Gingival Tissue Research Articles

Neutrophil extracellular traps in the cross-talk between periodontitis and chronic kidney disease

BackgroundThe objective was to evaluate the level of neutrophil extracellular traps (NETs) in patients with chronic kidney disease (CKD) and periodontitis, and to explore the relationship between NETs and both diseases.Methods63 CKD and 40 non-CKD participants were recruited and underwent periodontal examination, among which 35 early CKD patients underwent periodontal therapy. The concentrations of NETs were determined by dsDNA assay in gingival crevicular fluid (GCF) and plasma, and by flow cytometry or immunofluorescence assay in blood and gingival tissues. The correlations between NETs and clinical parameters were analyzed. The influence of periodontal therapy on periodontitis, CKD and NETs concentrations was also evaluated.ResultsCKD patients had higher concentrations of NETs in plasma than non-CKD patients, and NETs concentrations were also increased in both GCF and plasma of patients with periodontitis than that of periodontally healthy patients. NETs concentrations were positively correlated with increased clinical parameters of CKD and periodontitis. The positive correlation between CKD and periodontitis was demonstrated. Moreover, periodontal therapy ameliorated periodontitis and CKD, and reduced NETs concentrations in GCF of patients.ConclusionsThis study revealed that NETs might be a possible bridge between periodontitis and CKD, and suggested the potential target for therapy.

Protective effects of a lactobacilli mixture against Alzheimer’s disease-like pathology triggered by Porphyromonas gingivalis

Porphyromonas gingivalis (P. gingivalis) is one of the pathogens involved in gingival inflammation, which may trigger neuroinflammatory diseases such as Alzheimer’s disease (AD). This study aimed to investigate the protective (preventive and treatment) effects of a lactobacilli mixture combining Lactobacillus reuteri PTCC1655, Lactobacillus brevis CD0817, Lacticaseibacillus rhamnosus PTCC1637, and Lactobacillus plantarum PTCC1058 against P. gingivalis-induced gingival inflammation and AD-like pathology in rats. These probiotic strains exhibited cognitive enhancement effects, but this study proposed to assess their activity in a mixture. To propose a probable mechanism for P. gingivalis cognitive impairments, the TEs balance were analyzed in hippocampus and cortex tissues. Animals were divided into five groups: the control, lactobacilli, P. gingivalis, lactobacilli + P. gingivalis (prevention), and P. gingivalis + lactobacilli group (treatment) groups. The behavioral and histopathological changes were compared among them. Finally, The Trace elements (TEs) levels in the hippocampus and cortex tissues were analyzed. The palatal tissue sections of the P. gingivalis infected rats showed moderate inflammation with dense infiltration of inflammatory cells, a limited area of tissue edema, and vascular congestion. Additionally, passive avoidance learning and spatial memory were impaired. Histopathological tests revealed the presence of Aβ-positive cells in the P. gingivalis group. While the Aβ-positive cells decreased in the treatment group, their formation was inhibited in the preventive group. Administration of a mixture of lactobacilli (orally) effectively mitigated the gingival inflammation, Aβ production, and improved learning and memory functions. Moreover, Zn, Cu, and Mn levels in the hippocampus were dramatically elevated by P. gingivalis infection, whereas lactobacilli mixture mitigated these disruptive effects. The lactobacilli mixture significantly prevented the disruptive effects of P. gingivalis on gingival and brain tissues in rats. Therefore, new formulated combination of lactobacilli may be a good candidate for inhibiting the P. gingivalis infection and its subsequent cognitive effects. The current study aimed to evaluate the effects of a lactobacilli mixture to manage the disruptive effects of P. gingivalis infection on memory.

Diabetes mellitus exacerbates inflammation in a murine model of ligature-induced peri-implantitis: A histological and microtomographic study.

