Umbelliferone reduces inflammation and ligature-induced osteoclastic alveolar bone resorption in mice.

AIMS: This study aimed to investigate the effects of Umbelliferone (UMB) on the inflammation underlying alveolar bone resorption in mouse periodontitis. METHODS: Male Swiss mice subjected to a ligature of molars were grouped as non-treated (NT), received UMB (15, 45, or 135 mg/kg) or saline daily for 7 days, respectively, and were compared with naïve mice as control. Gingival tissues were evaluated by myeloperoxidase (MPO) activity and interleukin-1ß level by ELISA. The bone resorption was directly assessed on the region between the cement-enamel junction and the alveolar bone crest. Microscopically, histomorphometry of the furcation region, immunofluorescence for nuclear factor-kappa B (NF-ĸB), and immunohistochemistry for tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CTSK) were performed. Systemically, body mass variation and leukogram were analyzed. RESULTS: Periodontitis significantly increased MPO activity, interleukin-1ß level, and NF-ĸB+ immunofluorescence, and induced severe alveolar bone and furcation resorptions, besides increased TRAP+ and CTSK+ cells compared with naïve. UMB significantly prevented the inflammation by reducing MPO activity, interleukin-1ß level, and NF-ĸB+ intensity, besides reduction of resorption of alveolar bone and furcation area, and TRAP+ and CTSK+ cells compared with the NT group. Periodontitis or UMB treatment did not affect the animals systemically. CONCLUSION: UMB improved periodontitis by reducing inflammation and bone markers.

Analysis of inflammation and bone remodeling of atmospheric plasma therapy in experimental periodontitis.

BACKGROUND AND OBJECTIVE: The biological effects of atmospheric plasma (cold plasma) show its applicability for controlling the etiological factors that involve tissue repair. Thus, the study evaluated the effect of atmospheric plasma therapy in the control of tissue inflammation and bone remodeling in experimental periodontitis. METHODS: Fifty-six rats were subjected to ligation in the cervical region of the first maxillary molars (8 weeks). The animals were divided into two groups (n = 28): periodontitis without treatment group (P group), and periodontitis with atmospheric plasma treatment group (P + AP group). Tissue samples were collected at 2 and 4 weeks after treatment to analyze the inflammation and bone remodeling by biochemical, histomorphometric, and immunohistochemical analyses. RESULTS: Inflammatory infiltration in the gingival and periodontal ligament was lower in the P + AP group than in the P group (p < .05). The MPO and NAG levels were higher in the P + AP group compared to P group (p < .05). At 4 weeks, the TNF-α level was lower and the IL-10 level was higher in the P + AP group compared to P group (p < .05). In the P + AP group, the IL-1ß level increased in the second week and decreased in the fourth week (p < .05), the number of blood vessels was high in the gingival and periodontal ligament in the second and fourth week (p < .05); and the number of fibroblasts in the gingival tissue was low in the fourth week, and higher in the periodontal tissue in both period (p < .05). Regarding bone remodeling, the RANK and RANKL levels decreased in the P + AP group (p < .05). The OPG level did not differ between the P and P + AP groups (p > .05), but decreased from the second to the fourth experimental week in P + AP group (p < .05). CONCLUSIONS: The treatment of experimental periodontitis with atmospheric plasma for 4 weeks modulated the inflammatory response to favor the repair process and decreased the bone resorption biomarkers, indicating a better control of bone remodeling in periodontal disease.

Injectable platelet rich fibrin effect on laser depigmented gingiva: a clinical randomized controlled split mouth trial with histological assessment.

OBJECTIVE: To determine whether intra-mucosal injection of injectable platelet-rich fibrin (i-PRF) can promote healing after Diode Laser Gingival Depigmentation (DLGD). METHODOLOGY: A total of 20 arch sites of hyperpigmented gingiva of 10 patients underwent DLGD. For each patient, two arch sites were randomly assigned for either intra-mucosal injection of i-PRF (G1-i-PRF) (n=10 sites) or no treatment (G2-Control): (n=10 sites). Wound Healing Score (WHS), patient satisfaction, and Pigmentation Index (DOPI) were measured at 1 week and 1 and 3 months postoperatively. Histological assessment of tissue specimens was performed at baseline and 1 week. RESULTS: The percentage change in WHS at 1 week was significantly higher in G1 (58.34±15.43) compared to G2 (37.50±11.79). At day 1, 50% of patients in G1 were pain free compared with 75% in G2, who had mild pain. Mean DOPI decreased significantly at 3 months in both groups (P-value <0.001), without significant differences between groups. G1 specimens showed significantly higher epithelial thickness (P-value <0.001), as well as a higher number of blood vessels and less percentage of inflammatory cells. CONCLUSIONS: i-PRF demonstrated better clinical and histological healing potential and less patient discomfort compared to sites without treatment after DLGD. Registered at https://clinicaltrials.gov/ as (NCT05283668).

