Comprehensive analysis of DNA methylation for periodontitis.

BACKGROUND: Periodontitis is an infectious disease, and a risk factor for peri-implantitis that could result in the implant loss. DNA methylation has an essential role in the etiology and pathogenesis of inflammatory disease. However, there is lack of study on methylation status of genes in periodontitis. This study sought to explore the gene methylation profiling microarray in periodontitis. METHODS: Through searching in the Gene Expression Omnibus database, a gene methylation profiling data set GSE173081 was identified, which included 12 periodontitis samples and 12 normal samples, respectively. Thereafter, the data of GSE173081 was downloaded and analyzed to determined differentially methylated genes (DMGs), which then were used to perform Gene Ontology analysis and pathway enrichment analyses through online database. In addition, the DMGs were applied to construct the protein-protein interaction (PPI) network information, predict the hub genes in pathology of periodontitis. RESULTS: In total 668 DMGs were sorted and identified from the data set, which included 621 hypo-methylated genes and 47 hyper-methylated genes. Through the function and ontology analysis, these 668 genes are mainly classified into intracellular signaling pathway, cell components, cell-cell interaction, and cellular behaviors. The pathway analysis showed that the hypo-methylated genes were mostly enriched in the pathway of cGMP-PKG signaling pathway; RAF/MAP kinase; PI3K-Akt signaling pathway, while hyper-methylated genes were mostly enriched in the pathway of bacterial invasion of epithelial cells; sphingolipid signaling pathway and DCC mediated attractive signaling. The PPI network contained 630 nodes and 1790 interactions. Moreover, further analysis identified top 10 hub genes (APP; PAX6; LPAR1; WNT3A; BMP2; PI3KR2; GATA4; PLCB1; GATA6; CXCL12) as central nodes that are involved in the immune system and the inflammatory response. CONCLUSIONS: This study provides comprehensive information of methylation status of genes to the revelation of periodontitis pathogenesis that may contribute to future research on periodontitis.

Distinct gene expression characteristics in epithelial cell-Porphyromonas gingivalis interactions by integrating transcriptome analyses.

Porphyromonas gingivalis is a pivotal periodontal pathogen, and the epithelial cells serve as the first physical barrier to defend the host from bacterial attack. Within this host-bacteria interaction, P. gingivalis can modify the host immune reaction and adjust the gene expression, which is associated with periodontitis pathogenesis and developing strategies. Herein, a meta-analysis was made to get the differential gene expression profiles in epithelial cells with or without P. gingivalis infection. The network-based meta-analysis program for gene expression profiling was used. Both the gene ontology analysis and the pathway enrichment analysis of the differentially expressed genes were conducted. Our results determined that 290 genes were consistently up-regulated in P. gingivalis infected epithelial cells. 229 gene ontology biological process terms of up-regulated genes were discovered, including "negative regulation of apoptotic process" and "positive regulation of cell proliferation/migration/angiogenesis". In addition to the well-known inflammatory signaling pathways, the pathway associated with a transcriptional misregulation in cancer has also been increased. Our findings indicated that P. gingivalis benefited from the survival of epithelial cells, and got its success as a colonizer in oral epithelium. The results also suggested that infection of P. gingivalis might contribute to oral cancer through chronic inflammation. Negative regulation of the apoptotic process and transcriptional misregulation in cancer pathway are important contributors to the cellular physiology changes during infection development, which have particular relevance to the pathogenesis and progressions of periodontitis, even to the occurrence of oral cancer.

The Additional Effect of Autologous Platelet Concentrates to Coronally Advanced Flap in the Treatment of Gingival Recessions: A Systematic Review and Meta-Analysis.

BACKGROUND: To improve the efficacy of regenerative treatment for gingival recessions, the autologous platelet concentrates (APCs) combined with coronally advanced flap (CAF) have been investigated. However, few studies systematically assess the complementary effect of APCs in periodontal regeneration. The present study aims to evaluate the additional effect of different types of APCs to CAF in the treatment of gingival recessions. METHODS: Electronic databases (EMBASE, MEDLINE, and Cochrane Central Register of Controlled Trails) and relevant journals were searched until May 15, 2019. Only randomized controlled trials (RCTs) in English were included. Outcome variables include root coverage (RC), recession depth (RD), clinical attachment level (CAL), keratinized tissue width (KTW), and gingival thickness (GT). Data were analyzed with Revman5.3. The estimate of effect sizes was expressed as the mean differences and the 95% confidence interval. RESULTS: 8 RCTs involving 170 patients (328 sites) were included. Our meta-analysis indicated RC, RD, CAL, KTW, and GT were better improved in the CAF plus APCs groups than the CAF alone. The subgroup analyses revealed that platelet-rich fibrin (PRF) brought significant improvement in RC, RD, CAL, and GT. Concentrated growth factors (CGF) lead clinic beneficial in CAL, KTW, and GT. No significant effect of platelet-rich plasma (PRP) could be found in any clinical parameters when combined with CAF. CONCLUSIONS: PRF could exert additional effect to CAF; the preferred treatment for gingival recessions was considered. Based on the limited studies, it seemed that PRP failed to show any additional effect and it was not suggested for gingival recessions. Given the limited research and high risk of bias, it is still needed to confirm the additional effect of CGF by more high-quality studies.

Effect of platelet-rich fibrin on alveolar ridge preservation: A systematic review.