To investigate the influence of diabetes mellitus (DM) in a murine model of peri-implantitis (PI). Twenty-seven 4-week-old C57BL/6J male mice had their first and second maxillary left molars extracted. Eight weeks later, one machined implant was placed in each mouse. Four weeks after osseointegration, the mice were divided into three groups: (a) control (C), (b) PI and (c) DM + PI. DM was induced by streptozotocin (STZ) administration. After DM induction, PI was induced using ligatures for 2 weeks. The hemimaxillae were collected for micro-CT and histological analyses. The primary outcomes consisted of linear (mm) and volumetric (mm3) bone loss. Secondary outcomes were based on histological analysis and included inflammatory infiltrate, osteoclastic activity, matrix organization, composition and remodelling. Data are presented as means ± SEM. Statistical analyses were performed using one-way ANOVA, followed by Tukey's test. Gingival tissue oedema was detected in the PI and DM + PI groups. Micro-CT showed significantly increased linear and volumetric bone loss in the DM + PI group compared to the C and PI groups. H&E staining showed greater inflammatory response and bone resorption in the PI and DM + PI groups than in the C group. The DM + PI group had significantly higher osteoclast numbers than the C and PI groups. Picrosirius red stained less for types I and III collagen in the PI and DM + PI groups than in the C group. There was a significant increase in monocyte/macrophage (CD-11b) counts and matrix metalloproteinases (MMP-2 and MMP-8) marker levels and a significant decrease in the matrix metalloproteinases inhibition marker (TIMP-2) levels in the DM + PI group compared to the C and PI groups. DM exacerbates PI-induced soft-tissue inflammation, matrix degradation and bone loss.

D-mannose alleviates chronic periodontitis in rats by regulating the functions of neutrophils

BackgroundPeriodontitis is a chronic inflammatory disease characterized by the destruction of the components of the periodontium. It significantly impacts oral health and has been linked to systemic conditions like cardiovascular disease and diabetes. The critical role of neutrophils in the occurrence and development of chronic periodontitis has been paid increasing attention. The study aimed to explore the protective effects of D-mannose on chronic periodontitis and determine whether its underlying mechanisms is related to neutrophils.MethodsTo explore the protective effects of D-mannose on chronic periodontitis, the eight-week-old Sprague Dawley rat model of lipopolysaccharide (LPS)-induced periodontitis was established, followed by D-mannose treatment by oral gavage. To evaluate the protective effects of D-mannose against periodontal bone loss, methylene blue staining, hematoxylin and eosin (H&E) staining, and micro-CT scanning were utilized. Then, immunofluorescence (IF), Western Blot, and RT-PCR were applied to assess the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, and IL-17), anti-inflammatory cytokine (IL-10), tumor necrosis factor-alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), ten-eleven translocation 2 (TET2), and key glycolytic enzymes (HK1, HK2, PFKFB3), and to examine D-mannose’s impact on the recruitment and activation of neutrophils in the gingiva. Additionally, neutrophils isolated from the peripheral blood of healthy rats were treated with LPS and D-mannose, and changes in the expression levels of myeloperoxidase (MPO), IL-1β, IL-6, IL-17, IL-10, and TET2 were observed via IF.ResultsIn vivo, D-mannose inhibited LPS-induced alveolar bone resorption in rats. After D-mannose treatment, the expression levels of IL-17 (p<0.01) and TET2 (p<0.01) were suppressed by IF, and the expression levels of IL-1β (p<0.05), IL-17 (p<0.05) and TET2 (p<0.01) were downregulated by WB. The results of qPCR showed that D-mannose reduced the expression levels of IL-1β (p<0.05), IL-6 (p<0.01), IL-17 (p<0.01), TNF-α (p<0.01), G-CSF (p<0.01), GM-CSF (p<0.01), TET2 (p<0.01), HK1 (p<0.01), HK2 (p<0.01), and PFKFB3 (p<0.01). D-mannose also inhibited the recruitment and activation of neutrophils in LPS-treated rat gingival tissues. In vitro, the results of IF showed that D-mannose inhibited the activation of neutrophils stimulated by LPS, downregulated the expression of IL-1β (p < 0.05), IL-6, IL-17 (p < 0.01), and TET2 (p < 0.01), and upregulated the expression of IL-10 (p < 0.01).ConclusionsD-mannose can alleviate chronic periodontitis in rats by regulating the functions of neutrophils, potentially associated with the expression of TET2 and glycolysis, providing new insights into the potential application of D-mannose to chronic periodontitis.

