Department of Dental Biomaterials Science and Dental Research Institute, School of Dentistry, Seoul National University, Chongro-ku, Seoul 110-749, Korea.
J Biomed Mater Res B Appl Biomater. 2011 Aug;98(2):300-7. doi: 10.1002/jbm.b.31852. Epub 2011 May 20.
Triethyleneglycol dimethacrylate (TEGDMA) and 2-hydroxyethyl methacrylate (HEMA) are major resinous components of dental restorative materials and dentin bonding adhesives. Resin monomers are known to cause cytotoxicity in mammalian cells via oxidative stress and inhibit differentiation of dental pulp cells and osteoblasts. This study was aimed to investigate whether oxidative stress was involved in the inhibition of TEGDMA- and HEMA-induced differentiation. TEGDMA and HEMA reduced alkaline phosphatase (ALP) activity and the mRNA expression of the osteopontin (OPN) gene in MG63 cells at noncytotoxic concentrations. On the other hand, N-acetylcysteine (NAC) did not affect ALP activity at concentrations below 10 mM. Reduced ALP activity and OPN mRNA expression by TEGDMA were partially recovered via cotreatment with NAC. However, NAC did not exhibit significant effects in HEMA-treated cells. Glutathione (GSH) levels were also down-regulated by both TEGDMA and HEMA. The addition of NAC induced the partial recovery of GSH in cells treated with 0.5 mM TEGDMA. On the other hand, the levels of GSH in HEMA-treated cells were not affected by NAC. These results suggest that oxidative stress is involved in the suppression of differentiation by TEGDMA. Translocation of Nrf2 from the cytoplasm to the nucleus has been known to play a role in the suppression of osteogenic differentiation by oxidative stress. However, Nrf2 did not move into the nucleus in resin monomer-treated MG63 cells, suggesting the contribution of other signaling pathways to the suppressive effects of resin monomers.
三甘醇二甲基丙烯酸酯（TEGDMA）和 2-羟乙基甲基丙烯酸酯（HEMA）是牙科修复材料和牙本质粘结剂的主要树脂成分。已知树脂单体通过氧化应激导致哺乳动物细胞产生细胞毒性，并抑制牙髓细胞和成骨细胞的分化。本研究旨在探讨氧化应激是否参与了 TEGDMA 和 HEMA 诱导的分化抑制。在非细胞毒性浓度下，TEGDMA 和 HEMA 降低了 MG63 细胞中的碱性磷酸酶（ALP）活性和骨桥蛋白（OPN）基因的 mRNA 表达。另一方面，N-乙酰半胱氨酸（NAC）在低于 10mM 的浓度下不会影响 ALP 活性。通过与 NAC 共同处理，TEGDMA 降低的 ALP 活性和 OPN mRNA 表达部分得到恢复。然而，NAC 在 HEMA 处理的细胞中没有表现出显著的效果。TEGDMA 和 HEMA 还下调了谷胱甘肽（GSH）水平。添加 NAC 诱导了 0.5mM TEGDMA 处理的细胞中 GSH 的部分恢复。另一方面，NAC 对 HEMA 处理的细胞中的 GSH 水平没有影响。这些结果表明，氧化应激参与了 TEGDMA 诱导的分化抑制。核因子 E2 相关因子 2（Nrf2）从细胞质向细胞核的易位已被证明在氧化应激抑制成骨分化中起作用。然而，在树脂单体处理的 MG63 细胞中，Nrf2 没有进入细胞核，这表明其他信号通路对树脂单体的抑制作用有贡献。