Ulectomy in a patient with nephrotic syndrome under investigation for Galloway-Mowat syndrome: a case report.

The aim of this study is to report a case in which a patient with nephrotic syndrome underwent surgery to remove fibrous gum tissue (ulectomy). An 8-year-old patient, diagnosed with early onset nephrotic syndrome due to a mutation in the NUP107 gene, had received a kidney transplant and was therefore taking various medications, including immunosuppressants. On oral examination, the patient was found to have a fibrous gingiva that was preventing the eruption of the upper permanent central incisors. A ulectomy was performed and the gingival tissue was sent for histopathological analysis, which showed normal aspects. The upper right central incisor was seen in the oral cavity 15 days after surgery. A second procedure was carried out to facilitate the eruption of the upper left incisor, which was visualized in the oral cavity 30 days later. In addition, oral manifestations such as maxillary atresia, ogival palate and mouth breathing were observed. Therefore, the role of the dental surgeon in the lives of transplanted children is considered important, as they often take various medications that can affect their oral health. Thus, early diagnosis and effective treatment will be essential to prevent future malocclusions and thus improve the quality of life of these patients.

Gingival metastasis of angiosarcoma of the breast as a first manifestation of spreading disease: Case report and review of the literature.

BACKGROUND: Angiosarcoma is an aggressive malignant neoplasm of vascular origin. Oral metastases of angiosarcoma are rare and have a non-specific clinical presentation, thus the diagnosis may be challenging. CASE REPORT: Herein we report a case of a 34-year-old female patient after treatment of a high-grade angiosarcoma of the breast, who presented an asymptomatic bleeding purplish nodule in the maxillary interdental papilla between the first and second premolar. A biopsy was performed, and the histological examination revealed infiltration by malignant neoplasm of epithelioid and fusocellular pattern. Immunohistochemical analysis demonstrated that neoplastic cells were positive for ERG and CD31, and negative for cytokeratins AE1/AE3, confirming the diagnosis of metastatic angiosarcoma. After investigation, multiple metastases were discovered. The patient is under management with chemotherapy and palliative radiotherapy for the bone lesions. CONCLUSION: Metastases should be considered in the differential diagnosis of oral lesions in patients with a previous history of cancer. Due to the morphology of angiosarcomas, the metastatic lesions may resemble benign vascular lesions, therefore, biopsy is mandatory to exclude malignancy.

Orofacial Manifestations in a Middle-Aged Woman with Cowden Syndrome: A Case Image.

A 56-year-old Brazilian woman sought dental care, presenting with multiple asymptomatic papillomatous lesions with a coalescent pattern and intermingled cobblestone-like clefts along the alveolar ridge and marginal and attached gingivae. Multiple whitish papules were also observed on the face, neck, and limbs. Incisional biopsies of these lesions were performed. Microscopically, the skin lesion revealed epithelial clear cells and intraepithelial keratinization with areas of orthokeratosis, while the gingival lesions showed a parakeratinized stratified squamous epithelium with collagenous connective tissue. These features were consistent with those of a trichilemmoma and fibroepithelial hyperplasia, respectively. This article illustrates a case of Cowden syndrome (CS), a rare multisystem genetic condition in which both cutaneous and mucosal tissues were affected. Fewer than 40 cases of CS with oral involvement affecting middle-aged adults have been documented hitherto.

Fibroblasts at the curtain call: from ensemble to principal dancers in immunometabolism and inflammaging.

