N-acetylcysteine protects dental pulp stromal cells from HEMA-induced apoptosis by inducing differentiation of the cells
N-acetylcysteine protects dental pulp stromal cells from HEMA-induced apoptosis by inducing differentiation of the cells
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DOI：
10.1016/j.freeradbiomed.2007.07.011
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发表时间：
2007-11-15
影响因子：
7.4
通讯作者：
Jewett, Anahid
中科院分区：
文献类型：
--
作者：
Paranjpe, Avina;Cacalano, Nicholas A.;Jewett, Anahid
树脂基材料目前广泛用于牙科修复。虽然使用这些材料对患者具有美学吸引力，但它具有局部和全身不良反应的风险。潜在的风险是对细胞的直接损伤和诱导基于免疫的超敏反应。牙髓基质细胞（DPSC）和口腔角质形成细胞是在牙科漂白后可能与牙科树脂如甲基丙烯酸2-羟乙酯（HEMA）接触的主要细胞类型。在这里，我们表明，N-乙酰半胱氨酸（NAC）抑制HEMA诱导的凋亡细胞死亡，并恢复DPSC和口腔上皮细胞的功能。NAC通过诱导DPSC的分化来抑制HEMA介导的毒性，因为分化期间诱导的牙本质唾液蛋白、骨桥蛋白（OPN）、骨钙蛋白和碱性磷酸酶的基因也被NAC诱导。与NAC不同，维生素E和C是已知的抗氧化剂化合物，未能防止HEMA介导的细胞死亡或人DPSC的VEGF分泌减少。更重要的是，当单独或与HEMA组合添加时，维生素E和维生素C不会增加OPN的基因表达，此外维生素E抑制NAC对DPSC的保护作用。NAC抑制了HEMA介导的NF-κ B活性降低，从而为细胞提供了存活机制。总之，本文报道的研究表明，未分化的DPSC对HEMA诱导的细胞死亡具有极高的敏感性，它们对NAC的反应性分化导致NF-κ B活性增加，这可能为它们增加对HEMA介导的功能丧失和细胞死亡的保护提供了基础。(C)2007年爱思唯尔公司All rights reserved.
Resin-based materials are now widely used in dental restorations. Although the use of these materials is aesthetically appealing to patients, it carries the risk of local and systemic adverse effects. The potential risks are direct damage to the cells and induction of immune-based hypersensitivity reactions. Dental pulp stromal cells (DPSCs) and oral keratinocytes are the major cell types which may come in contact with dental resins such as 2-hydroxyethyl methacrylate (HEMA) after dental restorations. Here we show that N-acetylcysteine (NAC) inhibits HEMA-induced apoptotic cell death and restores the function of DPSCs and oral epithelial cells. NAC inhibits HEMA-mediated toxicity through induction of differentiation in DPSCs, because the genes for dentin sialoprotein, osteopontin (OPN), osteocalcin, and alkaline phosphatase, which are induced during differentiation, are also induced by NAC. Unlike NAC, vitamins E and C, which are known antioxidant compounds, failed to prevent either HEMA-mediated cell death or the decrease in VEGF secretion by human DPSCs. More importantly, when added either alone or in combination with HEMA, vitamin E and vitamin C did not increase the gene expression for OPN, and in addition vitamin E inhibited the protective effect of NAC on DPSCs. NAC inhibited the HEMA-mediated decrease in NF-kappa B activity, thus providing a survival mechanism for the cells. Overall, the studies reported in this paper indicate that undifferentiated DPSCs have exquisite sensitivity to HEMA-induced cell death, and their differentiation in response to NAC resulted in an increased NF-kappa B activity, which might have provided the basis for their increased protection from HEMA-mediated functional loss and cell death. (C) 2007 Elsevier Inc. All rights reserved.