The gingival epithelium is a physical and immunological barrier to the microbiota of the oral cavity, which interact through soluble mediators with the immune cells that patrol the tissue at the ...gingival epithelium. We sought to develop a three-dimensional gingivae-biofilm interface model using a commercially available gingival epithelium to study the tissue inflammatory response to oral biofilms associated with "health", "gingivitis" and "periodontitis". These biofilms were developed by sequential addition of microorganisms to mimic the formation of supra- and sub-gingival plaque in vivo. Secondly, to mimic the interactions between gingival epithelium and immune cells in vivo, we integrated peripheral blood mononuclear cells and CD14
monocytes into our three-dimensional model and were able to assess the inflammatory response in the immune cells cultured with and without gingival epithelium. We describe a differential inflammatory response in immune cells cultured with epithelial tissue, and more so following incubation with epithelium stimulated by "gingivitis-associated" biofilm. These results suggest that gingival epithelium-derived soluble mediators may control the inflammatory status of immune cells in vitro, and therefore targeting of the epithelial response may offer novel therapies. This multi-cellular interface model, both of microbial and host origin, offers a robust in vitro platform to investigate host-pathogens at the epithelial surface.
The administration of several classes of drugs can lead to the onset of gingival overgrowth: anticonvulsants, immunosuppressants, and calcium channel blockers. Among the anticonvulsants, the main ...drug associated with gingival overgrowth is diphenylhydantoin.
In this study, we compared the effects of diphenylhydantoin and gabapentin on 57 genes belonging to the "Extracellular Matrix and Adhesion Molecule" pathway, present in human fibroblasts of healthy volunteers.
Both molecules induce the same gene expression profile in fibroblasts as well as a significant upregulation of genes involved in extracellular matrix deposition like COL4A1, ITGA7, and LAMB3. The two treatments also induced a significant downregulation of genes involved in the expression of extracellular matrix metalloproteases like MMP11, MMP15, MMP16, MMP24, and transmembrane receptor ITGB4.
Data recorded in our study confirmed the hypothesis of a direct action of these drugs at the periodontium level, inducing an increase in matrix production, a reduction in its degradation, and consequently resulting in gingival hyperplasia.
Background
Defining periodontal health has been an ambitious and complex goal. The numerous and varied definitions of what constitutes periodontal health have resulted in a collection of subjective ...and unreliable clinical findings to diagnose and classify periodontal health and disease. The aim of this study was to fundamentally delineate the molecular characteristics of healthy periodontal tissues in men and women as they age, using the most abundant connective tissue component: Collagens.
Methods
Healthy gingival biopsies were separated into “young” (aged 18–35 years, five men/five women) and “old” (≥60 years, five men/four women) age groups depending on biological sex. RNA was extracted and next‐generation RNA sequencing was performed using Unique Molecular Identifiers. Collagen gene expression was determined and quantified for young and old, male and female individuals.
Results
Twenty‐six human collagens were identified in healthy gingival tissues. In general, age and biological sex affected expression of collagen α‐chain transcripts. Ten of the 26 human gingival collagen genes formed a unique pattern for gingival health. More specifically, the expression of fibrillary (types I and III), fibril‐associated collagens with interrupted triple‐helices (FACIT) and FACIT‐like (types XII, XIV, and XX), network‐forming (types IV and VI), transmembrane (type XVII), and multiplexin (types XV and XVIII) collagens, taken together, exhibited a distinct pattern of characteristics for gingival health that was independent of age or biological sex.
Conclusions
Although specific α‐chains of the collagen transcriptome were affected by age and biological sex, the compilation of various collagen transcripts can be used to define gingival health that is independent of age and biological sex.
γδT cells are a major component of epithelial tissues and play a role in tissue homeostasis and host defense. γδT cells also reside in the gingiva, an oral tissue covered with specialized epithelium ...that continuously monitors the challenging dental biofilm. Whereas most research on intraepithelial γδT cells focuses on the skin and intestine epithelia, our knowledge on these cells in the gingiva is still incomplete. In this study, we demonstrate that even though the gingiva develops after birth, the majority of gingival γδT cells are fetal thymus-derived Vγ6⁺ cells, and to a lesser extent Vγ1⁺ and Vγ4⁺ cells. Furthermore, we show that γδT cells are motile and locate preferentially in the epithelium adjacent to the biofilm. Vγ6⁺ cells represent the major source of IL-17–producing cells in the gingiva. Chimeric mice and parabiosis experiments indicated that the main fraction of gingival γδT cells is radioresistant and tissue-resident, persisting locally independent of circulating γδT cells. Notably, gingival γδT cell homeostasis is regulated by the microbiota as the ratio of Vγ6⁺ and Vγ4⁺ cells was reversed in germ-free mice, and their activation state was decreased. As a consequence, conditional ablation of γδT cells results in elevated gingival inflammation and subsequent alterations of oral microbial diversity. Taken together, these findings suggest that oral mucosal homeostasis is shaped by reciprocal interplays between γδT cells and local microbiota.
