Summary
Fusobacterium nucleatum is an invasive anaerobic bacterium that is associated with periodontal disease. Previous studies have focused on virulence factors produced by F. nucleatum, but early ...recognition of the pathogen by the immune system remains poorly understood. Although an inflammasome in gingival epithelial cells (GECs) can be stimulated by danger‐associated molecular patterns (DAMPs) (also known as danger signals) such as ATP, inflammasome activation by this periodontal pathogen has yet to be described in these cells. This study therefore examines the effects of F. nucleatum infection on pro‐inflammatory cytokine expression and inflammasome activation in GECs. Our results indicate that infection induces translocation of NF‐κB into the nucleus, resulting in cytokine gene expression. In addition, infection activates the NLRP3 inflammasome, which in turn activates caspase‐1 and stimulates secretion of mature IL‐1β. Unlike other pathogens studied until now, F. nucleatum activates the inflammasome in GECs in the absence of exogenous DAMPs such as ATP. Finally, infection promotes release of other DAMPs that mediate inflammation, such as high‐mobility group box 1 protein and apoptosis‐associated speck‐like protein, with a similar time‐course as caspase‐1 activation. Thus, F. nucleatum expresses the pathogen‐associated molecular patterns necessary to activate NF‐κB and also provides an endogenous DAMP to stimulate the inflammasome and further amplify inflammation through secretion of secondary DAMPs.
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Periodontal diseases remain a challenge due to a complex interplay of factors involving a chronic inflammatory activation and bacteria internalization in periodontal cells. In this ...work, chitosan-nanoparticles loaded with minocycline (MH-NPs), a tetracycline with antimicrobial and anti-inflammatory effects, were developed for in situ delivery in the periodontal milieu aiming to improve drug effectiveness.
A general cytocompatibility evaluation and a detailed approach to address the cellular uptake process, trafficking pathways and the modulation of relevant inflammatory gene expression was conducted using human gingival fibroblasts. Results show that MH-NPs with an adequate cytocompatible profile can be internalized by distinct endocytic processes (macropinocytosis and clathrin-mediated endocytosis). The ability to modulate autophagy with the delivery within the same endosomal/lysosomal pathway as periodontal pathogens was observed, which increases the intracellular drug effectiveness. Porphyromonas gingivalis LPS-stimulated cultures, grown in the presence of MH-NPs, were found to express significantly reduced levels of inflammation-related markers (IL-1b, TNFα, CXCL-8, NFKB1). These nanoparticles can be potentially used in periodontal disease treatment conjoining the ability of intracellular drug targeting with significant anti-inflammatory effects.
The focus of this study was to determine which chemokine receptors are present on oral fibroblasts and whether these receptors influence proliferation, migration, and/or the release of wound healing ...mediators. This information may provide insight into the superior wound healing characteristics of the oral mucosa. The gingiva fibroblasts expressed 12 different chemokine receptors (CCR3, CCR4, CCR6, CCR9, CCR10, CXCR1, CXCR2, CXCR4, CXCR5, CXCR7, CX3CR1, and XCR1), as analyzed by flow cytometry. Fourteen corresponding chemokines (CCL5, CCL15, CCL20, CCL22, CCL25, CCL27, CCL28, CXCL1, CXCL8, CXCL11, CXCL12, CXCL13, CX3CL1, and XCL1) were used to study the activation of these receptors on gingiva fibroblasts. Twelve of these fourteen chemokines stimulated gingiva fibroblast migration (all except for CXCL8 and CXCL12). Five of the chemokines stimulated proliferation (CCL5/CCR3, CCL15/CCR3, CCL22/CCR4, CCL28/CCR3/CCR10, and XCL1/XCR1). Furthermore, CCL28/CCR3/CCR10 and CCL22/CCR4 stimulation increased IL‐6 secretion and CCL28/CCR3/CCR10 together with CCL27/CCR10 upregulated HGF secretion. Moreover, TIMP‐1 secretion was reduced by CCL15/CCR3. In conclusion, this in‐vitro study identifies chemokine receptor‐ligand pairs which may be used in future targeted wound healing strategies. In particular, we identified the chemokine receptors CCR3 and CCR4, and the mucosa specific chemokine CCL28, as having an predominant role in oral wound healing by increasing human gingiva fibroblast proliferation, migration, and the secretion of IL‐6 and HGF and reducing the secretion of TIMP‐1.
Gingiva fibroblasts express 12 chemokine receptors. Fourteen chemokines were used to study proliferation (top), migration (middle), and secretion of wound healing mediators by gingiva fibroblasts (bottom). Predominantly CCR3 and CCR4 stimulation influenced these oral wound healing parameters.
