To investigate whether oligomerization domains (NODs) are involved in Porphyromonas gingivalis-induced interleukin (IL)-6, IL-8, and vascular cell adhesion molecule (VCAM)-1 expression beyond Toll-like receptors (TLRs), we investigated the role of NOD1/2 in P. gingivalis-induced IL-6, IL-8, and VCAM-1 expression in human gingival fibroblasts (hGFs) and periodontal ligament cells (hPDLCs). The mechanism was explored by activation and silence of NODs, electrophoretic mobility shift assay (EMSA), and pathway blockade assays. Results showed that P. gingivalis could induce NOD1, NOD2, IL-6, IL-8, and VCAM-1 expression in hGFs and hPDLs at mRNA and protein levels. Activation of NOD1/2 by agonists could clearly upregulate the expression of these genes, while silence of NOD1/2 could remarkably attenuate them. EMSA and blockade of NF-κB and extracellular-signal-regulated kinase (ERK)1/2 pathway assays also verified that the two pathways were involved in NOD1/2-mediated IL-6, IL-8, and VCAM-1 expression. In conclusion, our findings demonstrated that P. gingivalis induced IL-6, IL-8, and VCAM-1 expression in hGFs and hPDLCs through NOD1/2-mediated NF-κB and ERK1/2 signaling pathways beyond TLRs.
The present results indicate that sICAM-1 levels are correlated to the severity of periodontitis. NOD1 and NOD2 mediate P. gingivalis-induced ICAM-1 production in periodontal fibroblasts. NOD1 and NOD2 could be considered potential targets for periodontal therapy.
Porphyromonas gingivalis (P. gingivalis) is one of the main periodontal bacteria. This pathogen was reported to enhance monocyte migration and adhesion to endothelial cells in atherosclerosis. The scavenger receptor lectin-like oxidized lowdensity lipoprotein receptor-1 (LOX-1) plays a pivotal role in atherogenesis. The aim of this study was to investigate whether LOX-1 modulates P. gingivalis-mediated monocyte migration and adhesion to endothelial cells and how it works. The results showed that the migration and adhesion of monocytic THP-1 cells to human umbilical vein endothelial cells (HUVECs) were significantly enhanced when HUVECs or THP-1 cells were challenged with P. gingivalis. Meanwhile, the expression level of LOX-1 in both HUVECs and THP-1 cells were also significantly increased by P. gingivalis stimulation. It is well known that ligand/receptor pairs monocyte chemoattractant protein-1 (MCP-1)/CC chemokine receptor 2 (CCR2), selectins/Integrins, and cell adhesion molecules (CAMs)/Integrins mediate monocyte migration and adhesion to endothelial cells. In this study, LOX-1 was demonstrated to be crucially involved in P. gingivalis-induced THP-1 cell migration and adhesion to HUVECs, by regulating expression of ligands MCP-1, intercellular adhesion molecule-1 (ICAM-1) and E-selectin in HUVECs and that of their receptors CCR2 and Integrin αMβ2 in THP-1 cells. The nuclear factor-kappa B (NF-κB) signaling pathway was proved to be involved in this process. In conclusion, LOX-1 plays a crucial role in P. gingivalis-induced monocyte migration and adhesion to endothelial cells. This result implies LOX-1 may act as a bridge in linking periodontitis to atherosclerosis.
Background
Based on the 2018 classification, we aimed to determine the prevalence, distribution, and progression of periodontitis in the rural Chinese population without access to dental care.
Methods
In all, 404 subjects (28.7 ± 8.9 years, M:F = 182:222) were randomly enrolled in 1992 and re‐called in 1996. With the new classification, the prevalence and distribution of stage, grade, and extent were characterized. Stage progression was compared with the progression of clinical attachment loss (CAL) and radiographic bone loss (RBL).
Results
At baseline, 94.1% villagers suffered from periodontitis, of whom 53.7% were in Stage III/IV. The prevalence of Stage III/IV increased from 18.2% in the age group of 15 to 24 years to 60.9% in 25 to 34‐year‐old group and 88.7% in the 35 to 44‐year‐old group. Significantly more Stage III/IV, generalized, and Grade C periodontitis were found in male villagers than female villagers. In 1996, the prevalence rate of periodontitis increased to 98.5%, with 80.0% in Stage III/IV. Further, 84.2% villagers presented with Grade C periodontitis based on longitudinal ΔCAL. The rate of progression (≥1 site with ΔCAL ≥3 mm) was 63.7%. Stage progression correlated significantly with CAL and RBL progression in Stage I/II, but this association was not found in Stage III/IV. Among subjects with disease progression in Stage III/IV, 90.4% shifted from localized to generalized cases. Furthermore, ceiling effects were observed in Stage III/IV.
Conclusions
In villagers without access to dental care, 94.1% suffered from periodontitis, with more than half having Stage III/IV disease based on the 2018 classification. The majority cases presented with rapid periodontal progression. Although stage progression correlated significantly with CAL and RBL progression in Stage I/II, ceiling effects existed in Stage III/IV.
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