Oral biopsy in mucous membrane pemphigoid and pemphigus vulgaris with gingival expression: the optimal site. A systematic review and meta-analysis.

PURPOSE: In order to diagnose mucous membrane pemphigoid (MMP) and pemphigus vulgaris (PV) with gingival expression, clinical data must be compared with immunohistochemical data obtained using direct immunofluorescence (DIF). It is therefore essential to carry out a good quality mucosal biopsy for this vital additional test. To date, no study has been able to effectively guide clinicians in their choice of oral site for biopsy to guarantee the efficient contribution of DIF to diagnosis. We propose a systematic review of the literature and a meta-analysis to clarify this issue. MATERIALS AND METHODS: Electronic databases and bibliographies of articles were searched in April 2023. The primary outcome was the rate of DIF + contribution to diagnosis according to the location of the oral site biopsied. RESULTS: 16 studies were included. Gingival biopsies showed a rate of DIF + 100% [97%-100%] p = 0.998 I2 = 0.0% with no heterogeneity for PV, and 90.2% [66.5%-100%] p < 0.001 I2 = 89.6% with high heterogeneity for MMP. For the other oral sites, this rate was 95.7% [87.4%- 100%] p = 0.011 I2 = 73.0% with moderate heterogeneity for PV, and 87.4% [70.1%- 98.7%] p < 0.001 I2 = 92.6% with high heterogeneity for MMP. In addition, meta-regression confirmed the significant association between the appearance of the biopsied mucosa and the rate of DIF + in MMP (p < 0.001), with no influence on residual heterogeneity. CONCLUSION: The nature of the oral mucosa biopsied does not influence the rate of DIF + to diagnosis. The choice of biopsy site should only take into account the characteristics of the clinical picture and the benefit/risk balance of the surgical protocol. The sample must be taken in healthy aeras as close as possible of active lesions: on the gingiva if the MMP and PV are strictly gingival, on the alveolar mucosa if the whole gingiva is altered and on any healthy mucosa if a large number of oral sites are affected. CLINICAL TRIALS: CRD42023392345.

Giant peripheral ossifying fibroma of gingiva: a diagnostic workup.

Reactive lesions of the oral cavity are non-neoplastic proliferations occurring due to chronic irritation. Peripheral ossifying fibroma (POF) is a reactive lesion usually occurring on the interdental papilla. POF is predominantly found in the second decade of life with a definitive female predilection. This is a case report of a middle-aged male patient with gingival overgrowth in left lower back tooth region. Clinically, the lesion was asymptomatic, firm, pale pink and sessile but unusually large in size. Surgical excision of the lesion was done followed by histopathological confirmation with emphasis on the diagnosis. The case in question is interesting because of its large size and location.

Preclinical evaluation of mucogingival defect treatment using piscine membranes: An in vivo assessment of wound healing.

Periodontitis is a bacteria-induced chronic inflammatory disease characterized by degradation of the supporting tissue and bone in the oral cavity. Treatment modalities seek to facilitate periodontal rehabilitation while simultaneously preventing further gingival tissue recession and potentially bone atrophy. The aim of this study was to compare two differently sourced membranes, a resorbable piscine collagen membrane and a porcine-derived collagen membrane, in the repair of soft tissue defects utilizing a preclinical canine model. This in vivo component consisted of 10 beagles which were subjected to bilateral maxillary canine mucogingival flap defects, as well as bilateral soft tissue defects (or pouches) with no periodontal ligament damage in the mandibular canines. Defects received either a piscine-derived dermal membrane, (Kerecis® Oral, Ísafjörður, Iceland) or porcine-derived dermal membrane (Geistlich Mucograft®, Wolhusen, Switzerland) in a randomized fashion (to avoid site bias) and were allowed to heal for 30, 60, or 90 days. Statistical evaluation of tissue thickness was performed using general linear mixed model analysis of variance and least significant difference (LSD) post hoc analyses with fixed factors of time and membrane. Semi-quantitative analysis employed for inflammation assessment was evaluated using a chi-squared test along with a heteroscedastic t-test and values were reported as mean and corresponding 95% confidence intervals. In both the mucogingival flap defects and soft tissue gingival pouches, no appreciable qualitative differences were observed in tissue healing between the membranes. Furthermore, no statistical differences were observed in the thickness measurements between piscine- and porcine-derived membranes in the mucogingival flap defects (1.05 mm [±0.17] and 1.29 mm [±0.17], respectively [p = .06]) or soft tissue pouches (1.36 mm [±0.14] and 1.47 mm [±0.14], respectively [p = .27]), collapsed over time. Independent of membrane source (i.e., piscine or porcine), similar inflammatory responses were observed in both the maxilla and mandible at the three time points (p = .88 and p = .79, respectively). Histologic and histomorphometric evaluation results indicated that both membranes yielded equivalent tissue responses, remodeling dynamics and healing patterns for the mucogingival flap as well as the soft tissue gingival pouch defect models.