Objectives
To evaluate gingiva‐colored resin‐based composites' (GCRBC) color stability and degree of conversion (DC%).
Methods
Eight discs (8 × 1 mm) of 20 shades of GCRBC were prepared. Color ...coordinates were measured against a gray background with a calibrated spectroradiometer, CIE D65 illuminant and the CIE 45°/0° geometry at baseline and after 30 days of storage in distilled water, coffee, and red wine. Color differences (∆E00) between final and baseline conditions were calculated. An ATR‐FTIR spectrometer with a diamond tip was used to calculate DC%. The results were analyzed statistically using ANOVA and Tukey post‐hoc test. The level of significance was p < 0.05.
Results
DC% and color stability correlated with each other and with the GCRBC brand. DC% ranged between 43% and 96%, highest values correspond to flowable composites. All composites have experienced color changes after immersion in water, wine and coffee. However, the magnitude of the color change has varied widely depending on the immersion medium and the GCRBC. Color changes generated by the wine were, globally, greater than those induced by coffee (p < 0.001) and above the acceptability thresholds.
Conclusions
The DC% of GCRBCs is sufficient to achieve adequate biocompatibility and physicomechanical properties, but the high susceptibility to staining could compromise aesthetic long‐term results.
Clinical Significance
The degree of conversion and the color stability of gingiva‐colored resin‐based composites correlated with each other. All composites have experienced color changes after immersion in water, wine and coffee. Color changes generated by wine were, globally, greater than those induced by coffee and above the acceptability thresholds that could compromise aesthetic long‐term results.
Background: Gingival augmentation procedures around natural teeth and dental implants are performed to facilitate plaque control, to improve patient comfort, to prevent future recession, and in ...conjunction with restorative, orthodontic, or prosthetic dentistry. The aim of this study is to answer the most common questions related to this treatment modality based on the most relevant and current knowledge in the field.
Methods: Two reviewers worked to answer the five most common and clinically relevant questions with supporting literature to understand the role of gingiva around teeth. 1) What circumstances require an increased zone of keratinized tissue (KT), or is KT important? 2) What is the ideal thickness of an autogenous gingival graft? Is a thick autogenous gingival graft more effective than a thin autogenous gingival graft? 3) What are the alternatives to autogenous gingival grafting to increase the zone of attached gingiva? 4) Does orthodontic intervention affect soft tissue health and dimensions? 5) What is the patient‐reported patient outcome for minimal KT compared with that for an enhanced zone of KT? An extensive literature search was performed using PubMed, the Cochrane Oral Health Group Specialized Trials Registry (the Cochrane Library), and the most respected journals in the field.
Results: Although gingival augmentation procedures were first introduced in 1960s, there have not been in‐depth comparative studies examining the five questions that have been proposed by the authors. Lack of relevant systematic reviews and randomized clinical trials (RCTs) on this topic do not allow authors to answer those questions with a strong level of evidence. However, the following can be recommended after reviewing case reports and case series on these topics. 1) There is enough clinical evidence to support maintaining an adequate band of gingiva for intracrevicular margin restoration. 2) Thick grafts do not appear to result in better clinical outcomes than thin grafts. Thick grafts are likely to result in more primary contraction, whereas thin grafts tend to be prone to secondary contraction. 3) Viable alternative treatment modalities are currently available that are capable of providing KT augmentation without the need for palatal donor tissue. 4) Appropriately applied orthodontic forces do not cause permanent damage to a healthy periodontium. The probability of recession during tooth movement in thin biotype is high to justify gingival augmentation when the dimension of gingiva is inadequate. In addition, cases in which there will be a facial tooth movement outside of the alveolar process need to be considered for a gingival augmentation procedure. 5) Although the articles that have been published on this topic did not consider patient‐reported outcomes and esthetics as part of the overall treatment success assessment, patients who have received alternative treatment modalities that did not depend on palatal tissue harvesting appear to have reported more satisfaction and less discomfort after treatment.
Conclusions: Autogenous gingival grafts are still considered to be the “gold standard” procedure with unmatched success rates and clinical success when gingival augmentation procedures are required. However, tissue‐engineered materials may offer viable options to palatal tissue harvesting for gingival augmentation. KT augmentation may prevent the development and progression of gingival recession, especially when restorative margins may interact with the periodontium and/or orthodontic treatment is indicated. Patient‐reported outcomes should be considered for future studies on this topic. Additional RCTs and systematic reviews are needed to support these conclusions.
An increased prevalence of periodontitis and perturbation of the oral microbiome has been identified in patients with rheumatoid arthritis (RA). The periodontal pathogen
may cause local ...citrullination of proteins, potentially triggering anti-citrullinated protein antibody production. However, it is not known if oral dysbiosis precedes the onset of clinical arthritis. This study comprehensively characterised the oral microbiome in anti-cyclic citrullinated peptide (anti-CCP) positive at-risk individuals without clinical synovitis (CCP+at risk).