The Effect of the Root Bark of Lycium chinense (Lycii Radicis Cortex) on Experimental Periodontitis and Alveolar Bone Loss in Sprague-Dawley Rats

Lycii Radicis Cortex (LRC), the dried root bark of Lycium chinese Mill., has traditionally been used as a medicinal herb in East Asia to treat fever and hyperhidrosis. In the present study, we investigated the effects of LRC extract on ligation-induced experimental periodontitis and associated alveolar bone loss in rats. Twenty-four hours after ligation placement, LRC was orally administered once daily for 10 days. Firstly, LRC administration inhibited anaerobic bacterial proliferation and inflammatory cell infiltration in gingival tissues. Additionally, LRC exhibited anti-inflammatory effects by reducing the expression of inflammatory mediators, including prostaglandin E2, interleukin-1β, and tumor necrosis factor-α. LRC treatment also downregulated mRNA expression of these inflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 cells by inhibiting the mitogen-activated protein kinases and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, LRC showed an antioxidant effect by decreasing the malondialdehyde level and inducible nitric oxide synthase activity in gingival tissues. Moreover, LRC effectively prevented the connective tissue degradation by inhibiting matrix metalloproteinase-8 expression and the loss of collagen-occupied areas in gingival tissues. LRC also decreased the receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) ratio, as well as the number and occupied areas of osteoclasts on the alveolar bone surface, thereby inhibiting alveolar bone loss. In summary, these findings suggest that LRC is a promising medicinal herb for alleviating periodontitis and related alveolar bone loss through its antimicrobial, anti-inflammatory, and antioxidant properties.

MANEJO DO SORRISO GENGIVAL ATRAVÉS DO USO DA TOXINA BOTULÍNICA TIPO A

An aesthetically pleasing smile results from the combination of several factors, such as the position, size, shape, and color of the teeth, as well as the exposure and characteristics of the gingival tissue. When evaluating the gingival tissue in a smile, several important factors must be considered: excessive vertical growth of the maxilla, reduced length of the upper lip, excessive contraction of the upper lip, and disproportion between the length and width of the clinical crown of the anterior teeth. A minimally invasive approach that can be used as a complement to dental treatment is the application of botulinum toxin, a neurotoxin produced by the anaerobic bacterium Clostridium botulinum. This toxin blocks the release of acetylcholine in the presynaptic vesicles of neuromuscular junctions, inhibiting muscle contraction. The aim of this literature review was to analyze the use of botulinum toxin type A (BTX-A) in the management of gummy smile. The search was conducted in the databases Google Scholar, PubMed, Latin American and Caribbean Health Sciences Literature (LILACS), and Scientific Electronic Library Online (SciELO). The descriptors used for the search were "botulinum toxin," "gingiva," "periodontology," and "dental aesthetics," combined using the boolean operators AND and OR. Although the evidence demonstrates favorable results, the use of botulinum toxin to correct gummy smile has limitations. It is a temporary solution, and patients should be informed about the need for periodic reapplications and the potential side effects, such as facial asymmetries. The reviewed studies indicate that this technique is particularly effective in cases of gummy smile resulting from hyperactivity of the upper lip elevator muscle, providing a significant reduction in gingival exposure, with results lasting up to 12 weeks. The combination of different therapeutic approaches, along with a careful evaluation of the causes of gummy smile, allows dental professionals to offer more integrated and personalized solutions for each patient.

Soft Tissue Changes at the Pontic Sites of Cantilever Zirconia Ceramic Resin-Bonded Fixed Dental Protheses inthe Esthetic Zone: A Clinical Observational Study.

Data on the stability of soft tissues at pontic sites of resin-bonded fixed dental protheses (RBFDP) are lacking. The purpose of this study was to evaluate soft tissue changes at pontic sites of cantilever zirconia ceramic RBFDPs with and without surgical pretreatment after different follow-up periods in the esthetic zone. Impressions were taken after the insertion of the restorations and an intraoral scan was performed at follow-up examinations. Dental casts were digitalized and superimposed with the follow-up scan. Vertical and horizontal soft tissue changes were measured buccally and lingually at mucosal margin at the central cross-section of each pontic, and for horizontal change at 1 and 2 mm below. One-way ANOVA and Kruskal-Wallis test were performed to analyze the collected data. A total of 36 pontic sites with (n = 7) and without surgical pretreatment (n = 29) were evaluated at a follow-up period of either > 4, > 6, or > 10 years (n = 12). The follow-up period had no significant effect on the tissue change. Surgical pretreatment showed significantly higher tissue loss at 2 mm below the lingual mucosal margin than for sites without surgical pretreatment. Soft tissues at pontic sites remained stable with a tissue gain at the mucosal margin up to 10 years. Based on the findings of this study, cantilever resin-bonded fixed dental protheses provide excellent functional and esthetic outcomes with preservation of soft tissues in the edentulous area of single missing incisors and a gingival sulcus-like tissue growth at the mucosal margin forming an emergence profile at pontic sites similar to that of a natural tooth.

