RESUMO
Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs) across various organ systems including oral health complications such as dry mouth and stomatitis. In this study, we aimed to determine the risk of periodontitis among patients on immune checkpoint inhibitors (ICIs) and to test the associations between ICI-associated periodontitis and other immune-related adverse events (irAEs). We performed a retrospective cohort study involving adult cancer patients between January 2010 and November 2021. Patients on an ICI were propensity score-matched to patients not on an ICI. The primary outcome was the occurrence of periodontitis. ICIs included programmed cell death 1 (PD-1) inhibitors programmed cell death ligand 1 (PD-L1) inhibitors, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors. The risk of periodontitis following ICI use was derived through a Cox proportional hazard model and Kaplan-Meier survival analysis. Overall, 868 patients on an ICI were matched to patients not on an ICI. Among the ICI cohort, 41 (4.7 %) patients developed periodontitis. The incidence rate of periodontitis was significantly higher in patients on an ICI than in patients not on an ICI (55.3 vs 25.8 per 100 patient-years, incidence rate ratio = 2.14, 95 % CI = 1.38-3.33). Both the use of PD-L1 inhibitors (multivariate HR = 2.5, 95%CI = 1.3-4.7) and PD-1 inhibitors (multivariate HR = 2.0, 95%CI = 1.2-3.2) were associated with the risk of periodontitis. The presence of immune-related periodontitis was associated with better overall survival (not reached vs 17 months, log-rank p-value<0.001), progression-free survival (14.9 vs 5.6 months, log-rank p-value = 0.01), and other concomitant immune-related cutaneous adverse events. In conclusion, ICI was associated with an increased risk of periodontitis. Immune-related periodontitis as an irAE was associated with better cancer survival and concomitant cutaneous irAEs.
Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Periodontite , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Feminino , Periodontite/imunologia , Periodontite/induzido quimicamente , Periodontite/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Incidência , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Adulto , Estimativa de Kaplan-Meier , Fatores de RiscoRESUMO
BACKGROUND: Phthalates are widely used plasticizers, which were identified as risk factors in the development of many human diseases. However, the effects of phthalates in the periodontitis are unknown. We aimed to investigated the relationship of periodontitis and phthalate exposure as well as the underlying mechanisms. MATERIALS AND METHODS: Univariate and multivariate logistic regressions were employed to evaluate the association between phthalate metabolites and periodontitis. The generalized additive model and piecewise logistic regression were conducted to investigate the dose-response relationship. Cell and animal models were used to explore the role and mechanism of DEHP in the development of periodontitis. Transcriptome sequencing, bioinformatics analysis, western blot, immunofluorescence and mice model of periodontitis were also employed. RESULTS: MEHP (OR 1.14, 95% CI 1.05-1.24), MCPP (OR 1.08, 95% CI 1.00-1.17), MEHHP (OR 1.18, 95% CI 1.08-1.29), MEOHP (OR 1.18, 95% CI 1.07-1.29), MiBP (OR 1.15, 95% CI 1.04-1.28), and MECPP (OR 1.20, 95% CI 1.09-1.32) were independent risk factors. And MEHHP, the metabolite of DEHP, showed the relative most important effects on periodontitis with the highest weight (0.34) among all risk factors assessed. And the increase of inflammation and the activation of NFκB pathway in the periodontitis model mice and cells were observed. CONCLUSION: Exposure to multiple phthalates was positively associated with periodontitis in US adults between 30 and 80 years old. And DEHP aggravated inflammation in periodontitis by activating NFκB pathway.
