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二缩三乙二醇二甲基丙烯酸酯(TEGDMA)诱导牙髓细胞中半胱天冬酶依赖性和非依赖性凋亡途径。

TEGDMA (Triethylene Glycol Dimethacrylate) Induces Both Caspase-Dependent and Caspase-Independent Apoptotic Pathways in Pulp Cells.

作者信息

Lovász Bálint Viktor, Berta Gergely, Lempel Edina, Sétáló György, Vecsernyés Mónika, Szalma József

机构信息

Department of Oral and Maxillofacial Surgery, University of Pécs, Medical School, 5. Dischka St., 7621 Pécs, Hungary.

Department of Medical Biology and Central Electron Microscope Laboratory, University of Pécs Medical School, 12. Szigeti St., 7624 Pécs, Hungary.

出版信息

Polymers (Basel). 2021 Feb 25;13(5):699. doi: 10.3390/polym13050699.

Abstract

Monomers leached from resin-based composites (RBCs) may reach intrapulpal concentrations of the millimolar (mM) range, which could contribute to inflammation. The aim of this investigation was to assess the cytotoxicity of triethylene glycol dimethacrylate (TEGDMA) monomers on pulp cells as well as to identify molecular mechanisms leading to apoptosis. Pulp cells were harvested from molars extracted for orthodontic reasons and cultured through an explant method. To assess cytotoxicity, cells underwent a 5-day exposure to 0.75, 1.5, and 3 mM TEGDMA and were subject to cell counting and WST-1 staining. Based on the findings, cells were subsequently exposed to 0.1, 0.2, 0.75, 1.5, and 3 mM TEGDMA for 24 h to uncover the details of apoptosis. Changes in the production or cleavage of the apoptosis-specific proteins caspase-8, caspase-9, caspase-3, caspase-12, and Apoptosis-Inducing Factor (AIF) were measured by Western blot. The 5-day study showed concentration- and time-dependent cytotoxicity. Significant cell death was detected after 24 h with TEGDMA concentrations of 1.5 and 3 mM. One-day exposure to TEGDMA led to the activation of caspase-8, -9, -3, and -12 and an increased AIF production. Results suggest that relevant concentrations of TEGDMA monomers, leached from RBCs, induce apoptosis in pulp cells through both caspase-dependent as well as caspase-independent mechanisms. Endoplasmic reticulum stress and the activation of caspase-independent apoptotic pathways may be further mechanisms by which monomers induce apoptosis in pulp cells.

摘要

从树脂基复合材料(RBCs)中渗出的单体可能会在牙髓内达到毫摩尔(mM)级别的浓度,这可能会引发炎症。本研究的目的是评估二缩三乙二醇二甲基丙烯酸酯(TEGDMA)单体对牙髓细胞的细胞毒性,并确定导致细胞凋亡的分子机制。从因正畸原因拔除的磨牙中采集牙髓细胞,并通过外植体法进行培养。为了评估细胞毒性,将细胞暴露于0.75、1.5和3 mM的TEGDMA中5天,并进行细胞计数和WST-1染色。基于这些发现,随后将细胞暴露于0.1、0.2、0.75、1.5和3 mM的TEGDMA中24小时,以揭示细胞凋亡的细节。通过蛋白质印迹法检测凋亡特异性蛋白半胱天冬酶-8、半胱天冬酶-9、半胱天冬酶-3、半胱天冬酶-12和凋亡诱导因子(AIF)的产生或裂解变化。为期5天的研究显示出浓度和时间依赖性的细胞毒性。在24小时后,检测到TEGDMA浓度为1.5和3 mM时出现显著的细胞死亡。暴露于TEGDMA一天导致半胱天冬酶-8、-9、-3和-12的激活以及AIF产生增加。结果表明,从RBCs中渗出的相关浓度的TEGDMA单体通过半胱天冬酶依赖性和非依赖性机制诱导牙髓细胞凋亡。内质网应激和非半胱天冬酶依赖性凋亡途径的激活可能是单体诱导牙髓细胞凋亡的进一步机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330d/7956203/cb5cdd5d445f/polymers-13-00699-g001.jpg

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