Heterotopically differentiated PDLSCs-laden 3D bioprinting scaffolds for concurrent oral hard and soft tissue regeneration

Following dental extraction, the alveolar bone and gingival tissues could undergo varying degrees of resorption, affecting subsequent implant integration and aesthetic outcomes. Adequate volume of both hard and soft tissues is essential for optimal results. Three-dimensional (3D) bioprinting technology offers the advantages of biomimicry, personalization, and precise spatial distribution, which are pivotal for enhancing the success and esthetics of dental restorations. In this study, we fabricated a construct with a natural transition and varying material concentrations by 3D bioprinting, comprising an upper layer of Collagen/Alginate/periodontal ligament stem cells (PDLSCs) and a lower layer of Collagen/nano-hydroxyapatite (nHA)/Alginate/PDLSCs. Characterization of the physicochemical properties revealed that the incorporation of nHA significantly enhanced the mechanical properties of both the bioink and the construct. Flow cytometry analysis confirmed the stemness of PDLSCs. Scanning electron microscopy (SEM) revealed that the construct possesses satisfactory pore density and a natural transition at the stratification point. The construct displayed good cell viability and proliferation, with the cellular movement observed at the stratification interface after bioprinting. Differentiation staining and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) results demonstrated that PDLSCs within the 3D construct are capable of both osteogenic and fibroblastic differentiations. Ectopic transplantation in mice confirmed the biocompatibility of the construct. A rat tooth extraction model validated the construct's effectiveness in the integrated regeneration of both hard and soft tissues in alveolar ridge preservation (ARP). In conclusion, this personalized, concentration-varied 3D construct exhibits excellent biocompatibility and tissue preservation effects, holding significant potential for clinical application. &amp;nbsp;

Survey on Patient Perception of At-Home Bacterial Biofilm Control in Relation to Peri-Implant Soft Tissue Health.

Bacterial biofilm control around dental implants is critical for the health of the peri-implant soft tissue and longevity of dental implants. The patient's role in regular biofilm removal around dental implants is just as important as that of the dental hygienist. The purpose of this study is to identify the relationship between at-home dental implant care and patients' perceptions of peri-implant soft tissue health. A 15-item paper survey was distributed to adult patients undergoing professional dental hygiene maintenance at a specialty dental practice within a 3-month period and had at least one dental implant. Survey items included participant demographics, patient-reported adjunctive aids for dental implants and patient perceptions of dental implant oral hygiene practices and peri-implant soft tissue health. There was a statistical difference between time spent cleaning dental implants and peri-implant soft tissue health. An association was found between patients who reported spending more time cleaning their dental implants and less bleeding (p = 0.046/54%), gingival inflammation (p = 0.026/58%) and gingival tissue redness (p = 0.036/53%). Additionally, patients who more frequently underwent professional dental hygiene maintenance perceived less gingival inflammation (p = 0.001/66%). To promote peri-implant soft tissue health and reduce oral biological complications, best practice guidelines should be implemented, including optimal at-home dental implant care and regular professional dental hygiene maintenance.