Inflammation is a necessary step in response to injuries, being vital in restoring homeostasis and facilitating tissue healing. Among the cells that play a crucial role in inflammatory responses, stromal cells, including fibroblasts, have an undeniable significance in fine-tuning the magnitude of mediators that directly affect hyper-inflammatory responses and tissue destruction. Fibroblasts, the dominant cells in the gingival connective tissue, are a very heterogeneous population of cells, and more recently they have been receiving well deserved attention as central players and often the 'principal dancers' of many pathological processes ranging from inflammation and fibrosis to altered immunity and cancer. The goal of the current investigation is to dive into the exact role of the stromal fibroblast and the responsible mechanistic factors involved in both regulation and dysregulation of the inflammatory responses. This article reviews the most recent literature on how fibroblasts, in their different activation states or subtypes, play a crucial role in contributing to inflammatory outcomes. We will focus on recent findings on inflammatory diseases. We will also provide connections regarding the stromal-immune relationship, which supports the idea of fibroblast coming out from the 'ensemble' of cell types to the protagonist role in immunometabolism and inflammaging. Additionally, we discuss the current advances in variation of fibroblast nomenclature and division into clusters with their own suggested function and particularities in gene expression. Here, we provide a perspective for the periodontal implications, discussing the fibroblast role in the infection-driven and inflammatory mediated diseases such as periodontitis.

Aging envisage imbalance of the periodontium: A keystone in oral disease and systemic health.

Aging is a gradual and progressive deterioration of integrity across multiple organ systems that negatively affects gingival wound healing. The cellular responses associated with wound healing, such as collagen synthesis, cell migration, proliferation, and collagen contraction, have been shown to be lower in gingival fibroblasts (the most abundant cells from the connective gingival tissue) in aged donors than young donors. Cellular senescence is one of the hallmarks of aging, which is characterized by the acquisition of a senescence-associated secretory phenotype that is characterized by the release of pro-inflammatory cytokines, chemokines, growth factors, and proteases which have been implicated in the recruitment of immune cells such as neutrophils, T cells and monocytes. Moreover, during aging, macrophages show altered acquisition of functional phenotypes in response to the tissue microenvironment. Thus, inflammatory and resolution macrophage-mediated processes are impaired, impacting the progression of periodontal disease. Interestingly, salivary antimicrobial peptides, such as histatins, which are involved in various functions, such as antifungal, bactericidal, enamel-protecting, angiogenesis, and re-epithelization, have been shown to fluctuate with aging. Several studies have associated the presence of Porphyromonas gingivalis, a key pathogen related to periodontitis and apical periodontitis, with the progression of Alzheimer's disease, as well as gut, esophageal, and gastric cancers. Moreover, herpes simplex virus types 1 and 2 have been associated with the severity of periodontal disease, cardiovascular complications, and nervous system-related pathologies. This review encompasses the effects of aging on periodontal tissues, how P. gingivalis and HSV infections could favor periodontitis and their relationship with other pathologies.

In vitro and in vivo study of the pathogenic role of PPARα in experimental periodontitis.

OBJECTIVE: The purpose of this study is to investigate the pathogenic role of PPARα in periodontal antigen treated gingival cells in vitro and in experimental periodontitis in vivo . METHODOLOGY: Gingival fibroblasts, gingival epithelial cells and splenocytes were isolated from C57BL/6J wild type (WT) mice and treated with fixed P. gingivalis at for 48 hours. The mRNA levels of PPARs, TNFα, IL-1ß and IL-10 were detected by Real-time quantitative PCR. Silk ligatures after being soaked in the P.gingivalis suspension were tied around both maxillary second molars of WT mice or PPARα knock-out (KO) mice for two weeks. PPARα agonist fenofibrate and vehicle control were injected into the different side of the palatal gingiva on days 3, 6, and 9. At day 14, bone resorption and gingival mRNA expression levels of PPARs, TNFα, IL-1ß and IL-10 were measured by micro-computed tomography and RT-qPCR respectively. RESULTS: P. gingivalis treatment downregulated the expression of PPARα, but not PPARß or PPARγ, and increased the expression of TNF-α and IL-1ß in Gingival fibroblasts, gingival epithelial cells and splenocytes from WT mice. Gingival mRNA levels of PPARα were significantly decreased in experimental periodontitis in WT mice. The bone loss of PPARα KO mice in experimental periodontitis was significantly higher than WT mice and was not reduced by fenofibrate treatment. Gingival TNFα protein expressions were significantly increased by P. gingivalis associated ligation and decreased by fenofibrate treatment in WT mice but not in PPARα KO mice. CONCLUSION: This study suggests that PPARα plays an essential role in periodontitis.

