弹。局部移植NAC、rDFSCs及NAC处理的rDFSCs均能促进拔牙后牙槽骨的形成，其中NAC处理的rDFSCs效果最好。适当浓度的NAC通过PI 3 K/AKT/ROS信号通路增强DFSC的特性，特别是成骨，并为基于干细胞的牙槽骨再生提供临床潜力。在线版本包含补充材料，可通过10.1186/s13287-022-03161-y获得。
Dental follicle stem cells (DFSCs) show mesenchymal stem cell properties with the potential for alveolar bone regeneration. Stem cell properties can be impaired by reactive oxygen species (ROS), prompting us to examine the importance of scavenging ROS for stem cell-based tissue regeneration. This study aimed to investigate the effect and mechanism of N-acetylcysteine (NAC), a promising antioxidant, on the properties of DFSCs and DFSC-based alveolar bone regeneration. DFSCs were cultured in media supplemented with different concentrations of NAC (0–10 mM). Cytologic experiments, RNA-sequencing and antioxidant assays were performed in vitro in human DFSCs (hDFSCs). Rat maxillary first molar extraction models were constructed, histological and radiological examinations were performed at day 7 post-surgery to investigate alveolar bone regeneration in tooth extraction sockets after local transplantation of NAC, rat DFSCs (rDFSCs) or NAC-treated rDFSCs. 5 mM NAC-treated hDFSCs exhibited better proliferation, less senescent rate, higher stem cell-specific marker and immune-related factor expression with the strongest osteogenic differentiation; other concentrations were also beneficial for maintaining stem cell properties. RNA-sequencing identified 803 differentially expressed genes between hDFSCs with and without 5 mM NAC. “Developmental process (GO:0032502)” was prominent, bioinformatic analysis of 394 involved genes revealed functional and pathway enrichment of ossification and PI3K/AKT pathway, respectively. Furthermore, after NAC treatment, the reduction of ROS levels (ROS, superoxide, hydrogen peroxide), the induction of antioxidant levels (glutathione, catalase, superoxide dismutase), the upregulation of PI3K/AKT signaling (PI3K-p110, PI3K-p85, AKT, phosphorylated-PI3K-p85, phosphorylated-AKT) and the rebound of ROS level upon PI3K/AKT inhibition were showed. Local transplantation of NAC, rDFSCs or NAC-treated rDFSCs was safe and promoted oral socket bone formation after tooth extraction, with application of NAC-treated rDFSCs possessing the best effect. The proper concentration of NAC enhances DFSC properties, especially osteogenesis, via PI3K/AKT/ROS signaling, and offers clinical potential for stem cell-based alveolar bone regeneration. The online version contains supplementary material available at 10.1186/s13287-022-03161-y.
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影响因子：
64.8
作者：
Nakada, Yuji;Canseco, Diana C.;Sadek, Hesham A.
通讯作者：
Sadek, Hesham A.
影响因子：
3
作者：
Lima, Rodrigo Lopes;Holanda-Afonso, Rosenilde Carvalho;Souza, Margareth Maria
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
Pei Y;Liu H;Yang Y;Yang Y;Jiao Y;Tay FR;Chen J
通讯作者：
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影响因子：
4.6
作者：
Kornienko, Ju. S.;Smirnova, I. S.;Lyublinskaya, O. G.
通讯作者：
Lyublinskaya, O. G.