SLC37A4, gene responsible for glycogen storage disease type 1b, regulates gingival epithelial barrier function via JAM1 expression

Solute carrier family 37 member 4 (SLC37A4) is known to regulate glucose-6-phosphate transport from cytoplasm to the lumen of the endoplasmic reticulum, which serves to maintain glucose homeostasis. Glycogen storage disease type 1b (GSD1b) is caused by a mutation of SLC37A4, leading to a glycogenolysis defect. Although GSD1b cases are known to be complicated by periodontitis, the etiological molecular basis remains unclear. The present study investigated the effects of SLC37A4 on gingival barrier function. Examinations of immortalized human gingival epithelial (IHGE) cells showed SLC37A4 localized in the endoplasmic reticulum. SLC37A4 knockout decreased expression of JAM1, a tight junction-related protein, in IHGE cells. Using in silico analysis to investigate potential transcription factor binding sites, H6 family homeobox 3 (HMX3) was shown to be related to JAM1 expression. In HMX3-knockdown IHGE cells, JAM1 expression was markedly suppressed. Furthermore, HMX3 was scarcely detected in SLC37A4-knockout cells, while HMX3 overexpression restored JAM1 expression in those cells. Finally, using a three-dimensional multilayered gingival epithelial tissue model, knockout of SLC37A4 was also found to increase permeability to lipopolysaccharide and peptidoglycan, which was dependent on JAM1 expression. Specific downregulation of HMX3 by SLC37A4 and the consequent decrease in JAM1 expression provides findings indicating a molecular basis for the reduction in barrier function of gingival epithelial tissues in GSD1b cases.

The Effect of Carbodiimide Crosslinkers on Gelatin Hydrogel as a Potential Biomaterial for Gingival Tissue Regeneration

Connective tissue grafts for gingival recession treatment present significant challenges as they require an additional surgical site, leading to increased morbidity, extended operative times, and a more painful postoperative recovery for patients. Gelatin contains the arginine–glycine–aspartic acid (RGD) sequence, which supports cell adhesion and interactions. The development of gelatin hydrogels holds significant promise due to their biocompatibility, ease of customization, and structural resemblance to the extracellular matrix, making them a potential candidate for gingival regeneration. This study aimed to assess the physical and biological properties of crosslinked gelatin hydrogels using EDC/NHS with two crosslinker concentrations (GelCL12 and GelCL24) and compare these to non-crosslinked gelatin. Both groups underwent morphological, rheological, and chemical analysis. Biological assessments were conducted to evaluate human gingival fibroblast (HGF) proliferation, migration, and COL1 expression in response to the scaffolds. The crosslinked gelatin group exhibited greater interconnectivity and better physical characteristics without displaying cytotoxic effects on the cells. FTIR analysis revealed no significant chemical differences between the groups. Notably, the GelCL12 group significantly enhanced HGF migration and upregulated COL1 expression. Overall, GelCL12 met the required physical characteristics and biocompatibility, making it a promising scaffold for future gingival tissue regeneration applications.

Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease

AbstractMinocycline is a commonly used drug for adjunctive therapy in periodontal disease. However, the current mainstream local medications primarily rely on intra‐pocket administration, which, while avoiding the side effects of traditional systemic drugs, presents challenges such as inconvenience, discomfort, and the need for professional assistance, thus affecting patient compliance. Herein, we introduce a minocycline‐loaded dissolvable microneedle (Mino‐DMN) patch that allows for local and efficient delivery of minocycline to gingiva for the treatment of periodontitis. A two‐step casting micro‐molding process involving vacuum drying and freeze drying is employed to concentrate minocycline in the microneedle part and limit its diffusion into the patch backing. The resulting Mino‐DMN patch features an array of minocycline‐enriched gelatin MNs with a porous HA patch backing. The microneedles can penetrate into gingiva with enough mechanical strength and quickly release minocycline into the gingival tissue, ensuring prolonged local residence of the drug and minimizing its loss to saliva. In vivo experiments show Mino‐DMN inhibits pro‐inflammatory factors, promotes anti‐inflammatory factors, and stimulates bone formation, surpassing topical application and comparable to the inconvenient and discomfort administration of Periocline®. This proposed Mino‐DMN offers a simple, efficient, user‐friendly strategy for the adjunctive treatment of periodontal disease.

Modulation of NRF2/KEAP1 Signaling by Phytotherapeutics in Periodontitis.