Influence of gingival phenotype on crestal bone loss at implants : A long-term 2 to 20-year cohort study in periodontally compromised patient.

PURPOSE: The aim of this long-term cohort study in periodontally compromised patients with implants was to analyze the correlation between gingival phenotype and peri-implant crestal bone loss, and between clinical measures and gingival phenotype. METHODS: Implant-supported single crowns and bridges were used to rehabilitate 162 implants in 57 patients. Patients were examined over a 2 to 20-year period on a recall schedule of 3 to 6 months. In addition to recording clinical parameters, intraoral radiographs were taken at baseline (immediately after superstructure insertion) and at 1, 3, 5, 10, 15, and 20 years. Patients were differentiated into phenotype 1 with thin, scalloped gingiva and narrow attached gingiva (n = 19), phenotype 2 with thick, flat gingiva and wide attached gingiva (n = 23), or phenotyp 3 with thick, scalloped gingiva and narrow attached gingiva (n = 15). RESULTS: The mean peri-implant crestal bone loss during the first 12 months was 1.3 ± 0.7 mm. Patients with gingival phenotype 1 had a significantly greater rate of increased crestal bone loss at implants (p = 0.016). No significant differences were present in subsequent years. The prevalence of mucositis at all implants was 27.2%, and the prevalence of peri-implantitis 9.3%. Univariate analyses indicated a significantly higher peri-implantitis risk in patients with gingival phenotype 2 (p-OR = 0.001; p-OR = 0.020). The implants of patients with phenotype 2 had significantly greater probing depths (1st year p < 0.001; 3rd year p = 0.016; 10th year p = 0.027; 15th year p < 0.001). Patients with gingival phenotype 3 showed no significantly increased probing depths, signs of inflammation and crestal bone loss. CONCLUSIONS: Patients with a gingival phenotype 1 have greater crestal bone loss at implants during the first year of functional loading. Patients with gingival phenotype 2 had significantly greater probing depth at implants and risk of peri-implantitis.

A preliminary investigation into the impact of soft tissue augmentation-based periodontal phenotype modification therapy for patients exhibiting class III decompensation.

