Periodontal granulation tissue - To remove or not to remove, that is the question.

Formation of granulation tissue is a fundamental phase in periodontal wound healing with subsequent maturation leading to regeneration or repair. However, persistently inflamed granulation tissue presents in osseous defects as a result of periodontitis and is routinely disrupted and discarded with non-surgical and surgical therapy to facilitate wound healing or improve chances of regeneration. Histological assessment suggests that granulation tissue from periodontitis-affected sites is effectively a chronic inflammatory tissue resulting from impaired wound healing due to persistence of bacterial dysbiotic bioflim. Nevertheless, the immunomodulatory potential and stem cell characteristics in granulation tissue have also raised speculation about the tissue's regenerative potential. This has led to the conception and recent implementation of surgical techniques which preserve granulation tissue with the intention of enhancing innate regenerative potential and improve clinical outcomes. As knowledge of fundamental cellular and molecular functions regulating periodontitis-affected granulation tissue is still scarce, this review aimed to provide a summary of current understanding of granulation tissue in the context of periodontal wound healing. This may provide new insights into clinical practice related to the management of granulation tissue and stimulate further investigation.

Elucidating the molecular healing of intrabony defects following non-surgical periodontal therapy: A pilot study.

OBJECTIVE: To elucidate the molecular healing of intrabony defects following non-surgical periodontal therapy (NSPT) using gingival crevicular fluid (GCF). BACKGROUND DATA: Currently limited information is available regarding the GCF of intrabony defects and the change in biomarker levels in the GCF at early time points following treatment interventions. METHODS: Twenty-one patients (Periodontitis Stage III or IV) who have received NSPT, contributing one intrabony defect and one healthy site were included in this study. GCF sampling was performed at baseline, 1 day, 5 days and 3 months after NSPT. Multiplex bead immunoassays allowed the profiling of GCF for 27 markers, associated with inflammation and repair/regeneration. A mixed effects model with Bonferroni correction for multiple comparisons was employed to compare the changes in the levels of GCF markers over time. RESULTS: Following NSPT, changes were observed for several GCF markers, marked by significant increases 1 day post-intervention, before returning to baseline levels by 3 months. Specifically, GCF concentrations of IL-2, IL-4, IL-6, IL-8, MMP-1, MMP-3, TIMP-1 and FGFb significantly increased 1 day after NSPT. Signs of activation of cellular senescence were observed 1 day following treatment of intrabony defects, rapidly regressing by 5 days. CONCLUSION: Significant molecular changes are observed as early as 1 day following NSPT in intrabony defects, along with activation of cellular senescence.

Tooth loss during supportive periodontal care: A prospective study.

AIM: To assess periodontal stability and the association between tooth- and patient-related factors and tooth loss during supportive periodontal care (SPC). MATERIALS AND METHODS: A prospective observational study was carried out on previously treated periodontitis patients followed up for 5 years in SPC. The risk profile (low, moderate, high) of each patient based on periodontal risk assessment (PRA) scoring at baseline was evaluated, and tooth loss rates were analysed. RESULTS: Two hundred patients were included in the study, and 143 had 5-year follow-up data available for analysis. The overall annual tooth loss per patient was 0.07 ± 0.14 teeth/patient/year. Older age, smoking, staging and grading were associated with increased tooth loss rates. Most patients whose teeth were extracted belonged to the PRA high-risk group. Both PRA and a tooth prognosis system used at baseline showed high negative predictive value but low positive predictive value for tooth loss during SPC. CONCLUSIONS: Overall, the tooth loss rate of periodontitis patients in this prospective cohort study under SPC in private practice was low. Both tooth-based and patient-based prognostic systems can identify high-risk cases, but their positive predictive value should be improved.

Minimally invasive non-surgical periodontal therapy of intrabony defects: A prospective multi-centre cohort study.