A rare case of squamous cell carcinoma of the gingiva: A diagnostic challenge.

BACKGROUND: Oral squamous cell carcinoma (OSCC) of the gingiva represents less than 6% of intraoral carcinomas. CASE REPORT: A 51-year-old male patient presented with a history of a symptomatic red spot with periods of remission and recurrence in the mandibular gingiva. On clinical examination red and white areas were observed in the gingiva, particularly around the left lower molars. Diagnosis of gingival lichen planus was suspected and topical corticosteroids was prescribed. A good clinical response was observed with reduction of symptom. The patient remained in regular follow-up and after 9 months, the lesion suddenly changed, became ulcerated and diagnosis of OSCC was established. CONCLUSION: The clinical manifestation of OSCC can eventually mimic other even more common lesions of the oral mucosa, highlighting the importance of considering OSCC as differential diagnosis of any unexplained and persistent lesion in the oral cavity.

Single gingival recession associated with non-carious cervical lesion treated by partial restoration and coronally advanced flap with or without xenogenous collagen matrix: A randomized clinical trial evaluating the coverage procedures and restorative protocol.

BACKGROUND: Evaluate the use of collagen matrix (CM) as adjunctive to coronally advanced flap (CAF versus CAF + CM) to treat gingival recession (GR) associated with non-carious cervical lesion-combined defects (CDs). METHODS: Sixty-two patients presenting 62 CDs (RT1 GR and non-carious cervical lesion (NCCLs) were randomly allocated to either CAF group (n = 31): partial restoration of the NCCL and CAF; or to CAF + CM group (n = 31): partial restoration of the NCCL and CAF associated with CM. Clinical, esthetic, patient-centered outcomes, and restorative parameters were assessed. RESULTS: After 12 months, CD coverage were 55.2% for CAF and 54.4% for CAF + CM (P = 0.8). Recession reduction were 1.9 ± 0.8 mm for CAF and 2.0 ± 0.7 mm for CAF + CM (P = 0.6). CAF+CM resulted in higher increase in keratinized tissue (KT) width (CAF: 0.3 ± 0.7 mm; CAF + CM: 0.9 ± 0.8 mm; P = 0.004) and KT thickness gain (CAF: 0.1 ± 0.3 mm; CAF + CM: 0.7 ± 0.2 mm; P = 0.001). Both treatments presented low postoperative pain and resulted in esthetics improvements. In addition, no restoration was lost, 27.4% showed a reduction of the superficial polishing, and 8% showed marginal staining, but still clinically acceptable. CONCLUSION: Partial resin composite restoration (with the apical limit up to 1 mm of the estimated CEJ) and CAF alone or combined with CM are suitable for treating CDs. The use of CM provided additional benefits in terms of KT width and thickness gain. (NCT03341598).

Hereditary gingival fibromatosis: a case report / Fibromatosis gingival hereditaria: informe de caso

Introduction: Hereditary gingival fibromatosis is a rare disorder with a genetic component that may appear during tooth replacement. This condition can cause functional and aesthetic problems such as malocclusions, diastemas, pain when chewing, dental caries, periodontal disease, delayed eruption, among others. Objective: To report the multidisciplinary treatment provided to a patient with hereditary gingival fibromatosis. Case Report: This report describes the treatment carried out in a thirteen-year-old male patient presenting generalized increase in gingival volume associated with functional and aesthetic compromise and delayed eruption of permanent teeth. After diagnosis, a multidisciplinary intervention was proposed, involving periodontal and pediatric dentistry procedures, which improved the quality of life of the patient both functionally and aesthetically. Conclusion: Hereditary gingival fibromatosis not only affects the dental eruption process, but also causes aesthetic and emotional alterations in the patient. The periodontal procedures significantly improved the appearance, function, and the psychological state of the patient.