Periodontitis affects up to 40% of adults over 60 years old and is a consequence of gingivitis. Periodontitis is characterized by a chronic inflammation, periodontal damage, and alveolar bone resorption. The nuclear factor erythroid 2-related factor 2 (NFE2L2 or NRF2)/Kelch-like ECH-Associated Protein 1 (KEAP1) (NRF2/KEAP1) signaling pathway plays a key role in periodontitis by modulating redox balance and inflammation of the periodontium. However, NRF2 expression is decreased in gingival tissues of patients with periodontitis while oxidative stress is significantly increased in this pathology. Oxidative stress and lipopolysaccharide (LPS) produced by gram-negative bacteria favor the production of inflammatory causing periodontal inflammation and favoring alveolar bone. In this review, we analyzed the current literature regarding the role of natural and synthetic compounds in modulating the NRF2/KEAP1 pathway in in vitro and in vivo models of periodontitis in order to evaluate new potential treatments of periodontitis that can improve the outcome of this disease.

GINGIVAL MARGIN, CORRECTION IN ORTHOPEDIC DENTISTRY

A big problem for obtaining aesthetic and functional results of dental treatment is the condition of the gingival papillae. The effectiveness of orthopedic interventions without high-quality correction of the marginal edge of the gums can lead to an unsatisfactory result and the occurrence of numerous complications Materials and methods. A literature search was conducted in the PubMed and Medline databases for the period 2000-2024, for which the following keywords were used: correction of soft gingival tissues, fixed dentures, effectiveness, front group of teeth. A general search revealed 112 sources regarding gingival margin correction in fixed dentures. The primary exclusion referred to literary sources in which the correction of the gingival margin applied to all types of prosthetics. Literary sources that contained only reference information were included in the secondary exclusion. As a result, only relevant full-text articles in professional journals remained (n=25). The purpose of the research is to analyze the methods of gingival margin correction in orthopedic dentistry at the current stage, to formulate relevant tasks for further research. Research results. Methods of restoration of the aesthetics of the marginal part of the gums during orthopedic treatment are divided into the following groups: plastic of soft and bone tissues; laboratory and technical procedures; use of materials for artificial gums. It has been established that the plastic-surgical method is used for the loss of the gingival papilla, defects of the ridge of the alveolar process, asymmetric contour of the gums, and their unaesthetic shape. Correction of the gums allows to achieve satisfactory aesthetic results both at the final stage of orthopedic treatment (prosthetics with fixed orthopedic prostheses) and at the intermediate stage of temporary prosthetics with plastic fixed prostheses. It was found that the most common methods of gingival margin correction are flap operations on the gums using the technique of lateral movement of the muco-osseous flap. These include the following types of interventions: endothelial modification from the tooth-alveolar ridge; oblique displaced flap; periosteally stimulated flap; partial or complete split flap. The positive effect of hyaluronic acid on the healing of the gingival margin and tissue regeneration has been proven. Several researches have shown the positive effects of hyaluronic acid on gingival margin healing and tissue regeneration due to its properties to stimulate cell adhesion, migration and proliferation, mediate cell signaling. The authors indicate a better effectiveness of hyaluronic acid in relation to periodontal parameters during the correction of the marginal gingival margin. The use of a laser scalpel is characterized by less pronounced traumatization of tissues, lower temporary costs for intervention, reduced blood loss, less pronounced signs of inflammation in the postoperative period, relative simplicity and cost-effectiveness of use. Conclusions. To date, only a combination of various orthopedic and surgical manipulations allows to achieve an optimal aesthetic result during prosthetics with fixed dentures of the front group of teeth.

Mulberry lesion: Fibro-epithelial hyperplasia with an unusual clinical presentation

Fibro-epithelial hyperplasia comes under the category of reactive lesions which are basically progressive fibrous overgrowths which arise from the gingival connective tissue and periodontal ligament fibres and are presented in the oral cavity due to long standing local irritation which are not neoplastic and/or may cause esthetic and functional problems. Following case is presented describing an unusual type of clinical presentation of a long standing fibro-epithelial hyperplasia in a 55 year old female with a history of 3 years which was excised using a scalpel and was sent for a histopathogical analysis.

Periodontal Evaluation for a New Alkasite Restorative Material in Noncarious Cervical Lesions: A Randomized-Controlled Clinical Trial.