AIM: To assess the potential benefits of minimally invasive non-surgical therapy (MINST) in teeth with intrabony defects and to explore factors associated with the outcomes. MATERIALS AND METHODS: A multi-centre trial was conducted in 100 intrabony defects in periodontitis patients in private practice. Steps 1 and 2 periodontal therapy including MINST were provided. Clinical and radiographic data were analysed at baseline and 12 months after treatment, with the primary aim being change in radiographic defect depth at 12 months. RESULTS: Eighty-four patients completed the 12-month follow up. The mean total radiographic defect depth reduced by 1.42 mm and the defect angle increased by 3° (both p < .05). Statistically significant improvements in probing pocket depth (PPD) and clinical attachment level (CAL) were seen at 12 months compared to baseline (p < .001). Fifty-six defects (66.7%) achieved pocket closure (PPD ≤ 4 mm) and 49 defects (58.3%) achieved the composite outcome (PPD ≤ 4 mm and CAL gain ≥3 mm). Deeper and narrower angled defects were positively correlated with radiographic and clinical improvements, respectively. CONCLUSIONS: Improvements in clinical and radiographic outcomes were seen after MINST. This study highlights the generalizability and wide applicability of this approach, further supporting its effectiveness in the treatment of intrabony defects. CLINICAL TRIAL REGISTRATION: NCT03741374. https://clinicaltrials.gov/study/NCT03741374?cond=minimally%20invasive%20non%20surgical%20therapy&locStr=UK&country=United%20Kingdom&distance=50&rank=2.

Interdental papilla reconstruction: a systematic review.

OBJECTIVES: To assess treatment options for the reconstruction of the lost interdental papilla and to evaluate evidence for their efficacy. METHODS: An electronic search (Medline, Embase and the Cochrane Library Database and OpenGray) and a hand search were carried out to identify all types of studies investigating interdental papilla reconstruction (except for reviews) with a minimum of 3 months follow-up. RESULTS: Forty-five studies were included in the study including 7 RCTs, 2 cohort studies, 19 case series and 17 case reports. Fifteen studies reported on the use of hyaluronic acid, 6 studies on platelet-rich fibrin, 16 studies on soft tissue grafting, 4 studies on orthodontics and 4 on additional modalities. The most common outcome measures were black triangle dimensions and papillary fill percentage. Meta-analysis was not possible due to the high heterogeneity of the studies. CONCLUSION: There are various options for interdental papilla reconstruction of which hyaluronic acid injections, PRF, surgical grafting and orthodontics seem to improve outcomes at a minimum 3 months. The use of soft tissue grafting with sub-epithelial connective tissue graft seems to be associated with the most robust evidence for the longer-term reduction of 'black triangles'. There is insufficient evidence to make recommendations to clinicians. Further research is needed in the form of well conducted RCTs with longer follow ups and patient reported outcome measures. CLINICAL RELEVANCE: Patients frequently complain about the appearance of black triangles and their management options seem unclear. This systematic review provides insight into the available reconstructive options.

Repurposing Metformin for periodontal disease management as a form of oral-systemic preventive medicine.

BACKGROUND: Despite the improvements in treatment over the last decades, periodontal disease (PD) affects millions of people around the world and the only treatment available is based on controlling microbial load. Diabetes is known to increase the risk of PD establishment and progression, and recently, glucose metabolism modulation by pharmaceutical or dietarian means has been emphasised as a significant modulator of non-communicable disease development. METHODS: The impact of pharmaceutically controlling glucose metabolism in non-diabetic animals and humans (REBEC, UTN code: U1111-1276-1942) was investigated by repurposing Metformin, as a mean to manage periodontal disease and its associated systemic risk factors. RESULTS: We found that glucose metabolism control via use of Metformin aimed at PD management resulted in significant prevention of bone loss during induced periodontal disease and age-related bone loss in vivo. Metformin also influenced the bacterial species present in the oral environment and impacted the metabolic epithelial and stromal responses to bacterial dysbiosis at a single cell level. Systemically, Metformin controlled blood glucose levels and age-related weight gain when used long-term. Translationally, our pilot randomized control trial indicated that systemic Metformin was safe to use in non-diabetic patients and affected the periodontal tissues. During the medication window, patients showed stable levels of systemic blood glucose, lower circulating hsCRP and lower insulin levels after periodontal treatment when compared to placebo. Finally, patients treated with Metformin had improved periodontal parameters when compared to placebo treated patients. CONCLUSION: This is the first study to demonstrate that systemic interventions using Metformin in non-diabetic individuals aimed at PD prevention have oral-systemic effects constituting a possible novel form of preventive medicine for oral-systemic disease management.

