Dental and Advanced Studies Research Center (CIEAO), Faculty of Dentistry, Autonomous University State of Mexico, Toluca, Mexico; Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.
Institute for Advanced Bioscience, Keio University, Tsuruoka, Yamagata, Japan.
Biomaterials. 2015 Jul;57:33-40. doi: 10.1016/j.biomaterials.2015.03.059. Epub 2015 Apr 22.
Although nanoparticles (NPs) has afforded considerable benefits in various fields of sciences, several reports have shown their harmful effects, suggesting the necessity of adequate risk assessment. To clarify the mechanism of titanium dioxide nanoparticles (TiO2 NPs)-enhanced gingival inflammation, we conducted the full-scale metabolomic analyses of human gingival fibroblast cells treated with IL-1β alone or in combination with TiO2 NPs. Observation with transmission electron microscope demonstrated the incorporation of TiO2 NPs into vacuoles of the cells. TiO2 NPs significantly enhanced the IL-1β-induced prostaglandin E2 production and COX-1 and COX-2 protein expression. IL-1β reduced the intracellular concentrations of overall primary metabolites especially those of amino acid, urea cycle, polyamine, S-adenosylmethione and glutathione synthetic pathways. The addition of TiO2 NPs further augmented these IL-1β-induced metabolic changes, recommending careful use of dental materials containing TiO2 NPs towards patients with gingivitis or periodontitis. The impact of the present study is to identify the molecular targets of TiO2 NPs for the future establishment of new metabolic markers and therapeutic strategy of gingival inflammation.
尽管纳米颗粒（NPs）在科学的各个领域都带来了相当大的好处，但有几项报告显示了它们的有害影响，这表明有必要进行充分的风险评估。为了阐明二氧化钛纳米颗粒（TiO2 NPs）增强牙龈炎症的机制，我们对单独用 IL-1β 或与 TiO2 NPs 联合处理的人牙龈成纤维细胞进行了全面的代谢组学分析。透射电子显微镜观察显示 TiO2 NPs 被纳入细胞的空泡中。TiO2 NPs 显著增强了 IL-1β 诱导的前列腺素 E2 产生以及 COX-1 和 COX-2 蛋白表达。IL-1β 降低了细胞内的总体初级代谢物浓度，特别是氨基酸、尿素循环、多胺、S-腺苷甲硫氨酸和谷胱甘肽合成途径的代谢物浓度。TiO2 NPs 的加入进一步加剧了这些由 IL-1β 诱导的代谢变化，这提醒我们在治疗患有牙龈炎或牙周炎的患者时要谨慎使用含有 TiO2 NPs 的牙科材料。本研究的意义在于确定 TiO2 NPs 的分子靶标，以便为未来建立新的代谢标志物和治疗牙龈炎症的策略提供依据。