Background: Management of gingival recession defects, a common periodontal condition, using root coverage procedures is an important aspect of periodontal regenerative therapy. The goal of the ...periodontal soft tissue root coverage procedures group was to develop a consensus report based on the accompanying systematic review of root coverage procedures, including priorities for future research and identification of the best evidence available to manage different clinical scenarios.
Methods: The group reviewed and discussed the accompanying systematic review, which covered treatment of single‐tooth recession defects, multiple‐tooth recession defects, and additional focused questions on relevant clinical topics. The consensus group members submitted additional material for consideration by the group in advance and at the time of the meeting. The group also identified priorities for future research.
Results: All reviewed root coverage procedures provide significant reduction in recession depth, especially for Miller Class I and II recession defects. Subepithelial connective tissue graft (SCTG) procedures provide the best root coverage outcomes. Acellular dermal matrix graft (ADMG) or enamel matrix derivative (EMD) in conjunction with a coronally advanced flap (CAF) can serve as alternatives to autogenous donor tissue. Additional research is needed to do the following: 1) assess the treatment outcomes for multiple‐tooth recession defects, oral sites other than maxillary canine and premolar teeth, and Miller Class III and IV defects; 2) assess the role of patient‐ and site‐specific factors on procedure outcomes; and 3) obtain evidence on patient‐reported outcomes.
Conclusions: Predictable root coverage is possible for single‐tooth and multiple‐tooth recession defects, with SCTG procedures providing the best root coverage outcomes. Alternatives to SCTG are supported by evidence of varying strength. Additional research is needed on treatment outcomes for specific oral sites.
Clinical Recommendation: For Miller Class I and II single‐tooth recession defects, SCTG procedures provide the best outcomes, whereas ADMG or EMD in conjunction with CAF may be used as an alternative.
Several proteins and peptides in saliva were shown to stimulate gingival wound repair, but the role of salivary metabolites in this process remains unexplored. In vitro gingival re-epithelialization ...kinetics were determined using unstimulated saliva samples from healthy individuals collected during an experimental gingivitis study. Elastic net regression with stability selection identified a specific metabolite signature in a training dataset that was associated with the observed re-epithelialization kinetics and enabled its prediction for all saliva samples obtained in the clinical study. This signature encompassed ten metabolites, including plasmalogens, diacylglycerol and amino acid derivatives, which reflect enhanced host-microbe interactions. This association is in agreement with the positive correlation of the metabolite signature with the individual's gingival bleeding index. Remarkably, intra-individual signature-variation over time was associated with elevated risk for gingivitis development. Unravelling how these metabolites stimulate wound repair could provide novel avenues towards therapeutic approaches in patients with impaired wound healing capacity.
The key to achieving pleasing esthetics in implant dentistry is a thorough understanding of the biological processes driving dimensional bone and soft tissue alterations post‐extraction. The aim of ...the present report is first to characterize the extent of bone and soft tissue changes post‐extraction and second to identify potential factors influencing tissue preservation in order to facilitate successful treatment outcomes. The facial bone wall thickness has been identified as the most critical factor influencing bone resorption and can be used as a prognostic tool in order to identify sites at risk for future facial bone loss subsequent to tooth extraction. Clinical studies indicated that thin bone wall phenotypes exhibiting a facial bone wall thickness of 1 mm or less revealed progressive bone resorption with a vertical loss of 7.5 mm, whereas thick bone wall phenotypes showed only minor bone resorption with a vertical loss of 1.1 mm. This is in contrast to the dimensional soft tissue alterations. Thin bone wall phenotypes revealed a spontaneous soft tissue thickening after flapless extraction by a factor of seven, whereas thick bone wall phenotypes showed no significant changes in the soft tissue dimensions after 8 weeks of healing. In sites exhibiting a limited bone resorption rate, immediate implant placement may be considered. If such ideal conditions are not present, other timing protocols are recommended to achieve predictable and pleasing esthetics. Socket preservation techniques for ridge preservation utilizing different biomaterials and/or barrier membranes often result in a better maintenance of tissue volumes, although the inevitable biological process of post‐extraction bone resorption and bone modeling cannot be arrested. In summary, the knowledge of the biological events driving dimensional tissue alterations post‐extraction should be integrated into the comprehensive treatment plan in order to limit tissue loss and to maximize esthetic outcomes.