BACKGROUND: Patients with skeletal angle Class III malocclusion usually have inadequate hard and soft tissue volume at the mandibular anterior teeth. The labial proclination at the teeth may lead to gingival recession. The purpose of this study was to explore whether periodontal phenotype modification therapy with soft tissue augmentation (PhMT-s) can prevent gingival recession in these patients. METHODS: Four patients with skeletal Class III malocclusion and a thin periodontal phenotype underwent surgical-orthodontic treatment. Prior to tooth movement, they underwent a minimally invasive vestibular incision with subperiosteal tunnel access combined with autogenous connective tissue grafts for periodontal phenotype modification with soft tissue augmentation (PhMT-s). The labial gingival thickness of the anterior mandibular teeth was measured at three distinct levels: at the cementoenamel junction (GT0), 3 mm apical to the CEJ (GT3), and 6 mm apical to the CEJ (GT6). These measurements were taken at baseline, three months following PhMT-s, and after tooth decompensation. Additionally, a biopsy sample was obtained from the PhMT-s site of one patient. All sections were subsequently stained using hematoxylin and eosin, Masson trichrome, Sirius Red, and immunohistochemistry. RESULTS: The thickness of the labial gingiva was increased about 0.42 to 2.00 mm after PhMT-s. At the end of pre-orthognathic surgical orthodontic treatment, the thickness of the labial gingiva was increased about - 0.14 to 1.32 mm compared to the baseline and no gingival recession occurred after the pre-orthognathic surgical orthodontic treatment. The histologic results demonstrated that the grafts obtained from the PhMT-s site exhibited increased deposition of collagen fibers. Moreover, the proportion of type III collagen increased and the grafts displayed significantly reduced positive expression of CD31 and OCN. CONCLUSIONS: PhMT-s increased the thickness of the soft tissue, stabilizing the gingival margin for teeth exhibiting a thin periodontal phenotype and undergoing labial movement. This is attributed to the increased deposition of collagen fibers.

Deep learning based approach: automated gingival inflammation grading model using gingival removal strategy.

Gingival inflammation grade serves as a well-established index in periodontitis. The aim of this study was to develop a deep learning network utilizing a novel feature extraction method for the automatic assessment of gingival inflammation. T-distributed Stochastic Neighbor Embedding (t-SNE) was utilized for dimensionality reduction. A convolutional neural network (CNN) model based on DenseNet was developed for the identification and evaluation of gingival inflammation. To enhance the performance of the deep learning (DL) model, a novel teeth removal algorithm was implemented. Additionally, a Grad-CAM + + encoder was applied to generate heatmaps for computer visual attention analysis. The mean Intersection over Union (MIoU) for the identification of gingivitis was 0.727 ± 0.117. The accuracy rates for the five inflammatory degrees were 77.09%, 77.25%, 74.38%, 73.68% and 79.22%. The Area Under the Receiver Operating Characteristic (AUROC) values were 0.83, 0.80, 0.81, 0.81 and 0.84, respectively. The attention ratio towards gingival tissue increased from 37.73% to 62.20%, and within 8 mm of the gingival margin, it rose from 21.11% to 38.23%. On the gingiva, the overall attention ratio increased from 51.82% to 78.21%. The proposed DL model with novel feature extraction method provides high accuracy and sensitivity for identifying and grading gingival inflammation.

Interplay of co-cultured chimeric adipose and gingival tissues exacerbates inflammatory dysfunction relevant to periodontal and metabolic conditions.

Adipose tissue dysfunction is a key feature of metabolic syndrome, which increases the risk of periodontitis, an inflammatory disease induced by bacteria that affects the gingiva and other components of periodontal tissue. Recent studies indicate that molecules from inflamed periodontal tissue contribute to adipose tissue dysfunction. However, the cellular mechanisms and interactions between adipose tissue and gingiva driving the progression of metabolic and periodontal conditions remain unclear. To address this, we developed a chimeric (mouse/human) co-culture tissue model (which identifies the origins of species-specific cytokines) to investigate these interactions. Using tissue-specific functional cells and immunocytes, we constructed equivalents of adipose tissue (ATE) and gingiva (GTE), co-cultivating them under inflammatory conditions induced by bacterial endotoxin, lipopolysaccharide (LPS). Our findings showed that exposure to LPS resulted in a notable reduction in lipid accumulation, GLUT4 expression, and adiponectin secretion in ATE, along with increased macrophage colonies forming around lipid droplets, as well as elevated levels of triglyceride, leptin, and IL-6. In GTE, LPS triggered significant inflammatory responses, characterized by increased macrophage accumulation, elevated COX-2 expression, and heightened secretion of inflammatory cytokines. LPS also reduced epithelial thickness and the expression of keratin 19 and collagen IV, indicating impaired barrier function and gingival integrity. Co-culturing ATE with GTE exacerbated these LPS-induced harmful effects in both tissues. In conclusion, our findings suggest that interplay between gingiva and adipose tissue can intensify the inflammatory and dysfunctional changes caused by LPS. This co-culture tissue model offers a valuable tool for future studies on periodontitis and metabolic syndrome.