This study aims to evaluate the periodontal condition adjacent to Cention N (CN) restorations applied for noncarious cervical lesions (NCCL) compared with resin-modified glass ionomer cement (RM-GIC) restorations in terms of plaque accumulation, attachment loss, and gingival inflammation. This is a double-blind split-mouth three-armed randomized-controlled clinical trial. The study arms are RM-GIC (FUJI II LC), CN + adhesive system, and CN + retentive groove. The study included 25 restorations per arm. Follow-ups were performed at 1 week, 3, 6, and 9 months after the application of the restorations. The periodontal condition was evaluated using the plaque index (PI), the bleeding on probing index (BOP), and the probing depth (PD). Appropriate tests were used to perform statistical analyses (α = 0.05). There was no significant difference between Cention N and RM-GIC regarding the studied variables. However, after the application of the restorations, it was noted that the PI and the PD mean values increased. The average increase after 9 months was 0.06 and 0.34 for PI and PD, respectively, with that of PD being significant. It was also noted that the percentage of positive BOP sites increased at the 1-week follow-up for all study groups and afterward dropped to near preintervention values at the 3-month and later follow-ups. The two ion-releasing materials Cention N and RM-GIC have a comparable and clinically acceptable effect on the gingival tissue when restoring NCCLs. The combined effect of the gingival retraction cord and the rubber dam clamp on the periodontal tissues might be more important to consider, especially in relation to the probing depth. Future long-term studies are needed to evaluate the effect of Cention N on the subgingival biofilm in comparison with nonion-releasing restorative materials, and subsequently, its effect on gingival inflammation. This clinical trial was registered in clinicaltrial.gov clinical registry under protocol #NCT05593159.

Impacts of Hyperglycemia on Epigenetic Modifications in Human Gingival Fibroblasts and Gingiva in Diabetic Rats

Periodontal disease is considered one of the diabetic complications with high morbidity and severity. Recent studies demonstrated the involvement of the epigenome on diabetic complications. Histone modifications change chromatin architecture and gene activation. Histone modifications have been reported to alter chromatin structure and regulate gene transcription. In this study, we investigated the impacts of H3 lysine 4 trimethylation (H3K4me3) and specific histone methyltransferases of H3K4 methylation, su(var)3-9, enhancer-of-zeste, and trithorax domain 1A (SETD1A) on periodontal tissue affected by the diabetic condition. We observed the increase in H3K4me3 and SETD1A in gingival tissue of diabetic rats compared with the normal rats. Cultured human fibroblasts (hGFs) confirmed a high glucose-induced increase in H3K4me3 and SETD1A. We further demonstrated that high glucose increased the gene expression of matrix metalloproteinase (MMP) 1 and MMP13, which were canceled by sinefungin, an SETD1A inhibitor. Our investigation suggests that diabetes triggers histone modifications in the gingival tissue, resulting in gingival inflammation. Histone modifications may play crucial roles in the development of periodontal disease in diabetes.

Response of a Blood Clot Adherent to Bone, Oral Mucosa and Hard Dental Tissues to a Uniaxial Tensile Test: An In Vitro Study.

Background and Objectives: Periodontal therapy aims to arrest the progression of periodontal diseases and possibly to regenerate the periodontal apparatus. To shift healing from repair to regeneration, the blood clot that fills the periodontal defect and remains in contact with structures such as tooth root, mucosa and bone needs to be stable, which is a reason why the treatment of non-containing periodontal bone defects, in which the clot may undergo displacement, is challenging. The gingival soft tissue, properly sutured, may act as a wall for blood clot stabilization. Knowledge on the response of the blood clot to stress and how it might vary according to the characteristics of the tissues it gets in contact with might be deepened. The aim of this study was to investigate in vitro, by means of a micro-loading device, the response of the complex formed by a blood clot and diverse tissues, simulating those involved in periodontal regeneration, to a displacing tensile test. Materials and Methods: Experimental samples made of two layers of either hard dental tissues, cancellous bone or oral mucosa, between which fresh blood was interposed, underwent a debonding experiment by means of a micro-loading device that measured their response to uniaxial tensile stress. Results: The peak of tensile stress and the overall work needed for the complete rupture of the clot's fibrin filaments were significantly higher for hard dental tissues than for other tissues. However, mucosa sustained the highest maximal strain in terms of relative displacement between the plates of the micro-loading device to accomplish the complete rupture of the fibrin filaments compared to the other tissues, suggesting that the mucosa might act as a stable interface with the clot and be able to sustain tensile stresses. Conclusions: This in vitro study seems to support the use of mucosa to act as a wall for regenerative procedures of suprabony periodontal defects given its capability to form a stable interface with the clot.