Minimal invasiveness in nonsurgical periodontal therapy.

Periodontal treatment is quickly moving towards a philosophy consisting of a less invasive approach. In this context, minimally invasive nonsurgical therapy (MINST) is a promising option. This paper reviews the concepts behind minimal invasiveness in nonsurgical periodontology and reports the state-of the art evidence for this topic. Instruments used and protocols suggested for these applications are introduced and discussed. The original papers reviewed show probing pocket depth (PPD) reductions and clinical attachment level (CAL) gains ranging from 2 to 4 mm between baseline and 6 months to 5 years posttreatment for intrabony defects and from 1.5 to 3 mm between baseline and 2-6 months of follow-up for full-mouth results. These clinical outcomes are accompanied by statistically significant reductions in radiographic bone defect depth and increases in intrabony defect angles posttreatment. Wound healing mechanisms following MINST are presented, and clinical applications and directions for future research are suggested.

The association between Aggregatibacter actinomycetemcomitans JP2 clone and periodontitis: A systematic review and meta-analysis.

To appraise the literature on the prevalence of the JP2 clone of Aggregatibacter actinomycetemcomitans (A.a.) and on its association with presence and progression of periodontitis in different populations. A systematic search of the literature was conducted in Medline, Embase and Cochrane Library for studies reporting data on detection of the JP2 clone of A.a. A total of 56 papers were included in the review, from an initial search of 685 titles. Studies were carried out in populations with a mean age of 26.34 years (range 6.24-53.85 years). Just over 16% of the overall population assessed (n = 13 751) had the JP2 clone detected. Meta-analyses included 16 studies and 1775 patients, and revealed an association between detection of the JP2 clone and diagnosis of periodontitis (RR = 1.86, 95% 1.43-2.42) from saliva and plaque, with high heterogeneity (I2  = 85%, p < .00001). Meta-analyses included 5 studies and 616 patients, and revealed an association between baseline detection of the JP2 clone and onset of periodontitis over 2 to 5 years (RR = 4.12, 95% 2.42-7.00), with high heterogeneity (I2  = 81%, p < .0003). From the overall risk of bias score, 29 papers were judged as low risk of bias, whilst the remaining papers were judged to have an overall medium or high risk of bias. Detection of the JP2 clone of A.a. in subgingival plaque and saliva samples is associated with increased odds of diagnosis of periodontitis and may be able to predict onset of periodontitis. This systematic review provides clear evidence that in certain populations, the JP2 clone of A.a. is associated with early-onset periodontitis. Furthermore, detection of this bacterium seems to be predictive of disease onset.

Association between defect morphology and healing of intrabony defects treated with minimally invasive non-surgical therapy: A pilot exploratory analysis of two cohorts.

OBJECTIVE: The aim of this study was to explore the associations between defect morphology (defined by clinical and radiographic parameters) and the healing of periodontal intrabony defects treated with minimally invasive non-surgical therapy (MINST). BACKGROUND DATA: MINST has shown to result in favorable clinical and radiographic improvements in intrabony defects. However, it is not clear which types of intrabony defects are most suitable for this treatment. METHODS: Clinical and radiographic analyses were carried out in a total of 71 intrabony defects treated with MINST belonging to two previously published studies. Baseline defect characteristics were analyzed and related to clinical and radiographic outcomes at 12 months post-MINST with or without adjunctive enamel matrix derivative. RESULTS: No associations were detected between defect depth, angle and predicted number of walls and clinical and radiographic healing 12 months post-MINST. CONCLUSIONS: No evidence emerged for associations between defect characteristics and healing following MINST. These data seem to suggest that factors other than defect morphology may influence treatment response to MINST.