Gingival open-wound to increase keratinized tissue in implant rehabilitation-A technical note.

Keratinized tissue augmentation around implants guarantees long-term success and maintenance of implant rehabilitations. Free gingival grafting is often described as the gold standard, especially when dealing with limited residual keratinized tissue height. Traditionally, an epithelio-conjunctive graft is harvested, either on the palate or the tuberosity, to reconstruct the missing keratinized soft tissues. This article introduces an innovative approach to increase keratinized tissue around implants, benefiting from second-intention gingival healing. This original surgical approach is interesting because it does not involve autogenous grafting or biomaterials. Its main goals are to enhance predictability while reducing the numerous per and post-operative risks related to autogenous harvesting. The success of this technique depends on the observance of fundamental principles: protection against bacterial contamination (immunocompetence of the patient), phenotypic induction (preoperative presence of keratinized tissue), space maintenance, and stabilization of flaps.

Digital three-dimensional assessment of free gingival graft remodeling over 12 months.

OBJECTIVE: To digitally evaluate the three-dimensional (3D) remodelling of FGG used to treat RT2 gingival recessions and lack of keratinized tissue on mandibular incisor teeth. METHODS: Data from 45 patients included in a previous multicentric RCT were analyzed. Silicone impressions were taken before (baseline) and 3, 6 and 12 months after standardized FGG placement. Casts were scanned and images were superimposed, using digital software, to obtain measurements of estimated soft tissue thickness (eTT; 1, 3, and 5 mm apical to baseline gingival margin). In addition, soft tissue volume (STV) and creeping attachment (CA) were assessed. RESULTS: All patients exhibited postoperative eTT and STV increases, at all time points. The greatest mean thickness gain was observed at eTT3 (1.0 ± 0.4 mm) at 12 months. At 12 months, STV was 52.3 ± 21.1 mm3, without relevant changes compared to the 3- and 6-month follow-up. CA, which was observed as early as six months postoperatively, was evident in ∼85 % of teeth at 12 months. CONCLUSIONS: Application of FGG was an effective phenotype modification therapy, as shown by the significantly increased tissue thickness postoperatively. Despite the use of FGG technique not aiming for root coverage, digital 3D assessment documented the early and frequent postoperative occurrence of CA, which helped improve recession treatment outcomes. CLINICAL SIGNIFICANCE: The use of 3D assessment methodology allows precise identification of the tissue gain obtained with FGG, which, regardless of technique, results in predictable phenotype modification and frequent occurrence of creeping attachment.

Influence of mucosal tissue height on implant crestal bone: A 10-year follow-up of a controlled clinical trial.

