Clinic of Conservative and Preventive Dentistry, Center of Dental Medicine, University of Zurich, Zurich, Switzerland.
Laboratory of Applied Periodontal and Peri-implantitis Sciences, Clinic of Conservative and Preventive Dentistry, Center of Dental Medicine, University of Zurich, Zurich, Switzerland.
PLoS One. 2019 Jul 3;14(7):e0219181. doi: 10.1371/journal.pone.0219181. eCollection 2019.
Periodontal ligament stem cells (PDLSC) play an important role in periodontal tissue homeostasis/turnover and could be applied in cell-based periodontal regenerative therapy. Bacterial supernatants secreted from diverse periodontal bacteria induce the production of cytokines that contribute to local periodontal tissue destruction. However, little is known about the impact of whole bacterial toxins on the biological behavior of PDLSC. Therefore this study investigated whether proliferation, migration, inflammatory cytokines expression and transcriptional profile would be affected by exposure to endotoxins from bacterial species found in the subgingival plaque. PDLSC were cultured with the following bacterial supernatants: S. mutans, S. anginosus, P. intermedia, F. nucleatum, P. gingivalis and T. denticola. These supernatants were prepared in dilutions of 1:1000, 1:500, 1:300 and 1:50. Using quantitative RT-PCR, gene expression of selected inflammatory cytokines (IL-6, IL-8 and IL-1β) and cell-surface receptors (TLR2, TLR4) showed upregulation of ≈2.0- to 3.0-fold, when exposed to P. intermedia, F. nucleatum, P. gingivalis and T. denticola. However, supernatants did not affect proliferation (MTT) and migration (wound scratch assays) of PDLSC. Next generation RNA sequencing confirmed modified lineage commitment of PDLSC by stimulating chondrogenesis, adipogenesis and inhibition of osteogenesis under P. gingivalis supernatant treatment compared to control. Taken together, this study shows stem cell immunomodulatory response to different periodontal bacteria supernatant and suggests that stem cell transcriptional capacity, migration/proliferation and osteogenesis may differ in the presence of those pathogens. These results bring into question stem cell contribution to periodontal tissue regeneration and onset of inflammation.
牙周膜干细胞（PDLSC）在牙周组织稳态/更新中发挥重要作用，可应用于基于细胞的牙周再生治疗。不同牙周细菌分泌的细菌上清液会诱导细胞因子的产生，从而导致局部牙周组织破坏。然而，人们对全细菌毒素对 PDLSC 生物学行为的影响知之甚少。因此，本研究探讨了暴露于龈下菌斑中发现的细菌的内毒素是否会影响 PDLSC 的增殖、迁移、炎症细胞因子表达和转录谱。将 PDLSC 与以下细菌上清液一起培养：变形链球菌、中间普氏菌、伴放线放线杆菌、具核梭杆菌、牙龈卟啉单胞菌和牙髓卟啉单胞菌。这些上清液以 1:1000、1:500、1:300 和 1:50 的稀释度制备。通过定量 RT-PCR，选择的炎症细胞因子（IL-6、IL-8 和 IL-1β）和细胞表面受体（TLR2、TLR4）的基因表达显示，当暴露于中间普氏菌、具核梭杆菌、牙龈卟啉单胞菌和牙髓卟啉单胞菌时，表达上调约 2.0-3.0 倍。然而，上清液并未影响 PDLSC 的增殖（MTT）和迁移（划痕实验）。下一代 RNA 测序证实，与对照相比，牙龈卟啉单胞菌上清液处理可使 PDLSC 向软骨形成、脂肪形成和抑制成骨方向分化，从而改变其谱系决定。总之，本研究表明，不同牙周细菌上清液对干细胞具有免疫调节作用，并提示在存在这些病原体的情况下，干细胞的转录能力、迁移/增殖和成骨作用可能存在差异。这些结果质疑了干细胞对牙周组织再生和炎症发生的贡献。
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