Assuntos
Dietilexilftalato , Poluentes Ambientais , Periodontite , Ácidos Ftálicos , Adulto , Humanos , Animais , Camundongos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Exposição Ambiental/análise , Dietilexilftalato/metabolismo , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/metabolismo , Periodontite/induzido quimicamente , Inflamação , Poluentes Ambientais/análiseRESUMO
We aimed to characterize the association between air pollutants exposure and periodontal diseases outpatient visits and to explore the interactions between ambient air pollutants and meteorological factors. The outpatient visits data of several large stomatological and general hospitals in Hefei during 2015-2020 were collected to explore the relationship between daily air pollutants exposure and periodontal diseases by combining Poisson's generalized linear model (GLMs) and distributed lag nonlinear model (DLNMs). Subgroup analysis was performed to identify the vulnerability of different populations to air pollutants exposure. The interaction between air pollutants and meteorological factors was verified in both multiplicative and additive interaction models. An interquartile range (IQR) increased in nitrogen dioxide (NO2) concentration was associated with the greatest lag-specific relative risk (RR) of gingivitis at lag 3 days (RR = 1.087, 95% CI 1.008-1.173). Fine particulate matter (PM2.5) exposure also increased the risk of periodontitis at the day of exposure (RR = 1.049, 95% CI 1.004-1.096). Elderly patients with gingivitis and periodontitis were both vulnerable to PM2.5 exposure. The interaction analyses showed that exposure to high levels of NO2 at low temperatures was related to an increased risk of gingivitis, while exposure to high levels of NO2 and PM2.5 may also increase the risk of gingivitis and periodontitis in the high-humidity environment, respectively. This study supported that NO2 and PM2.5 exposure increased the risk of gingivitis and periodontitis outpatient visits, respectively. Besides, the adverse effects of air pollutants exposure on periodontal diseases may vary depending on ambient temperature and humidity.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Gengivite , Doenças Periodontais , Periodontite , Humanos , Idoso , Dióxido de Nitrogênio/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Material Particulado/análise , Conceitos Meteorológicos , Doenças Periodontais/etiologia , Doenças Periodontais/induzido quimicamente , Periodontite/induzido quimicamente , Gengivite/induzido quimicamente , Gengivite/epidemiologia , China , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análiseRESUMO
This joint report from the Italian Society of Orthopaedics and Traumatology (SIOT) and the Italian Society of Periodontology and Implantology (SIdP) aims for a consensus around the scientific rationale and clinical strategy for the management of osteoporotic patients affected by periodontitis who are undergoing anti-resorptive (AR) therapy to manage the risk of the occurrence of a medication-related osteonecrosis of the jaws (MRONJ). Osteoporosis and periodontitis are chronic diseases with a high prevalence in aging patients, and they share some of the same pathogenetic mechanisms based upon inflammation. Available evidence shows the relationship among osteoporosis, AR agents, periodontitis and implant therapy in relation to the incidence of MRONJ. Uncontrolled periodontitis may lead to tooth loss and to the need to replace teeth with dental implants. Tooth extraction and surgical dental procedures are recognized as the main risk factors for developing MRONJ in individuals taking AR therapy for osteometabolic conditions. Although the incidence of MRONJ in osteometabolic patients taking AR therapy may be as low as 0.9%, the increasing prevalence of osteoporosis and the high prevalence of periodontitis suggest that this potential complication should not be overlooked. Good clinical practice (GCP) guidelines are proposed that aim at a more integrated approach (prescriber, dentist, periodontist and dental hygienist) in the management of periodontitis patients undergoing AR therapy for osteometabolic disorders to reduce the risk of MRONJ. Dental professional and prescribers should educate patients regarding the potential risk associated with the long-term use of AR therapy and oral health behavior.
Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Ortopedia , Osteoporose , Periodontite , Traumatologia , Humanos , Conservadores da Densidade Óssea/uso terapêutico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Periodontite/complicações , Periodontite/terapia , Periodontite/induzido quimicamente , Osteoporose/complicações , Difosfonatos/efeitos adversosRESUMO
BACKGROUND AND PURPOSE: Low-grade inflammation, a common feature of both diabetes and periodontitis, partly accounts for the complexity and refractoriness of diabetes-associated periodontitis. Adiponectin (APN), the most abundant adipokine in human blood, has been widely reported to have anti-inflammatory functions. Herein, we investigated the ability of an APN receptor agonist, AdipoAI, to alleviate diabetes-associated periodontitis. Furthermore, we revealed the possible mechanism underlying its anti-inflammatory effects. EXPERIMENTAL APPROACH: The maxillary first molar of Zucker diabetic fatty (ZDF) rats was ligated to construct a diabetes-associated periodontitis model, and rats were administered AdipoAI by gavage. We examined diabetes-related indexes, pathological changes in insulin target organs, alveolar bone resorption and systemic and local inflammation. In vitro, transwell assays were used to evaluate monocyte/macrophage migration induced by human gingival fibroblasts (hGFs) with/without AdipoAI treatment. Additionally, we examined chemokine expression levels in hGFs and hGF-induced monocyte/macrophage migration upon siRNA knockdown of Adiponectin receptor expression. Expression of Adipo1/Adipo2 receptors and inflammation-related signalling pathways were examined by IHC and WB, followed by confirmation with an NF-κB P65 inhibitor (BAY 11-7082). KEY RESULTS: AdipoAI lowered fasting blood glucose and serum insulin in ZDF rats and alleviated inflammation in insulin target tissues. Locally, AdipoAI reduced alveolar bone absorption and gingival inflammation. Mechanistically, AdipoAI inhibited hGF-induced monocyte/macrophage migration by reducing CCL2 secretion. In hGFs, AdipoAI attenuated LPS-induced activation of NF-κB P65 and CCL2 expression, which was dependent on the Adipo receptor 1. CONCLUSION AND IMPLICATIONS: AdipoAI, with its ability to alleviate inflammatory damage in tissues, is a candidate for diabetes-associated periodontitis treatment.
Assuntos
Perda do Osso Alveolar , Diabetes Mellitus Experimental , Insulinas , Periodontite , Ratos , Humanos , Animais , Adiponectina/metabolismo , Receptores de Adiponectina/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , NF-kappa B/metabolismo , Ratos Zucker , Periodontite/tratamento farmacológico , Periodontite/induzido quimicamente , Periodontite/metabolismo , Inflamação/metabolismo , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/prevenção & controle , Perda do Osso Alveolar/metabolismo , Macrófagos/metabolismo , Fibroblastos/metabolismo , Insulinas/metabolismo , Lipopolissacarídeos/farmacologiaRESUMO
INTRODUCTION: Excessive lipoperoxidation is accompanied by accumulation of peroxidation products and depletion of antioxidant re-serves, which cause hyperenzymemia and the accumulation of toxic substances. The level of endotoxicosis is determined by the content of hydrophilic and hydrophobic products in the blood. AIM: To define the pathogenetic role of endogenous intoxication in the dynamics of development of experimental periodontitis of bacterial-immune genesis. MATERIALS AND METHODS: The experiment was conducted on rats. The animals were divided into three groups: group 1 - control group/intact; group 2 - model periodontitis at 7 days; group 3 - model periodontitis at 30 days. The experimental bacterial-immune periodon-titis was induced by injection into the tissue of the periodontal complex of the microorganisms' mixture diluted with egg's albumin. For the study, we selected the blood serum in which the content of middle molecular weight molecules and erythrocyte intoxication index were determined. The results were statistically analyzed by means of non-parametric indices methods. RESULTS: The development of generalized periodontitis is characterized by the occurrence of oxidative stress, which leads to violation of the metabolism in the mucous membrane of the oral cavity resulting in the accumulation of toxic products and the development of endogenous intoxication. The results show that the content of middle molecular weight molecules (aromatic amino and chain amino acids) determined on day 7 of the experiment was 1.11 times higher than that of the control group (p<0.01) and by 1.16 times (p<0.01), respectively. Comparing the levels of the above hydrophilic components of endogenous intoxication at 30 days of experimental peri-odontitis, we found a probable increase in these indicators compared with those at 7 days of the experiment. Studying the level of eryth-rocyte intoxication index, we found that at 7 days of experimental periodontitis this index was 1.28 times higher (p<0.01) than that of the intact group and continued to increase at 30 days. CONCLUSIONS: The dynamics of experimental periodontitis of bacterial-immune genesis show that the highest rates of endogenous intoxication are found in the late stages of the dynamics of the inflammatory process in the periodontium, namely at 30 days of the experiment, which may indicate chronic inflammation.