OBJECTIVE: To evaluate the 10-year influence of soft tissue height (STH) on crestal bone level changes (CBC) in bone-level implants with non-matching internal conical connections. MATERIAL & METHODS: From the initial 97 patients, 59 (19 men, 40 women, age 55.86 ± 9.5 years) returned for the recall visit. Based on baseline STH, they were categorized into T1 (thin STH ≤2 mm, n = 33), T2 (thin STH augmented with allogenic tissue matrix (ATM), n = 32), and C (thick STH >2 mm, n = 32). Implants were placed in the posterior mandible using a one-stage approach and received single screw-retained restorations. Clinical (PPD, BOP, PI) and radiographic examinations were conducted after 10 years, with CBC calculated mesial and distal to each implant. RESULTS: After 10 years, implants in surgically thickened (T2) or naturally thick STH (C) showed bone gains of 0.57 ± 0.55 mm and 0.56 ± 0.40 mm, respectively (p < 0.0001) shifting from an initial CBC of -0.21 ± 0.33 mm to 0.36 ± 0.29 mm in the thick STH group and -0.2 ± 0.35 mm to 0.37 ± 0.29 mm in the surgically thickened STH group. Implants in naturally thin STH yielded a non-significant trend of bone loss (-0.12 ± 0.41 mm; p > 0.05). CONCLUSIONS: Implants in thin STH (≤2 mm) exhibited greater CBC over the study period. Significant bone gains were observed in thick STH cases, indicating that naturally thick STH or STH augmentation with ATM may contribute to maintain CBC in long-term around implants. CLINICAL SIGNIFICANCE: This is the first long-term follow-up study suggesting that adequate soft tissue height around implants helps maintain stable peri­implant bone levels. While tissue thickness plays a key role, other factors also interact with peri­implant tissue height to sustain crestal bone stability over time.

Alveolar Ridge Preservation With Fibro-Gide or Connective Tissue Graft: A Randomized Controlled Trial of Soft and Hard Tissue Changes.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of a novel biomaterial (FG) for alveolar ridge preservation compared to CTG in terms of soft tissue thickness and bone dimensional changes. MATERIALS AND METHODS: A randomized clinical trial was conducted on 30 patients who required extraction of 30 hopeless mandibular posterior teeth. All patients went through atraumatic tooth extraction, and then, they were randomly allocated to either a CTG, an FG, or a spontaneous healing (SH) group (1:1:1). All patients received a dental implant placed 6 months postoperatively. The soft tissue thickness and bone dimensional changes were measured before and 6 months after the procedure. RESULTS: The study's analysis revealed statistically significant differences in buccal gingival thickness and dimensional bone changes across the three examined groups after 6 months (p < 0.05). The SH group had lower gingival thickness (1.31 ± 0.65 mm) and higher vertical resorption (-1.46 ± 1.67 mm at the buccal aspect) compared with the CTG and FG groups. The CTG and FG groups had similar gingival thickness (2.42 ± 0.70 and 3.00 ± 0.71 mm, respectively) and bone width reduction (+0.86 ± 2.31 and +0.93 ± 2.38 mm, respectively), whereas the CTG group had lower vertical bone loss (-0.30 ± 1.09 mm at the buccal aspect) than the FG group (-0.47 ± 2.30 mm at the buccal aspect). CONCLUSION: FG and CTG demonstrate equivalent soft tissue thickness and comparable horizontal bone dimension outcomes in ARP.

Changing behind the scenes.

Th17 cell plasticity is associated with pathogenicity in chronic inflammation. In a model of periodontitis, McClure et al. (https://doi.org/10.1084/jem.20232015) describe location-dependent divergence in Th17 plasticity, with surprisingly limited conversion in inflamed gingiva but emergence of protective exTh17-TfH cells in draining LN that enhance protective antibody.

Xenogeneic Collagen Matrix Versus Free Gingival Graft for Augmenting Peri-Implant Keratinized Mucosa Around Dental Implants: A Systematic Review and Meta-Analysis.