BACKGROUND: Platelet-rich fibrin (PRF) is the second generation of platelet concentrates and is used in many areas of dentistry. However, whether PRF is effective for alveolar ridge preservation remains controversial. The authors conducted research to evaluate the potential of PRF to preserve the alveolar ridge. METHODS: A comprehensive literature search was conducted in MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. Only randomized controlled trials were included. A systematic review was made for postoperative pain, soft-tissue healing, bone density, horizontal and vertical ridge dimension changes, and histologic analysis. The meta-analysis was performed on the alveolar osteitis, mesial and distal bone height changes, and bone fill with Review Manager Version 5.3 software. RESULTS: Among the 588 eligible articles found in the initial search, 7 published studies from 2012 through 2019 were included. The authors' qualitative analysis showed that PRF may play a positive role in reducing postoperative pain and ridge dimension changes after tooth extraction. Among the 7 articles, only 2 trials assessed the effect of PRF on the alveolar osteitis, mesial and distal bone height changes, and bone fill. Results of our meta-analysis showed that smaller mesial bone height changes (standard mean difference, -1.07; 95% confidence interval, -1.92 to 0.22) and a greater percentage of bone fill (standard mean difference, 0.82; 95% confidence interval, 0.32 to 1.33) were observed in the PRF group. CONCLUSIONS: Given the potential value of PRF, consideration should be given to PRF after tooth extraction. However, more high-quality trials are necessary to evaluate the exact role of PRF. PRACTICAL IMPLICATIONS: Based on the authors' results, the usage of PRF was suggested in alveolar ridge preservation.

The expression of macrophage migration inhibitory factor and intercellular adhesion molecule-1 in rats with periodontitis and atherosclerosis.

OBJECTIVE: The aim of this study was to explore the role of macrophage migration inhibitory factor (MIF) and intercellular adhesion molecule (ICAM)-1 in rats with periodontitis and atherosclerosis. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into 4 groups: control group (C), periodontitis group (P), atherosclerosis group (AS), and periodontitis plus atherosclerosis group (P + AS). The levels of MIF and ICAM-1 in serum were detected by an enzyme-linked immunosorbent assay (ELISA). The protein expression of MIF and ICAM-1 in the carotid artery tissues was examined by immunohistochemical staining. RESULTS: The results of the ELISA showed that the serum level of MIF in the P + AS group (59.40 ±â€¯3.92 ng/mL) was significantly higher than that in the C group (42.93 ±â€¯2.63 ng/mL), the P group (45.57 ±â€¯2.59 ng/mL) and the AS group (50.88 ±â€¯4.20 ng/mL) (P < 0.05). Similarly, the ICAM-1 level in the P + AS group (6.77 ±â€¯1.47 ng/mL) was much higher than that in the C (1.33 ±â€¯0.25 ng/mL), P (3.99 ±â€¯0.44 ng/mL) and AS groups (4.19 ±â€¯0.89 ng/mL) (P < 0.05). Furthermore, the expression of MIF, as assessed by immunohistochemical staining, was significantly higher in the artery tissues of the P + AS group than in the tissues of the other three groups (P < 0.05). However, there was no significant difference in the protein level of ICAM-1 between the P + AS and AS groups, where its expression was much stronger than in the C and the P groups. CONCLUSION: Our results indicate that there is a close association between periodontitis and atherosclerosis. MIF and ICAM-1 may play a role in the development of atherosclerosis and periodontitis.

Porphyromonas gingivalis-Induced MIF Regulates Intercellular Adhesion Molecule-1 Expression in EA.hy926 Cells and Monocyte-Endothelial Cell Adhesion Through the Receptors CD74 and CXCR4.

Porphyromonas gingivalis (P. gingivalis) is an important pathogen that contributes to periodontal disease and causes infections that promote the progression of atherosclerosis. Our previous studies showed that macrophage migration inhibitory factor (MIF) facilitates monocyte adhesion to endothelial cells by regulating the expression of intercellular adhesion molecule-1 (ICAM-1) in P. gingivalis-infected endothelial cells. However, the detailed pathological role of MIF has yet to be elucidated in this context. To explore the functional receptor(s) of MIF that underlie its participation in the pathogenesis of atherosclerosis, we investigated the expression of the chemokine receptors CD74 and CXCR4 in endothelial cells, both of which were shown to be involved in the adhesion of monocytes to endothelial cells pretreated with P. gingivalis. Furthermore, the formation of a MIF, CD74, and CXCR4 ligand-receptor complex was revealed by our immunofluorescence staining and coimmunoprecipitation results. By interacting with the CD74/CXCR4 receptor complex, MIF may act as a crucial regulator of monocyte-endothelial cell adhesion and promote the atherosclerotic plaque formation induced by P. gingivalis.

Porphyromonas gingivalis ATCC 33277 promotes intercellular adhesion molecule-1 expression in endothelial cells and monocyte-endothelial cell adhesion through macrophage migration inhibitory factor.

BACKGROUND: Porphyromonas gingivalis (P. gingivalis), one of the main pathogenic bacteria involved in periodontitis, induces the expression of intercellular adhesion molecule - 1 (ICAM-1) and monocyte-endothelial cell adhesion. This effect plays a pivotal role in atherosclerosis development. Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine and critically affects atherosclerosis pathogenesis. In this study, we tested the involvement of MIF in the P. gingivalis ATCC 33277-enhanced adhesive properties of endothelial cells. RESULTS: Endothelial MIF expression was enhanced by P. gingivalis ATCC 33277 infection. The MIF inhibitor ISO-1 inhibited ICAM-1 production in endothelial cells, and monocyte-endothelial cell adhesion was induced by P. gingivalis ATCC 33277 infection. However, the addition of exogenous human recombinant MIF to P. gingivalis ATCC 33277-infected endothelial cells facilitated monocyte recruitment by promoting ICAM-1 expression in endothelial cells. CONCLUSIONS: These experiments revealed that MIF in endothelial cells participates in the pro-atherosclerotic lesion formation caused by P. gingivalis ATCC 33277 infection. Our novel findings identify a more detailed pathological role of P. gingivalis ATCC 33277 in atherosclerosis.