Periodontitis is an inflammatory disease that can lead to the periodontal pocket formation and tooth loss. This study was aimed to develop antimicrobials loaded hydrogels composed of cellulose ...nanofibers (CNF) and κ-carrageenan oligosaccharides (CO) nanoparticles for the treatment of periodontitis. Two antimicrobial agents such as surfactin and Herbmedotcin were selected as the therapeutic agents and the hydrogels were formulated based on the increasing concentration of surfactin. The proposed material has high thermal stability, controlled release, and water absorption capacity. This study was proceeded by investigating the in vitro antibacterial and anti-inflammatory properties of the hydrogels. This material has strong antibacterial activity against periodontal pathogens such as Streptococcus mutans, Porphyromonas gingivalis, Fusobacterium nucleatum, and Pseudomonas aeruginosa. Moreover, a significant increase in malondialdehyde (MDA) production and a decrease in biofilm formation and metabolic activity of the bacteria was observed in the presence of hydrogel. Besides, it reduced the reactive oxygen species (ROS) generation, transcription factor, and cytokines production in human gingival fibroblast cells (HGF) under inflammatory conditions. In conclusion, the hydrogels were successfully developed and proven to have antibacterial and anti-inflammatory properties for the treatment of periodontitis. Thus, it can be used as an excellent candidate for periodontitis treatment.
Studies have been focused on natural products with antibacterial and anti-inflammatory activities, such as fucoidan. Many in vivo studies have evaluated the effect of fucoidan on tumor growth, ...diabetes, obesity, ischemia reperfusion, and oxidative stress. However, the effects of fucoidan on bacteria-induced gingival inflammation and periodontitis have not been reported. We previously characterized the anti-inflammatory effect of fucoidan in vitro. Here, we confirmed the anti-inflammatory activity of fucoidan in a macrophage cell line in terms of its inhibition of the expression of inflammatory mediators and pro-inflammatory cytokines. Additionally, we confirmed the ability of fucoidan to inhibit gingival inflammation, expression of pro-inflammatory cytokines, and neutrophil recruitment in the gingival tissue of mice injected with LPS prepared from P. gingivalis. Interestingly, however, fucoidan did not inhibit the expression of pro-inflammatory cytokines in a P. gingivalis-infected mouse model of periodontitis. Additionally, fucoidan treatment did not lead to clearance of P. gingivalis or improvement of P. gingivalis infection-mediated bone loss in the periodontitis model. We conclude that fucoidan exerts anti-inflammatory effects in vitro and in vivo, together with a limited antibacterial effect in vivo.
•Effects of fucoidan on bacteria-induced gingival inflammation have not been reported.•We confirmed the anti-inflammatory activity of fucoidan in macrophage cell line.•Fucoidan inhibited inflammation in the gingival tissue of LPS-injected mice.•Fucoidan treatment did not clear P. gingivalis in the periodontitis model.•We conclude that fucoidan exerts anti-inflammatory effects in vitro and in vivo.
Periodontitis is a chronic inflammatory disease induced by
Porphyromonas gingivalis
(
P. gingivalis
) and other pathogens.
P. gingivalis
release various virulence factors including lipopolysaccharide ...(LPS). However, whether
P. gingivalis
–LPS inducing pyroptosis in human gingival fibroblasts (HGFs) remains unknown. In present study,
P. gingivalis
–LPS decreased the membrane integrity of HGFs, and pyroptosis-associated cytokines were upregulated at the mRNA level. In addition, pyroptosis proteins were highly expressed in gingival tissues of periodontitis.
P. gingivalis
–LPS induced gingivitis in the rat model, and the expression level of pyroptosis-associated proteins increased. Together,
P. gingivalis
–LPS can activate the pyroptosis reaction, which may be a pro-pyroptosis status in a relative low concentration.
The goals of this study were to better understand the ecology of oral subgingival communities in health and periodontitis and elucidate the relationship between inflammation and the subgingival ...microbiome. Accordingly, we used 454-pyrosequencing of 16S rRNA gene libraries and quantitative PCR to characterize the subgingival microbiome of 22 subjects with chronic periodontitis. Each subject was sampled at two sites with similar periodontal destruction but differing in the presence of bleeding, a clinical indicator of increased inflammation. Communities in periodontitis were also compared with those from 10 healthy individuals. In periodontitis, presence of bleeding was not associated with different α-diversity or with a distinct microbiome, however, bleeding sites showed higher total bacterial load. In contrast, communities in health and periodontitis largely differed, with higher diversity and biomass in periodontitis. Shifts in community structure from health to periodontitis resembled ecological succession, with emergence of newly dominant taxa in periodontitis without replacement of primary health-associated species. That is, periodontitis communities had higher proportions of Spirochetes, Synergistetes, Firmicutes and Chloroflexi, among other taxa, while the proportions of Actinobacteria, particularly Actinomyces, were higher in health. Total Actinomyces load, however, remained constant from health to periodontitis. Moreover, an association existed between biomass and community structure in periodontitis, with the proportion of specific taxa correlating with bacterial load. Our study provides a global-scale framework for the ecological events in subgingival communities that underline the development of periodontitis. The association, in periodontitis, between inflammation, community biomass and community structure and their role in disease progression warrant further investigation.
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