OBJECTIVES: There is a growing evidence to suggest augmenting peri-implant keratinized mucosa in the presence of ≤ 2 mm of keratinized mucosa. However, the most appropriate surgical technique and augmentation materials have yet to be defined. The aim of this systematic review and meta-analyses was to evaluate the clinical and patient-reported outcomes of augmenting keratinized mucosa around implants using free gingival graft (FGG) versus xenogeneic collagen matrix (XCM) before commencing prosthetic implant treatment. MATERIAL AND METHODS: Electronic databases were searched to identify observational studies comparing implant sites augmented with FGG to those augmented with XCM. The risk of bias was assessed using the Cochrane Collaboration's Risk of Bias tool. RESULTS: Six studies with 174 participants were included in the present review. Of these, 87 participants had FGG, whereas the remaining participants had XCM. At 6 months, sites augmented with FGG were associated with less changes in the gained width of peri-implant keratinized mucosa compared to those augmented with XCM (mean difference 1.06; 95% confidence interval -0.01 to 2.13; p = 0.05). The difference, however, was marginally significant. The difference between the two groups in changes in thickness of peri-implant keratinized mucosa at 6 months was statistically significantly in favor of FGG. On the other hand, XCM had significantly shorter surgical time, lower postoperative pain score, and higher color match compared to FGG. CONCLUSIONS: Within the limitation of this review, the augmentation of keratinized mucosa using FGG before the placement of the final prosthesis may have short-term positive effects on soft tissue thickness. XCM might be considered in aesthetically demanding implant sites and where patient comfort or shorter surgical time is a priority. The evidence support, however, is of low to moderate certainty; therefore, further studies are needed to support the findings of the present review.

Lysosomal dysfunction-derived autophagy impairment of gingival epithelial cells in diabetes-associated periodontitis with altered protein acetylation.

Diabetes-associated periodontitis (DP) presents severe inflammation and resistance to periodontal conventional treatment, presenting a significant challenge in clinical management. In this study, we investigated the underlying mechanism driving the hyperinflammatory response in gingival epithelial cells (GECs) of DP patients. Our findings indicate that lysosomal dysfunction under high glucose conditions leads to the blockage of autophagy flux, exacerbating inflammatory response in GECs. Single-cell RNA sequencing and immunohistochemistry analyses of clinical gingival epithelia revealed dysregulation in the lysosome pathway characterized by reduced levels of lysosome-associated membrane glycoprotein 2 (LAMP2) and V-type proton ATPase 16 kDa proteolipid subunit c (ATP6V0C) in subjects with DP. In vitro stimulation of human gingival epithelial cells (HGECs) with a hyperglycemic microenvironment showed elevated release of proinflammatory cytokines, compromised lysosomal acidity and blocked autophagy. Moreover, HGECs with deficiency in ATP6V0C demonstrated impaired autophagy and heightened inflammatory response, mirroring the effects of high glucose stimulation. Proteomic analysis of acetylation modifications identified altered acetylation levels in 28 autophagy-lysosome pathway-related proteins and 37 sites in HGECs subjected to high glucose stimulation or siATP6V0C. Overall, our finding highlights the pivotal role of lysosome impairment in autophagy obstruction in DP and suggests a potential impact of altered acetylation of relevant proteins on the interplay between lysosome dysfunction and autophagy blockage. These insights may pave the way for the development of effective therapeutic strategies against DP.

Reduction of osteoclast formation and survival following suppression of cytokines by diacerein in periodontitis.

Periodontitis causes an increase in several bioactive agents such as interleukins (IL), tumor necrosis factor (TNF)-α and receptor activator of NF-kB ligand (RANKL), which induce the osteoclast formation and activity. Since diacerein exerts anti-TNF-α and anti-IL-1 effects, alleviating bone destruction in osteoarthritis, we investigated whether this drug inhibits the formation and survival of osteoclast in the periodontitis. Rats were distributed into 3 groups: 1) group with periodontitis treated with 100 mg/kg diacerein (PDG), 2) group with periodontitis treated with saline (PSG) and group control (CG) without any treatment. After 7, 15 and 30 days, the maxillae were collected for light and transmission electron microscopy analyses. Gingiva samples were collected to evaluate the mRNA levels for Tnf, Il1b, Tnfsf11 and Tnfrsf11b by RT-qPCR. In PDG, the expression of Tnf and Il1b genes reduced significantly compared to PSG, except for Tnf expression at 7 days. The number of osteoclasts reduced significantly in the PDG in comparison with PSG at 7 and 15 days. In all periods, the IL-6 immunoexpression, RANKL/OPG immunoexpression and mRNA levels of Tnfsf11/Tnfrsf11b ratio were significantly lower in PDG than in PSG. PDG exhibited significantly higher frequency of TUNEL-positive osteoclasts than in PSG and CG at all time points. Osteoclasts with caspase-3-immunolabelled cytoplasm and nuclei with masses of condensed chromatin were observed in PDG, confirming osteoclast apoptosis. Diacerein inhibits osteoclastogenesis by decreasing Tnf and Il1b mRNA levels, resulting in decreased RANKL/OPG ratio, and induces apoptosis in osteoclasts of alveolar process of rat molars with periodontitis.

