Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA.
Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA.
Int J Mol Sci. 2023 Jul 28;24(15):12105. doi: 10.3390/ijms241512105.
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 -induced miRNAs, this study was designed to delineate the global miRNA expression kinetics during progression of periodontitis in mice infected with by using NanoString nCounter miRNA panels. All of the -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 ( < 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 -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 infection; the combination of three specific miRNAs, miR-486, miR-126-3p, and miR-126-5p, may serve as an invasive biomarker of in PD. These miRNAs may have a significant role in PD pathogenesis, and this research establishes a link between miRNA, periodontitis, and systemic diseases.
miRNAs 是真核生物基因表达和宿主免疫的主要调节剂，在牙周病（PD）发病机制中的炎症介导途径中发挥重要作用。在使用部分人类口腔微生物进行的全球 miRNA 分析中扩展了我们之前的观察结果，并且缺乏涉及口腔螺旋体诱导的 miRNA 的体内研究，本研究旨在使用 NanoString nCounter miRNA 面板描绘感染小鼠牙周炎进展过程中的全局 miRNA 表达动力学。所有感染的雄性和雌性小鼠在 8 周和 16 周时在牙龈表面均显示出细菌定植（100％），并且牙槽骨吸收增加（<0.0001）。确定了总共 70 个差异表达/调节（DE）至少 1.0 倍的 miRNA（26 个上调和 44 个下调）。nCounter miRNA 表达谱分析鉴定了 13 个上调的 miRNA（例如，miR-133a，miR-378）和 25 个下调的 miRNA（例如，miR-375，miR-34b-5p）在感染期间的感染小鼠下颌骨中，而在感染 8 周时观察到 13 个上调的 miRNA（例如，miR-486，miR-126-5p）和 19 个下调的 miRNA（miR-2135，miR-142-3p）在感染 16 周时观察到。一个 miRNA（miR-126-5p）在感染 8 周和 16 周之间表现出显著差异。有趣的是，miR-126-5p 已被证明是牙周炎和冠心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 在牙周炎和糖尿病患者的牙龈斑块和唾液样本中均有报道。京都基因与基因组百科全书（KEGG）分析显示 DE miRNA 的各种功能途径，例如细菌入侵上皮细胞，Ras 信号传导，FcγR 介导的吞噬作用，破骨细胞分化，黏着信号传导和泛素介导的蛋白水解。这是首次在不同时间点感染小鼠下颌骨中研究 DE miRNAs；三种特定 miRNA（miR-486、miR-126-3p 和 miR-126-5p）的组合可能作为 PD 中 的侵袭性生物标志物。这些 miRNA 在 PD 发病机制中可能具有重要作用，该研究建立了 miRNA，牙周炎和系统性疾病之间的联系。