Assuntos
Antifibrinolíticos , Periodontite , Animais , Ratos , Periodontite/induzido quimicamente , Inflamação , PeriodontoRESUMO
Periodontitis is the most widespread oral disease and is closely related to the oral microbiota. The oral microbiota is adversely affected by some pharmacologic treatments. Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis, causing negative effects on the human body. Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed. In this research, mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss. The results demonstrated, for the first time, that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis. Moreover, the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue. Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier, decreased the pathogenicity of the oral microbiota, reversed the Th17/Treg imbalance in periodontal tissue, and alleviated alveolar bone loss. This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis. A Th17/Treg imbalance might be related to this relationship. Importantly, these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice.
Assuntos
Microbiota , Periodontite , Humanos , Camundongos , Animais , Disbiose , Antibacterianos/farmacologia , Virulência , Periodontite/induzido quimicamente , CitocinasRESUMO
STATEMENT OF PROBLEM: The outcome of implant-supported fixed complete dentures in edentulous patients with a history of periodontitis is unclear. PURPOSE: The purpose of this retrospective clinical study was to assess the clinical outcomes of immediate loaded fixed complete dentures in individuals with a history of periodontitis and to analyze risk factors related to implant failure. MATERIAL AND METHODS: A total of 642 implants (146 prostheses) in 119 patients were included. The follow-up period ranged from 2 to 7 years. Implant survival rates, marginal bone loss, mechanical complications, biologic complications, and patient satisfaction were evaluated. The Pearson chi-square test, independent samples t test, and multivariate generalized estimating equation were performed for statistical analysis (α=.05). RESULTS: Eleven implants in 9 patients failed, leading to overall survival rates of 98.3% at the implant level and 92.4% at the patient level. The mean ±standard deviation marginal bone loss was 0.62 ±0.86 mm, and marginal bone loss did not differ significantly between axial and tilted implants (P>.05). Mechanical complications were detected in 55 (37.7%) definitive prostheses; biologic complications were detected in 318 (49.5%) implants. Smokers had a significantly lower survival rate than nonsmokers (odds ratio: 6.880, P=.013). Bruxers had a significantly higher incidence of mechanical complications than nonbruxers (P<.001). CONCLUSIONS: The immediate loaded fixed complete denture supported by implants is a suitable treatment option for edentulous patients with a history of periodontitis, with high survival implant rates. Smoking is a risk factor for implant failure. Bruxism may increase the incidence of mechanical complications with implant-supported fixed complete dentures, and the overall biologic complication incidence is comparatively high.
Assuntos
Perda do Osso Alveolar , Produtos Biológicos , Implantes Dentários , Carga Imediata em Implante Dentário , Periodontite , Humanos , Implantes Dentários/efeitos adversos , Estudos Retrospectivos , Perda do Osso Alveolar/etiologia , Periodontite/induzido quimicamente , Periodontite/complicações , Prótese Total Imediata , Prótese Dentária Fixada por Implante/efeitos adversos , Seguimentos , Resultado do Tratamento , Falha de Restauração DentáriaRESUMO
Aim This study aimed to compare the long-term outcome of implant therapy in partially edentulous patients with severe periodontitis compared to those with no history of periodontitis.Design Retrospective cohort study.Cohort selection Eighty-eight patients (34 men and 54 women; age ranging from 28 to 45 years) with severe periodontitis (47 patients with 108 implants) and no history of periodontitis (41 patients with 78 implants) were included in this institutional study. All these cohorts had received implants 6-8 years previously.Data analysis Probing pocket depth, radiographic marginal bone level and peri-implantitis were the primary outcomes, while bleeding on probing was the secondary outcome. The effect of variables was measured by odds ratio with 95% confidence interval. Both patient-level and implant-level analyses were used to evaluate the association between peri-implantitis and potential risk factors. In addition, the association between probing pocket depth and radiographic marginal bone level with potential risk factors was assessed at implant-level analyses. In contrast, for patient-level data, a positive relationship was assessed with the Chi-square test.Results Patients with a history of severe periodontitis (OR = 11.13; p = 0.045), implants with a lack (<2 mm) of peri-implant keratinised mucosa (OR = 14.94; p <0.001) and implants placed in bone-grafted sites (OR = 4.93; p = 0.047) were associated with greater risk of peri-implantitis, at 6-8 years post-implant placement. The risk of developing radiographic marginal bone level ≥3 mm was significantly greater (OR = 1.20; p <0.001) in patients with higher full-mouth bleeding scores. The chance of peri-implant bleeding on probing was independently and especially higher in patients who brushed their teeth at most once per day (OR = 3.20; p = 0.04), with higher full-mouth bleeding score values (OR = 1.16; p <0.001) and irregular recall visits (OR = 15.34; p = 0.001).Conclusion This retrospective cohort study concluded that partially edentulous patients with a history of severe periodontitis were more prone to develop peri-implantitis at 6-8 years post-implant placement.