Introducción: La fibromatosis gingival hereditaria es una altera-ción poco común, asociada a un componente genético que en ocasiones se hace evidente en el recambio dentario. Este padecimiento puede generar problemas funcionales y estéticos como maloclusiones, diastemas, dolor al masticar, caries, enfermedad periodontal, erupción tardía, entre otros. Objetivo: Reportar el caso clínico con manejo interdisciplinario en un paciente con fibromatosis gingival hereditaria. Reporte de Caso: Se expone el tratamiento realizado en un paciente de trece años, sexo masculino, con aumento de volumen gingival generalizado con compromiso funcional y estético, conjugado con retraso en la erupción de dientes permanentes. Tras diagnóstico se plantea la intervención multidisciplinaria, integrando áreas como periodoncia y odontopediatría; los procedimientos ejecutados permitieron mejorar la calidad de vida desde el punto de vista funcional y estético. Conclusión: La fibromatosis gingival hereditaria no solo desencadena alteración en proceso eruptivo dental, sino también alteraciones estéticas y emocionales en el paciente que la padece. Los procedimientos perio-dontales realizados permitieron de forma categórica la mejora de la estética, función y estado psicológico del paciente.

TMPRSS11a is a novel age-altered, tissue specific regulator of migration and wound healing.

Aging is a gradual biological process characterized by a decrease in cellular and organism functions. Aging-related processes involve changes in the expression and activity of several proteins. Here, we identified the transmembrane protease serine 11a (TMPRSS11a) as a new age-specific protein that plays an important role in skin wound healing. TMPRSS11a levels increased with age in rodent and human skin and gingival samples. Strikingly, overexpression of TMPRSS11a decreased cell migration and spreading, and inducing cellular senescence. Mass spectrometry, bioinformatics, and functional analyses revealed that TMPRSS11a interacts with integrin ß1 through an RGD sequence contained within the C-terminal domain and that this motif was relevant for cell migration. Moreover, TMPRSS11a was associated with cellular senescence, as shown by overexpression and downregulation experiments. In agreement with tissue-specific expression of TMPRSS11a, shRNA-mediated downregulation of this protein improved wound healing in the skin, but not in the skeletal muscle of old mice, where TMPRSS11a is undetectable. Collectively, these findings indicate that TMPRSS11a is a tissue-specific factor relevant for wound healing, which becomes elevated with aging, promoting cellular senescence and inhibiting cell migration and skin repair.

Oral pyogenic granuloma: An 18-year retrospective clinicopathological and immunohistochemical study.

BACKGROUND: Pyogenic granuloma (PG) is a lesion characterized by the proliferation of blood vessels, commonly affecting the skin and the mouth. We aimed to compare clinical, microscopic, and immunohistochemical features of the two types of oral PG: lobular capillary hemangioma (LCH) and non-LCH (NLCH). METHODS: Epidemiological and clinical data from 2000 to 2018 were collected from the archives of our institution, and histopathological sections of PG were reviewed. Immunohistochemical analyses (CD34, D2-40, SMA, mast cell, and Ki-67) were performed in 34 cases. RESULTS: Sixty-two LCH and 107 non-LCH samples were included. The mean (±SD) age of the patients was 38.59 ± 16.96 years; 55.62% were female; 39.64% of cases occurred in the gingiva, 44% of the nodules were pedunculated, and 13.02% of patients reported a history of trauma. NLCH was more prevalent among older patients than LCH. The most prevalent site of LCH was the lips, while NLCH occurred more in the gingiva (P < 0.05). Epithelial atrophy, microvessels, SMA-positive areas, and Ki-67-positive nuclei were more prevalent in LCH (P < 0.05). CONCLUSIONS: PG accounted for 2.25% of lesions archived in the pathology service and most cases were NLCH. LCH and NLCH exhibited clinicopathological differences in terms of age, site, epithelial atrophy, vascularization, and proliferation rate.

Preliminary findings on the possible role of B-lymphocyte stimulator (BLyS) on diabetes-related periodontitis.

