PDF(Pubmed)
Abstract：
miRNAs are major regulators of eukaryotic gene expression and host immunity, and play an important role in the inflammation-mediated pathways in periodontal disease (PD) pathogenesis. Expanding our previous observation with the global miRNA profiling using partial human mouth microbes, and lack of in vivo studies involving oral spirochete Treponema denticola-induced miRNAs, this study was designed to delineate the global miRNA expression kinetics during progression of periodontitis in mice infected with T. denticola by using NanoString nCounter® miRNA panels. All of the T. denticola-infected male and female mice at 8 and 16 weeks demonstrated bacterial colonization (100%) on the gingival surface, and an increase in alveolar bone resorption (p < 0.0001). A total of 70 miRNAs with at least 1.0-fold differential expression/regulation (DE) (26 upregulated and 44 downregulated) were identified. nCounter miRNA expression profiling identified 13 upregulated miRNAs (e.g., miR-133a, miR-378) and 25 downregulated miRNAs (e.g., miR-375, miR-34b-5p) in T. denticola-infected mouse mandibles during 8 weeks of infection, whereas 13 upregulated miRNAs (e.g., miR-486, miR-126-5p) and 19 downregulated miRNAs (miR-2135, miR-142-3p) were observed during 16 weeks of infection. One miRNA (miR-126-5p) showed significant difference between 8 and 16 weeks of infection. Interestingly, miR-126-5p has been presented as a potential biomarker in patients with periodontitis and coronary artery disease. Among the upregulated miRNAs, miR-486, miR-126-3p, miR-126-5p, miR-378a-3p, miR-22-3p, miR-151a-3p, miR-423-5p, and miR-221 were reported in human gingival plaques and saliva samples from periodontitis and with diabetes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed various functional pathways of DE miRNAs, such as bacterial invasion of epithelial cells, Ras signaling, Fc gamma R-mediated phagocytosis, osteoclast differentiation, adherens signaling, and ubiquitin mediated proteolysis. This is the first study of DE miRNAs in mouse mandibles at different time-points of T. denticola infection; the combination of three specific miRNAs, miR-486, miR-126-3p, and miR-126-5p, may serve as an invasive biomarker of T. denticola in PD. These miRNAs may have a significant role in PD pathogenesis, and this research establishes a link between miRNA, periodontitis, and systemic diseases.
摘要：
miRNA是真核生物基因表达和宿主免疫的主要调节因子,在牙周病(PD)的发病机制中,炎症介导的通路发挥着重要作用。通过使用部分人类口腔微生物的全局miRNA分析来扩展我们之前的观察结果，缺乏涉及口腔螺旋体诱导的miRNA的体内研究，本研究旨在通过使用NanoStringnCounter®miRNA面板来描述感染树突状念珠菌的小鼠牙周炎进展过程中的整体miRNA表达动力学。在第8周和第16周时，所有受T.denticola感染的雄性和雌性小鼠都在牙龈表面上显示出细菌定植（100％），牙槽骨吸收增加（p<0.0001）。鉴定了总共70种具有至少1.0倍差异表达/调节(DE)(26种上调和44种下调)的miRNA。nCountermiRNA表达谱分析鉴定出13种上调的miRNA(例如，miR-133a,miR-378)和25个下调的miRNA(例如，miR-375，miR-34b-5p）在感染后8周感染的小鼠下颌骨中，而13个上调的miRNA(例如，在16周的感染过程中观察到miR-486，miR-126-5p）和19个下调的miRNA（miR-2135，miR-142-3p）。一个miRNA(miR-126-5p)在感染8周和16周之间显示出显著差异。有趣的是,miR-126-5p已被提出作为牙周炎和冠状动脉疾病患者的潜在生物标志物。在上调的miRNA中，miR-486,miR-126-3p,miR-126-5p,miR-378a-3p,miR-22-3p,miR-151a-3p,miR-423-5p,和miR-221在牙周炎和糖尿病的人牙龈斑块和唾液样本中报告。京都基因和基因组百科全书（KEGG）分析揭示了DEmiRNA的各种功能途径，如细菌侵入上皮细胞，Ras信号,FcγR介导的吞噬作用，破骨细胞分化，信徒信号，和泛素介导的蛋白水解。这是首次研究小鼠下颌骨中不同时间点的DEmiRNAs；三种特定miRNAs的组合，miR-486,miR-126-3p,和miR-126-5p,可作为PD中的隐风直肠炎的侵袭性生物标志物。这些miRNAs可能在PD发病机制中具有重要作用，这项研究建立了miRNA之间的联系，牙周炎,和系统性疾病。