Metabolomics analysis in saliva from periodontally healthy, gingivitis and periodontitis patients.

OBJECTIVE: The aim of this study was to investigate metabolomics markers in the saliva of patients with periodontal health, gingivitis and periodontitis. BACKGROUND: The use of metabolomics for diagnosing and monitoring periodontitis is promising. Although several metabolites have been reported to be altered by inflammation, few studies have examined metabolomics in saliva collected from patients with different periodontal phenotypes. METHODS: Saliva samples collected from a total of 63 patients were analysed by nuclear magnetic resonance (NMR) followed by ELISA for interleukin (IL)-1ß. The patient sample, well-characterised clinically, included periodontal health (n = 8), gingivitis (n = 19) and periodontitis (n = 36) cases, all non-smokers and not diabetic. RESULTS: Periodontal diagnosis (healthy/gingivitis/periodontitis) was not associated with any salivary metabolites in this exploratory study. Periodontal staging showed nominal associations with acetoin (p = .030) and citrulline (p = .047). Among other investigated variables, the use of systemic antibiotics in the previous 3 months was associated with higher values of the amino acids taurine, glycine and ornithine (p = .002, p = .05 and p = .005, respectively, at linear regression adjusted for age, gender, ethnicity, body mass index and staging). CONCLUSION: While periodontal staging was marginally associated with some salivary metabolites, other factors such as systemic antibiotic use may have a much more profound effect on the microbial metabolites in saliva. Metabolomics in periodontal disease is still an underresearched area that requires further observational studies on large cohorts of patients, aiming to obtain data to be used for clinical translation.

Molecular profiling of gingival crevicular fluid fails to distinguish between infrabony and suprabony periodontal defects.

AIM: To assess the differential molecular profiling of gingival crevicular fluid (GCF) from infrabony and suprabony periodontal defects compared with healthy sites. MATERIALS AND METHODS: Seventy-five samples from 25 patients with untreated periodontitis stage III-IV were included. Clinical and radiological parameters as well as GCF samples were collected from an infrabony defect, a suprabony defect and a periodontally healthy site per patient. A multiplex bead immunoassay was performed to assess the level of 18 biomarkers associated with inflammation, connective tissue degradation and regeneration/repair. RESULTS: GCF volume was higher in periodontal sites compared with healthy sites, with no significant difference between infrabony and suprabony defects. Fourteen biomarkers were elevated in infrabony and suprabony sites compared with healthy sites (p < .05). Only interleukin-1α levels were increased in infrabony compared with suprabony sites, whereas there was no difference in probing pocket depth. CONCLUSIONS: Although the GCF molecular profile clearly differentiates periodontally affected sites from healthy sites, the different architecture between infrabony and suprabony defects is not reflected in GCF biomarker changes.

The efficacy of bone reconstructive therapies in the management of peri-implantitis. A systematic review and meta-analysis.