Molecular Signatures of Senescence in Periodontitis: Clinical Insights.

Most of the elderly population is afflicted by periodontal diseases, creating a health burden worldwide. Cellular senescence is one of the hallmarks of aging and associated with several chronic comorbidities. Senescent cells produce a variety of deleterious secretions, collectively termed the senescence-associated secretory phenotype (SASP). This disrupts neighboring cells, leading to further senescence propagation and inciting chronic inflammation, known as "inflammaging." Detrimental repercussions within the tissue microenvironment can trigger senescence at a younger age, accelerate biological aging, and drive the initiation or progression of diseases. Here, we investigated the biological signatures of senescence in healthy and diseased gingival tissues by assessing the levels of key senescence markers (p16, lipofuscin, and ß-galactosidase) and inflammatory mediators (interleukin [IL]-1ß, IL-6, IL-8, matrix metalloproteinase [MMP]-1, MMP-3, and tumor necrosis factor-α). Our results showed significantly increased senescence features including p16, lipofuscin, and ß-galactosidase in both epithelial and connective tissues of periodontitis patients compared with healthy sites in all age groups, indicating that an inflammatory microenvironment can trigger senescence-like alterations in younger diseased gingival tissues as well. Subsequent analyses using double staining with specific cell markers noted the enrichment of ß-galactosidase in fibroblasts and macrophages. Concurrently, inflammatory mediators consistent with SASP were increased in the gingival biopsies obtained from periodontitis lesions. Together, our findings provide the first clinical report revealing susceptibility to elevated senescence and inflammatory milieu consistent with senescence secretome in gingival tissues, thus introducing senescence as one of the drivers of pathological events in the oral mucosa and a novel strategy for targeted interventions.

Galectin-3 inhibition alleviated LPS-induced periodontal inflammation in gingival fibroblasts and experimental periodontitis mice.

OBJECTIVES: Clinical studies have confirmed that galectin-3 (Gal-3) levels are significantly elevated in periodontitis patients. The present study aimed to explore the effects of Gal-3 inhibition on periodontal inflammation in vitro and in vivo. METHODS: Human gingival fibroblasts (HGFs) with or without Gal-3 knockdown were stimulated by lipopolysaccharide (LPS), and a ligation-induced mouse periodontitis model treated with a Gal-3 inhibitor was established. Hematoxylin-eosin (H&E) and immunohistochemistry (IHC) staining were used to evaluate Gal-3 levels in gingival tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect Gal-3, interleukin (IL)-6, IL-8, and C-C motif ligand 2 (CCL2) expression. Immunofluorescence and western blotting were used to detect NF-κB and ERK signaling pathway activation. Micro-computed tomography was used to analyse the degree of bone loss. RESULTS: Gal-3 was significantly up-regulated in inflamed gingival tissues and LPS-induced HGFs. Gal-3 knockdown markedly decreased LPS-induced IL-6, IL-8, and CCL2 expression and blocked NF-κB and ERK signaling pathway activation in HGFs. In the mouse periodontitis model, Gal-3 inhibition significantly alleviated IL-1ß and IL-6 infiltration in gingival tissue and mitigated periodontal bone loss. CONCLUSIONS: Gal-3 inhibition notably alleviated periodontal inflammation partly through blocking NF-κB and ERK signaling pathway activation.

lncRNA CDKN2B-AS1 regulates collagen expression.

