Activation of NF-kappa B-Autophagy Axis by 2-Hydroxyethyl Methacrylate Commits Dental Mesenchymal Cells to Apoptosis
Activation of NF-kappa B-Autophagy Axis by 2-Hydroxyethyl Methacrylate Commits Dental Mesenchymal Cells to Apoptosis
复制标题
甲基丙烯酸 2-羟乙酯激活 NF-kappa B-自噬轴使牙科间充质细胞凋亡
DOI：
10.1093/toxsci/kfx023
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发表时间：
2017
影响因子：
3.8
通讯作者：
Peng Bin
中科院分区：
文献类型：
--
作者：
Yu Jing-jing;Zhu Ling-xin;Zhang Jie;Liu Shan;Lv Feng-yuan;Cheng Xue;Liu Guo-jing;Peng Bin
2-甲基丙烯酸羟乙酯（HEMA）是在牙科治疗期间从不完全聚合的牙科修复和粘合生物材料释放的主要树脂单体。自噬和凋亡在生物学上有着密切的联系，在各种情况下，它们之间的关系是复杂的。本研究旨在探讨自噬在HEMA诱导的牙间充质细胞凋亡中的作用。我们将DMC暴露于不同浓度的HEMA。当暴露于HEMA时，细胞活力显示出时间和浓度依赖性降低。我们发现，HEMA暴露增加了自噬空泡和自噬生物标志物（Beclin 1，Atg 5和LC 3）的表达。与自噬抑制剂（3-甲基腺嘌呤和氯喹）预孵育显著防止了HEMA诱导的细胞凋亡。有趣的是，HEMA启动核因子-κB（NF-κB）表达和核转位，而NF-κB抑制剂（Bay 11-7082）显著抑制HEMA诱导的自噬激活和凋亡。与体外结果一致，在离体牙切片器官培养模型中，HEMA处理导致牙髓组织毒性和典型自噬空泡的活化。综上所述，我们证明了NF-κB信号通路在HEMA诱导的DMCs自噬的上游发挥作用，NF-κ B-自噬轴的激活是HEMA诱导DMCs凋亡的原因。我们的研究结果为牙科治疗过程中树脂单体介导的牙髓损伤机制提供了新的见解，强调NF-κ B-自噬轴的激活是HEMA介导的细胞凋亡的重要机制。
2-hydroxyethyl methacrylate (HEMA) is the major resin monomer that is released from incomplete polymerized dental restorative and adhesive biomaterials during dental therapy. Autophagy and apoptosis are biologically connected and the relationship between autophagy and apoptosis is complex under various circumstances. This study aimed to determine whether autophagy is activated by HEMA and further explore the function of autophagy during the HEMA-induced apoptosis of dental mesenchymal cells (DMCs). We exposed DMCs to different concentrations of HEMA. Cell viability showed a time- and concentration-dependent decrease when exposed to HEMA. We showed that HEMA exposure increased autophagic vacuoles and the expression of autophagic biomarkers (Beclin1, Atg5 and LC3). Pre-incubated with autophagy inhibitors (3-methyladenine and chloroquine) significantly prevented HEMA-induced apoptosis. Interestingly, HEMA initiated nuclear factor-κB (NF-κB) expression and nuclear translocation, whereas the NF-κB inhibitor (Bay 11-7082) markedly suppressed HEMA-induced autophagic activation and apoptosis. As is consistent with the in vitro results, HEMA treatment resulted in dental pulp tissue toxicity and activation of typical autophagic vacuoles in the tooth slice organ culture model ex vivo. In summary, we demonstrated that NF-κB signaling functioned upstream of HEMA-inducecd autophagy in DMCs and that the activation of NF-κB-autophagy axis was responsible for HEMA-induced apoptosis. Our findings provide novel insights into the mechanisms of resin monomer-mediated dental pulp damage during dental treatment, highlighting the activation of NF-κB-autophagy axis as an important mechanism of HEMA-mediated apoptosis.