AIM: To evaluate the efficacy of bone reconstructive procedures for the reduction of probing pocket depth (PPD), bleeding on probing (BOP), and suppuration in peri-implantitis-related bone defects at ≥12-month follow-up. MATERIALS AND METHODS: Three databases were searched for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared bone reconstructive therapies to access flap surgery (AFS) (Focused Question-FQ 1), and RCTs, CCTs, and prospective case series that assessed the efficacy of reconstructive therapies (FQ 2). Meta-analysis was performed for FQ1 when more than three studies were identified, while for FQ2 a network was drawn based on RCTs with common treatment arms. RESULTS: Seven RCTs were identified for FQ1 while five RCTs and six prospective case series for FQ2. There was no significant difference in PPD change between AFS and reconstructive surgery (-0.387; p = .325) at 12 months. Furthermore, no clear differences in terms of PPD and BOP changes resulted from the different reconstructive therapies included in the network. Only a small percentage of treated cases with any modality achieved peri-implantitis resolution, as defined by different composite outcomes. CONCLUSIONS: Reconstructive surgery does not offer significant improvements in peri-implant clinical parameters as compared to AFS at 12 months. It was not possible to establish a hierarchy of efficacy among the different biomaterials employed for reconstructive surgery.

Development and international validation of logistic regression and machine-learning models for the prediction of 10-year molar loss.

AIM: To develop and validate models based on logistic regression and artificial intelligence for prognostic prediction of molar survival in periodontally affected patients. MATERIALS AND METHODS: Clinical and radiographic data from four different centres across four continents (two in Europe, one in the United States, and one in China) including 515 patients and 3157 molars were collected and used to train and test different types of machine-learning algorithms for their prognostic ability of molar loss over 10 years. The following models were trained: logistic regression, support vector machine, K-nearest neighbours, decision tree, random forest, artificial neural network, gradient boosting, and naive Bayes. In addition, different models were aggregated by means of the ensembled stacking method. The primary outcome of the study was related to the prediction of overall molar loss (MLO) in patients after active periodontal treatment. RESULTS: The general performance in the external validation settings (aggregating three cohorts) revealed that the ensembled model, which combined neural network and logistic regression, showed the best performance among the different models for the prediction of MLO with an area under the curve (AUC) = 0.726. The neural network model showed the best AUC of 0.724 for the prediction of periodontitis-related molar loss. In addition, the ensembled model showed the best calibration performance. CONCLUSIONS: Through a multi-centre collaboration, both prognostic models for the prediction of molar loss were developed and externally validated. The ensembled model showed the best performance in terms of both discrimination and validation, and it is made freely available to clinicians for widespread use in clinical practice.

Biomarkers for diagnosis of stage III, grade C with molar incisor pattern periodontitis in children and young adults: a systematic review and meta-analysis.

AIM: To explore the existing salivary, gingival crevicular fluid (GCF), blood, and serum biomarkers associated with grade C molar-incisor pattern (C/MIP) periodontitis in systemically healthy children and young adults. MATERIALS AND METHODS: Cross-sectional, case-control, and cohort studies on stage III grade C periodontitis or former equivalent diagnosis with analysis of molecular biomarkers in saliva, GCF, blood, or serum were retrieved from six databases and screened based on the eligibility criteria. The risk of bias in included studies was evaluated. Meta-analysis was planned for biomarkers assessed using the same detection methods and sample type in at least two papers. RESULTS: Out of 5621 studies identified at initial screening, 28 papers were included in the qualitative analysis of which 2 were eligible for meta-analysis for IgG in serum samples. Eighty-seven biomarkers were assessed with the majority being higher in cases than in controls. Only the meta-analysis of total serum IgG with low heterogeneity value revealed a significant increase in its levels in C/MIPs compared to controls (standardised mean difference: 1.08; 95% CI: 0.76, 1.40). CONCLUSION: There is a paucity of data on biomarkers associated with molar-incisor pattern periodontitis. Although serum IgG levels are raised, other more specific biomarkers in saliva, GCF, and blood/serum may be promising but require further investigation.

Could dietary restrictions affect periodontal disease? A systematic review.