The possible role of B-cell growth and differentiation-related cytokines on the pathogenesis of diabetes-related periodontitis has not been addressed so far. The aim of this study was to evaluate the effects of diabetes mellitus (DM) on the gene expression of proliferation-inducing ligand (APRIL) and B-lymphocyte stimulator (BLyS), two major cytokines associated to survival, differentiation and maturation of B cells in biopsies from gingival tissue with periodontitis. Gingival biopsies were obtained from subjects with periodontitis (n = 17), with periodontitis and DM (n = 19) as well as from periodontally and systemically healthy controls (n = 10). Gene expressions for APRIL, BLyS, RANKL, OPG, TRAP and DC-STAMP were evaluated using qPCR. The expressions APRIL, BLyS, RANKL, OPG, TRAP and DC-STAMP were all higher in both periodontitis groups when compared to the control group (p < 0.05). Furthermore, the expressions of BLyS, TRAP and RANKL were significantly higher in the subjects with periodontitis and DM when compared to those with periodontitis alone (p < 0.05). The mRNA levels of BLyS correlated positively with RANKL in the subjects with periodontitis and DM (p < 0.05). BLyS is overexpressed in periodontitis tissues of subjects with type 2 DM, suggesting a possible role of this cytokine on the pathogenesis DM-related periodontitis.

Clinical and radiographic evaluation of the Periodontium with biologic width invasion.

BACKGROUND: The biologic width is defined as the coronal dimension to the alveolar bone that is occupied by healthy gingival tissue. The objective of the present study was to correlate radiographic findings of biologic width invasion with the periodontium status. METHODS: It were included 14 patients with restored teeth with biological width invasion, on the proximal sites, observed clinically and radiographically. 122 proximal sites were evaluated, 61 in the test group (biological width invasion) and 61 in the control group (adequate biological width). Smokers and patients presenting periodontal disease or restorations with contact in eccentric movements, horizontal over-contour or secondary caries were excluded from the sample. The invasion of the biologic width was diagnosed when the distance from the gingival margin of restoration to the bony crest was less than 3 mm. Intrabony defect and bone crest level, as well as, their vertical and horizontal components were radiographically evaluated when present. Plaque index, bleeding on probing, probing depth, gingival recession height, keratinized gingival height and thickness, and clinical attachment level were clinically evaluated. Data were subjected to Spearman's Correlation and Wilcoxon's test. RESULT: The most prevalent tooth with biological width invasion was the first molar. There was a statistically significant correlation between the bone crest (p < 0.001), vertical (p < 0.001) and horizontal (p = 0.001) components. In the test group, there was a statistically significant correlation between bleeding on probing (p < 0.001; r = 0.618) and width of gingival recession (p = 0.030; r = - 0.602) with the intraosseous component; and between keratinized gingival height and bone level (p = 0.037; r = - 0.267). In the control group, there was a correlation between plaque index (p = 0.027; r = - 0.283) with bone level and correlation between keratinized gingival thickness and bone level (p = 0.034; r = - 0.273) and intrabony component (p = 0.042; r = 0.226). CONCLUSION: A statistically significant relationship was found between bleeding on probing and gingival recession in patients who presented intrabony defects due to the invasion of biological width, which may be also related to the thickness of the keratinized gingiva.

Pam2CSK4 (TLR2 agonist) induces periodontal destruction in mice.

Lipoproteins are important bacterial immunostimulating molecules capable of inducing receptor activator of nuclear factor-κB (RANKL) and osteoclast formation in vitro and in vivo . Although these molecules are present in periodontopathogenic bacteria, their role in periodontitis is not known. In this study, we used Pam2CSK4 (PAM2), a synthetic molecule that mimics bacterial lipoprotein, to investigate the effects of lipoproteins on periodontitis in mice. C57BL/6 male mice were randomly divided into three experimental groups: 1) Negative control group: animals received vehicle injection; 2) Positive control group: animals received injection of Escherichia coli lipopolysaccharide (LPS); 3) PAM2 group: animals received PAM2 injection. All the injections were performed bilaterally every other day into the palatal mucosa between first and second molars. After twenty-four days, the animals were euthanized to assess alveolar bone volume (micro-CT), cellular and extracellular composition in the gingiva (stereometric analysis), and osteoclast numbers (TRAP staining). Treatment with either PAM2 or LPS induced gingival inflammation, as demonstrated by increased infiltration of inflammatory cells and enhanced angiogenesis, associated with a smaller number of fibroblasts and decreased extracellular matrix. Importantly, treatment not only with LPS but also with PAM2 resulted in a larger number of TRAP+ multinucleated osteoclasts and significant loss of alveolar bone. Collectively, our data demonstrate that PAM2 can induce gingival inflammation and bone loss in mice, broadening the avenues of investigation into the role of lipoproteins in the pathogenesis of periodontal disease.