Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA.
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Int J Mol Sci. 2022 May 4;23(9):5107. doi: 10.3390/ijms23095107.
Periodontitis (PD) is a polymicrobial dysbiotic immuno-inflammatory disease. It is more prevalent in males and has poorly understood pathogenic molecular mechanisms. Our primary objective was to characterize alterations in sex-specific microRNA (miRNA, miR) after periodontal bacterial infection. Using partial human mouth microbes (PAHMM) (Streptococcus gordonii, Fusobacterium nucleatum, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) in an ecological time-sequential polybacterial periodontal infection (ETSPPI) mouse model, we evaluated differential mandibular miRNA profiles by using high-throughput Nanostring nCounter® miRNA expression panels. All PAHMM mice showed bacterial colonization (100%) in the gingival surface, an increase in alveolar bone resorption (p < 0.0001), and the induction of a specific immunoglobin G antibody immune response (p < 0.001). Sex-specific differences in distal organ bacterial dissemination were observed in the heart (82% male vs. 28% female) and lungs (2% male vs. 68% female). Moreover, sex-specific differential expression (DE) of miRNA was identified in PAHMM mice. Out of 378 differentially expressed miRNAs, we identified seven miRNAs (miR-9, miR-148a, miR-669a, miR-199a-3p, miR-1274a, miR-377, and miR-690) in both sexes that may be implicated in the pathogenesis of periodontitis. A strong relationship was found between male-specific miR-377 upregulation and bacterial dissemination to the heart. This study demonstrates sex-specific differences in bacterial dissemination and in miRNA differential expression. A novel PAHMM mouse and ETSPPI model that replicates human pathobiology can be used to identify miRNA biomarkers in periodontitis.
牙周炎（PD）是一种多微生物失调性免疫炎症性疾病。它在男性中更为普遍，其发病的分子机制尚未被充分理解。我们的主要目标是描述牙周细菌感染后性别特异性微小 RNA（miRNA，miR）的变化。我们使用部分人类口腔微生物（PAHMM）（链球菌、核梭杆菌、牙龈卟啉单胞菌、齿密螺旋体和福赛斯坦纳菌）在生态时间顺序多细菌牙周感染（ETSPPI）小鼠模型中，通过高通量 Nanostring nCounter® miRNA 表达谱分析评估下颌 miRNA 图谱的差异。所有 PAHMM 小鼠的牙龈表面均显示出细菌定植（100%）、牙槽骨吸收增加（p<0.0001）和特异性免疫球蛋白 G 抗体免疫反应的诱导（p<0.001）。在心脏（82%男性与 28%女性）和肺部（2%男性与 68%女性）中观察到远端器官细菌播散存在性别差异。此外，在 PAHMM 小鼠中鉴定出了 miRNA 的性别特异性差异表达（DE）。在 378 个差异表达的 miRNA 中，我们在两种性别中都鉴定出了 7 个 miRNA（miR-9、miR-148a、miR-669a、miR-199a-3p、miR-1274a、miR-377 和 miR-690），它们可能与牙周炎的发病机制有关。发现 miR-377 在雄性中的上调与细菌向心脏的播散之间存在很强的相关性。本研究表明，在细菌播散和 miRNA 差异表达方面存在性别差异。该研究使用新型 PAHMM 小鼠和 ETSPPI 模型复制了人类的病理生理学，可用于鉴定牙周炎的 miRNA 生物标志物。