OBJECTIVE: This review aimed at evaluating the possible benefits that caloric restriction (CR) may provide to periodontal disease progression and response to treatment. MATERIAL AND METHODS: Electronic search on Medline, Embase and Cochrane, and manual search were performed to identify pre-clinical and on human studies reporting the consequences of CR on clinical and inflammatory parameters related to periodontitis. Newcastle Ottawa System and SYRCLE scale were used to assess the risk of bias. RESULTS: Four thousand nine hundred eighty articles were initially screened, and a total of 6 articles were finally included, consisting of 4 animal studies and 2 studies in humans. Due to the limited number of studies and heterogeneity of the data, results were presented in descriptive analyses. All studies showed that, compared to the normal (ad libitum) diet, CR might have the potential to reduce the local and systemic hyper-inflammatory state as well as disease progression in periodontal patients. CONCLUSIONS: Within the existing limitations, this review highlights that CR showed some improvements in the periodontal condition by reducing the local and systemic inflammation related to the periodontitis and by improving clinical parameters. However, the results should be interpreted with caution since robust research such as randomized clinical trials is still missing. CLINICAL RELEVANCE: This review shows that some dietary/caloric restrictions approaches may have the potential to improve periodontal conditions and, in addition, highlights a need for human studies with a robust methodology in order to draw stronger evidence-based conclusions.

Association between periodontal diseases and COVID-19 infection: a case-control study with a longitudinal arm.

Some studies have suggested potential relationships between periodontal disease and COVID-19, explained by many possible pathological pathways. The aim of this case-control study with a longitudinal arm was to investigate this association. 80 systemically healthy individuals (apart from COVID-19) were involved in this study, divided into 40 patients who had recently had COVID-19 (test, divided into severe and mild/moderate cases) and 40 who had not had COVID-19 (control). Clinical periodontal parameters and laboratory data were recorded. Mann-Whitney U test, Wilcoxon test, and chi-square test were performed to compare variables. Multiple binary logistic regression method was used to estimate adjusted ORs and 95% confidence interval. Hs-CRP-1 and 2, Ferritin-1 and 2, lymphocyte count-1 values, and neutrophil/lymphocyte ratio-1 were higher in patients with severe COVID-19 than patients with mild/moderate COVID-19 (p < 0.05). All of these laboratory values significantly decreased after COVID-19 treatment (p < 0.05) in the test group. Presence of periodontitis (p = 0.015) was higher and periodontal health was lower (p = 0.002) in the test group than in the control group. All clinical periodontal parameters were significantly higher in the test group than in the control group (p < 0.05), except plaque index. Prevalence of periodontitis was associated with increased odds of having COVID-19 infection (PR = 1.34; 95% CI 0.23-2.45) in the multiple binary logistic regression. COVID-19 is associated with periodontitis prevalence, through a series of possible mechanisms including local and systemic inflammatory responses. Further studies should investigate whether the maintenance of periodontal health may be a factor in the reduction of the severity of COVID-19 infections.

Associations between Host Genetic Variants and Subgingival Microbiota in Patients with the Metabolic Syndrome.

Host genetic variants may affect oral biofilms, playing a role in the periodontitis-systemic disease axis. This is the first study to assess the associations between host genetic variants and subgingival microbiota in patients with metabolic syndrome (MetS); 103 patients with MetS underwent medical and periodontal examinations and had blood and subgingival plaque samples taken. DNA was extracted and processed, assessing a panel of selected single nucleotide polymorphisms (SNPs) first (hypothesis testing) and then expanding to a discovery phase. The subgingival plaque microbiome from these patients was profiled. Analysis of associations between host genetic and microbial factors was performed and stratified for periodontal diagnosis. Specific SNPs within RUNX2, CAMTA1 and VDR genes were associated with diversity metrics with no genome-wide associations detected for periodontitis severity or Mets components at p < 10-7. Severe periodontitis was associated with pathogenic genera and species. Some SNPs correlated with specific bacterial genera as well as with microbial taxa, notably VDR (rs12717991) with Streptococcus mutans and RUNX2 (rs3749863) with Porphyromonas gingivalis. In conclusion, variation in host genotypes may play a role in the dysregulated immune responses characterizing periodontitis and thus the oral microbiome, suggesting that systemic health-associated host traits further interact with oral health and the microbiome.