Subgingival plaque was collected from periodontally healthy and diseased sites in 48 CCP+at risk, 26 early RA and 32 asymptomatic healthy control (HC) individuals. DNA libraries were sequenced on the Illumina HiSeq 3000 platform. Taxonomic profile and functional capability of the subgingival microbiome were compared between groups.
At periodontally healthy sites, CCP+at risk individuals had significantly lower microbial richness compared with HC and early RA groups (p=0.004 and 0.021). Microbial community alterations were found at phylum, genus and species levels. A large proportion of the community differed significantly in membership (523 species; 35.6%) and structure (575 species; 39.1%) comparing CCP+at risk and HC groups. Certain core species, including
, had higher relative abundance in the CCP+at risk group. Seventeen clusters of orthologous gene functional units were significantly over-represented in the CCP+at risk group compared with HC (adjusted p value <0.05).
Anti-CCP positive at-risk individuals have dysbiotic subgingival microbiomes and increased abundance of
compared with controls. This supports the hypothesis that the oral microbiome and specifically
are important in RA initiation.
The subgingival biofilm attached to tooth surfaces triggers and maintains periodontitis. Previously, late-onset periodontitis has been considered a consequence of dysbiosis and a resultant ...polymicrobial disruption of host homeostasis. However, a multitude of studies did not show "healthy" oral microbiota pattern, but a high diversity depending on culture, diets, regional differences, age, social state etc. These findings relativise the aetiological role of the dysbiosis in periodontitis. Furthermore, many late-onset periodontitis traits cannot be explained by dysbiosis; e.g. age-relatedness, attenuation by anti-ageing therapy, neutrophil hyper-responsiveness, and microbiota shifting by dysregulated immunity, yet point to the crucial role of dysregulated immunity and neutrophils in particular. Furthermore, patients with neutropenia and neutrophil defects inevitably develop early-onset periodontitis. Intra-gingivally injecting lipopolysaccharide (LPS) alone causes an exaggerated neutrophil response sufficient to precipitate experimental periodontitis. Vice versa to the surplus of LPS, the increased neutrophil responsiveness characteristic for late-onset periodontitis can effectuate gingiva damage likewise. The exaggerated neutrophil extracellular trap (NET) response in late-onset periodontitis is blameable for damage of gingival barrier, its penetration by bacteria and pathogen-associated molecular patterns (PAMPs) as well as stimulation of Th17 cells, resulting in further neutrophil activation. This identifies the dysregulated immunity as the main contributor to periodontal disease.
Objective
Idiopathic gingival fibromatosis (IGF) is a rare heterogeneous disease that results in the progressive and diffuse hyperplasia of gingival tissues. MicroRNAs are implicated in the ...development and progression of various tumors. The present study aimed to explore the potential roles and mechanisms of miR‐148a‐3p in IGF.
Methods
Gingival fibroblasts (GFs) were transfected with miR‐148a‐3p mimics, miR‐148a‐3p inhibitors, or siNPTX1, and then, the proliferation and apoptosis of GFs and the expression of related genes were evaluated using Cell Counting Kit‐8 assays, 5‐ethynyl‐2′‐deoxyuridine assays, flow cytometry, reverse transcription‐quantitative polymerase chain reaction, and western blot analysis, respectively.
Results
miR‐148a‐3p was highly expressed in GFs of IGF (IGF‐GFs) as compared with normal GFs (N‐GFs). Overexpression of miR‐148a‐3p promoted the proliferation and inhibited the apoptosis of N‐GFs, whereas downregulation of miR‐148a‐3p had the opposite effect in IGF‐GFs. Knockdown of NPTX1 reversed miR‐148a‐3p‐mediated effects in IGF‐GFs. Dual‐luciferase reporter assay confirmed that NPTX1 is a direct target of miR‐148a‐3p.
Conclusion
These findings identify that miR‐148a‐3p could regulate cell proliferation and apoptosis by targeting NPTX1, providing new insights for the further study of the molecular mechanism and treatment of IGF.
Abstract Although nanoparticles (NPs) has afforded considerable benefits in various fields of sciences, several reports have shown their harmful effects, suggesting the necessity of adequate risk ...assessment. To clarify the mechanism of titanium dioxide nanoparticles (TiO2 NPs)-enhanced gingival inflammation, we conducted the full-scale metabolomic analyses of human gingival fibroblast cells treated with IL-1β alone or in combination with TiO2 NPs. Observation with transmission electron microscope demonstrated the incorporation of TiO2 NPs into vacuoles of the cells. TiO2 NPs significantly enhanced the IL-1β-induced prostaglandin E2 production and COX-1 and COX-2 protein expression. IL-1β reduced the intracellular concentrations of overall primary metabolites especially those of amino acid, urea cycle, polyamine, S -adenosylmethione and glutathione synthetic pathways. The addition of TiO2 NPs further augmented these IL-1β-induced metabolic changes, recommending careful use of dental materials containing TiO2 NPs towards patients with gingivitis or periodontitis. The impact of the present study is to identify the molecular targets of TiO2 NPs for the future establishment of new metabolic markers and therapeutic strategy of gingival inflammation.
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