Department of Human Microbiome, School and Hospital of Stomatology, Shandong University and Shandong Provincial Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.
Department of Periodontology, School of Stomatology, Shandong University, Jinan, China.
Front Cell Infect Microbiol. 2019 Dec 17;9:429. doi: 10.3389/fcimb.2019.00429. eCollection 2019.
is one of the most frequent pathogenic bacteria causing periodontitis. The direct effect of () on oral stem cells has rarely been reported. In this study, we aimed to evaluate how gingiva-derived mesenchymal stem cells (GMSCs) respond to a direct challenge with . GMSCs were isolated by the limiting dilution method and exposed to at various multiplicities of infection (MOIs; :cell ratios of 10:1, 50:1, and 100:1) for 24 h to 4 weeks. Our results indicated that significantly inhibited cell proliferation in a dose-dependent manner and promoted cell migration and the release of chemokines/cytokines, such as CCL2, CXCL1, and IL-6. Additionally, inhibited GMSC osteogenic differentiation partly by decreasing alkaline phosphatase (ALP) activity, mineralized nodule formation, and osteogenesis-related gene and protein expression. RNA-sequencing analyses indicated that time-dependently activated cellular signaling pathways during the process of osteogenic differentiation. A total of 64 cell differentiation-related genes were found to be differentially expressed between non-infected and -infected GMSCs at 3, 7, 14, and 21 d. Intriguingly, we discovered that the 64 cell differentiation-related differentially expressed genes (DEGs) were significantly enriched in cancer-related pathways, such as bone cancer, osteosarcoma and bone marrow cancer, which provides new insight into tumorigenesis during the process of GMSC osteogenic differentiation. In conclusion, this study demonstrates that persistent exposure to promotes cell migration and chemokine/cytokine release and inhibits the proliferation and osteogenic differentiation of GMSCs. Our study provides a novel and long-time bacteria-cell co-culture model and makes a foundation for the future mechanistic studies of GMSCs under infection.
是导致牙周炎最常见的致病菌之一。关于（）对口腔干细胞的直接作用鲜有报道。在本研究中，我们旨在评估牙龈来源间充质干细胞（GMSCs）如何应对（）的直接挑战。通过有限稀释法分离 GMSCs，并用不同感染复数（MOI；细胞比为 10:1、50:1 和 100:1）的（）处理 GMSCs 24 h 至 4 周。结果表明，（）呈剂量依赖性显著抑制细胞增殖，并促进细胞迁移和趋化因子/细胞因子的释放，如 CCL2、CXCL1 和 IL-6。此外，（）通过降低碱性磷酸酶（ALP）活性、矿化结节形成和骨形成相关基因和蛋白表达，部分抑制 GMSC 成骨分化。RNA 测序分析表明，（）在成骨分化过程中时间依赖性激活细胞信号通路。在非感染和感染 GMSC 之间，在 3、7、14 和 21 天，总共发现 64 个与细胞分化相关的基因存在差异表达。有趣的是，我们发现 64 个与细胞分化相关的差异表达基因（DEGs）在与癌症相关的途径中显著富集，如骨癌、骨肉瘤和骨髓癌，这为 GMSC 成骨分化过程中的肿瘤发生提供了新的见解。总之，本研究表明持续暴露于（）可促进细胞迁移和趋化因子/细胞因子释放，并抑制 GMSCs 的增殖和成骨分化。本研究提供了一种新的、长时间的细菌-细胞共培养模型，为今后（）感染下 GMSC 的机制研究奠定了基础。