Nootkatone mitigates periodontal inflammation and reduces alveolar bone loss via Nrf2/HO-1 and NF-κB pathways in rat model of periodontitis.

Periodontitis (PD) is a chronic inflammatory disease leading to alveolar bone loss. This study investigated the effect of nootkatone and regulatory mechanism in reducing periodontal inflammation and alveolar bone loss in a rat model. Twenty male Sprague-Dawley rats were divided into control, periodontitis, and nootkatone-treated groups (45 or 90 mg/kg). Ligature induction method was adopted to establish the PD model. After 21 days, rats received daily gavage of either saline or nootkatone for 10 days. Alveolar bone loss was assessed using micro-CT. Histological analyses included hematoxylin and eosin (H&E), tartrate-resistant acid phosphatase (TRAP), and Masson's trichrome stainings. Immunohistochemistry for heme oxygenase 1 (HO-1) and nuclear factor erythroid-2 related factor 2 (Nrf2) were performed in periodontal tissues. Content of inflammatory cytokines IL-1β, IL-6, and TNF-α in gingival tissues around ligature were assessed using ELISA kits. Malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were analyzed and Western blot for NF-κB expression in gingival tissues were performed. Nootkatone significantly reduced the distance from cementoenamel junction to alveolar bone crest (CEJ-ABC), enhanced bone mineral density (BMD), bone volume (BV), and BV/total volume (TV) ratio in ligature-induced rats. Higher dose of nootkatone (90 mg/kg) did not show more significant therapeutic effect than lower dose (45 mg/kg). Histological staining showed decreased osteoclasts' number and improved bone architecture in the nootkatone group. Content of IL-1β, IL-6, and TNF-α and inflammatory cell infiltration level in gingival tissues around the ligature were decreased in the nootkatone-treatment rats. Nootkatone increased Nrf2 and HO-1 protein expression and decreased NF-κB protein level, suppressing MDA levels and enhancing SOD activity. In a rat model, nootkatone effectively mitigates periodontal inflammation and alveolar bone loss through the Nrf2/HO-1 and NF-κB pathways. These findings suggest nootkatone as a promising therapeutic agent for the treatment of periodontitis.

Spatial Transcriptomics Unravel the Tissue Complexity of Oral Pathogenesis.

Spatial transcriptomics (ST) is a cutting-edge methodology that enables the simultaneous profiling of global gene expression and spatial information within histological tissue sections. Traditional transcriptomic methods lack the spatial resolution required to sufficiently examine the complex interrelationships between cellular regions in diseased and healthy tissue states. We review the general workflows for ST, from specimen processing to ST data analysis and interpretations of the ST dataset using visualizations and cell deconvolution approaches. We show how recent studies used ST to explore the development or pathogenesis of specific craniofacial regions, including the cranium, palate, salivary glands, tongue, floor of mouth, oropharynx, and periodontium. Analyses of cranial suture patency and palatal fusion during development using ST identified spatial patterns of bone morphogenetic protein in sutures and osteogenic differentiation pathways in the palate, in addition to the discovery of several genes expressed at critical locations during craniofacial development. ST of salivary glands from patients with Sjögren's disease revealed co-localization of autoimmune antigens with ductal cells and a subpopulation of acinar cells that was specifically depleted by the dysregulated autoimmune response. ST of head and neck lesions, such as premalignant leukoplakia progressing to established oral squamous cell carcinomas, oral cancers with perineural invasions, and oropharyngeal lesions associated with HPV infection spatially profiled the complex tumor microenvironment, showing functionally important gene signatures of tumor cell differentiation, invasion, and nontumor cell dysregulation within patient biopsies. ST also enabled the localization of periodontal disease-associated gene expression signatures within gingival tissues, including genes involved in inflammation, and the discovery of a fibroblast subtype mediating the transition between innate and adaptive immune responses in periodontitis. The increased use of ST, especially in conjunction with single-cell analyses, promises to improve our understandings of craniofacial development and pathogenesis at unprecedented tissue-level resolution in both space and time.