Periodontitis and implant complications in diabetes.

Epidemiologic evidence indicates that periodontitis is more frequent in patients with uncontrolled diabetes mellitus than in healthy controls, suggesting that it could be considered the "sixth complication" of diabetes. Actually, diabetes mellitus and periodontitis are two extraordinarily prevalent chronic diseases that share a number of comorbidities all converging toward an increased risk of cardiovascular disease. Periodontal treatment has recently been shown to have the potential to improve the metabolic control of diabetes, although long-term studies are lacking. Uncontrolled diabetes also seems to affect the response to periodontal treatment, as well as the risk to develop peri-implant diseases. Mechanisms of associations between diabetes mellitus and periodontal disease include the release of advanced glycation end products as a result of hyperglycemia and a range of shared predisposing factors of genetic, microbial, and lifestyle nature. This review discusses the evidence for the risk of periodontal and peri-implant disease in diabetic patients and the potential role of the dental professional in the diabetes-periodontal interface.

Molecular profiling of intrabony defects' gingival crevicular fluid.

AIM: To profile, for the first time, the gingival crevicular fluid (GCF) of intrabony defects against a wide array of inflammatory and regenerative markers. MATERIALS AND METHODS: Twenty-one patients contributed one intrabony defect and one periodontally healthy site. Clinical and radiographic measures were obtained. GCF samples were analyzed with multiplex bead immunoassays over 27 markers previously identified by our group. Comparisons were performed using Wilcoxon matched-pairs signed-ranks tests, using a Bonferroni corrected α = 0.05/27 = 0.0019. RESULTS: Intrabony defect sites presented significantly increased GCF volume and disease-associated clinical and radiographic characteristics (p < .05). Intrabony defect sites presented significantly increased IL-1α, IL-1ß, IL-6, IFN-γ, and MMP-8 levels compared with periodontally healthy sites (p < .0019). For regeneration markers, significantly higher FGF basic and VEGF levels were observed (p < .0019). Notably, traits of cell senescence were identified for the first time in the GCF. CONCLUSIONS: The differentiation of intrabony defects from periodontally healthy control sites can be based on clinical and radiographic measures and on a differentiated GCF profile that is site-specific. Alongside catabolic processes, through significant up-regulation of inflammation and connective tissue remodeling, unique molecular characteristics of intrabony defects may render them a microenvironment amenable to regeneration. Traits of the senescence-associated secretory phenotype may suggest the existence of senescent cells during periodontal inflammation in intrabony defects.

Expression of periodontitis susceptibility genes in human gingiva using single-cell RNA sequencing.

OBJECTIVE: Single-cell transcriptomics was used to determine the possible cell-type specificity of periodontitis susceptibility genes. BACKGROUND: The last decade has witnessed remarkable advances in the field of human genomics. Despite many advances, the genetic factors associated with or contributing to the periodontitis pathogenesis have only been identified to a limited extent and are often poorly validated. Confirming whether a given single nucleotide polymorphism has an association with periodontitis requires a robust mechanistic explanation on the functional consequences of a given genetic variant. METHODS: We globally assessed the expression of 26 disease-associated genes identified by GWAS within the gingival mucosa. A total of 12 411 cells from 4 different donors were analysed. Differentially expressed genes were analysed using Seurat, a non-parametric Wilcoxon rank sum test. The minimum threshold for significance was defined as p < .05. RESULTS: This exploration at a cellular-level suggests diverse populations contributing to disease pathogenesis, with macrophages expressing a higher number of the analysed disease-associated genes. IL1B, PTGS2, FCGR2A, IL10 and IL1A specifically showed a more restricted expression in the myeloid lineages. CONCLUSION: This short report combines human genetics and single-cell genomics to better understand periodontitis by mapping variants to predict their cells of action and putative functions. These findings seem to suggest that innate cell dysfunction is linked to disease susceptibility.