The long noncoding RNA CDKN2B-AS1 harbors a major coronary artery disease risk haplotype, which is also associated with progressive forms of the oral inflammatory disease periodontitis as well as myocardial infarction (MI). Despite extensive research, there is currently no broad consensus on the function of CDKN2B-AS1 that would explain a common molecular role of this lncRNA in these diseases. Our aim was to investigate the role of CDKN2B-AS1 in gingival cells to better understand the molecular mechanisms underlying the increased risk of progressive periodontitis. We downregulated CDKN2B-AS1 transcript levels in primary gingival fibroblasts with LNA GapmeRs. Following RNA-sequencing, we performed differential expression, gene set enrichment analyses and Western Blotting. Putative causal alleles were searched by analyzing associated DNA sequence variants for changes of predicted transcription factor binding sites. We functionally characterized putative functional alleles using luciferase-reporter and antibody electrophoretic mobility shift assays in gingival fibroblasts and HeLa cells. Of all gene sets analysed, collagen biosynthesis was most significantly upregulated (Padj=9.7 × 10- 5 (AUC > 0.65) with the CAD and MI risk gene COL4A1 showing strongest upregulation of the enriched gene sets (Fold change = 12.13, Padj = 4.9 × 10- 25). The inflammatory "TNFA signaling via NFKB" gene set was downregulated the most (Padj=1 × 10- 5 (AUC = 0.60). On the single gene level, CAPNS2, involved in extracellular matrix organization, was the top upregulated protein coding gene (Fold change = 48.5, P < 9 × 10- 24). The risk variant rs10757278 altered a binding site of the pathogen responsive transcription factor STAT1 (P = 5.8 × 10- 6). rs10757278-G allele reduced STAT1 binding 14.4% and rs10757278-A decreased luciferase activity in gingival fibroblasts 41.2% (P = 0.0056), corresponding with GTEx data. CDKN2B-AS1 represses collagen gene expression in gingival fibroblasts. Dysregulated collagen biosynthesis through allele-specific CDKN2B-AS1 expression in response to inflammatory factors may affect collagen synthesis, and in consequence tissue barrier and atherosclerotic plaque stability.

Prevalence of Histopathologic Types of Gingival Lesions in the Iranian Population: A 22-Year Retrospective Study.

OBJECTIVES: Gingiva is one of the supporting tissues around the teeth that can be affected by various neoplastic or nonneoplastic lesions. Previous studies have examined several types of gingival lesions, but the lack of a standardized classification system has hindered meaningful comparisons. Additionally, many studies focused primarily on reactive lesions. Our study aims to contribute to the understanding of gingival lesions by investigating their prevalence across age groups, genders, sites, and by their clinical presentation. This research could lead to improved diagnostic accuracy and treatment strategies. MATERIALS AND METHODS: This retrospective study explores the prevalence of gingival lesions based on biopsies during a 22-year span. The patient's demographic details, including age, gender, and lesion's clinical presentation were systematically collected. These lesions were categorized into six groups. Descriptive statistics, χ2 test of independence, and one-way ANOVA were used for data analysis. RESULTS: Among the 7668 biopsied lesions, 684 (8.9%) lesions were located in the gingiva, with a greater occurrence in women (63.5%). Soft tissue tumors represented the most prevalent group in the gingival lesions (72.1%), and peripheral giant cell granuloma (PGCG) was the most frequent lesion (21.2%), followed by, pyogenic granuloma (19.3%), peripheral ossifying fibroma (17.8%) and focal fibrous hyperplasia (7.6%); all of which predominantly affected women, with mean ages falling in the fourth decade of life. Squamous cell carcinoma was recognized as the most common malignancy. CONCLUSION: In this study, PGCG was found to be the most common lesion in the gingiva in Iranian population. Further analysis using a unanimous categorization is required to confirm these results.