Assuntos
Perda do Osso Alveolar , Implantes Dentários , Boca Edêntula , Peri-Implantite , Periodontite , Adulto , Perda do Osso Alveolar/induzido quimicamente , Implantes Dentários/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Boca Edêntula/complicações , Peri-Implantite/induzido quimicamente , Peri-Implantite/complicações , Periodontite/induzido quimicamente , Periodontite/complicações , Estudos RetrospectivosRESUMO
PURPOSE: This study aimed to investigate the relationship between dental metal allergy, periodontitis, and palmoplantar pustulosis among patients from a dental metal allergy clinic over a period of 8 years. METHODS: This study included 436 patients who visited our dental metal allergy clinic between April 1, 2009 and March 31, 2016. Diagnoses of skin diseases, periodontal records, dental metal series patch test results, and electron probe microanalysis (EPMA) data were obtained from medical records. Relative risk (RR) values were estimated from these data. RESULTS: Of the 359 patients who underwent the patch test, 241 showed a positive reaction. Of the 187 patients who underwent EPMA, 113 had allergenic metals in their dental prostheses. These patients were suspected to have a dental metal allergy. Furthermore, 150 of the 436 patients were diagnosed with palmoplantar pustulosis (PPP). The RR of metal allergy between patients with PPP and healthy subjects was 3.88. The RR of periodontal disease between patients with PPP and PPP-negative patients in the national average was 2.54. CONCLUSION: In this study, both dental metal allergy and periodontitis showed a high RR for PPP.
Assuntos
Hipersensibilidade , Periodontite , Psoríase , Humanos , Metais/efeitos adversos , Testes do Emplastro , Periodontite/induzido quimicamente , Psoríase/induzido quimicamenteRESUMO
OBJECTIVE: The aim: To study the content of trace elements (cadmium and zinc) in the blood and oral fluid in people with generalized periodontitis and work and live permanently in adverse environmental conditions. PATIENTS AND METHODS: Materials and methods: In order to study the prevalence of periodontal diseases in adults living in areas with high level of soil contamination with heavy metal salts and working in the workplace with occupational hazards, there were studied 163 people who did not have somatic diseases, namely: 133 employees of Burshtyn Thermal Power Plant (TPP) and 30 persons who do not work at Burshtyn TPP. RESULTS: Results: The results of biochemical examination of blood and oral fluid in persons with generalized periodontitis of the I, II degree of severity and being exposed to adverse environmental factors, show changes in the trace element spectrum of blood and oral fluid, namely: a decrease in amount of zinc and an increase in amount of cadmium, which may indicate the disorder of microelement metabolism under conditions of chronic influence of small doses of salts of heavy metals. CONCLUSION: Conclusions: As a result of the performed study, a violation of micronutrient metabolism in biological fluids (blood and oral fluid) was found in persons exposed to adverse environmental factors.
Assuntos
Metais Pesados , Periodontite , Oligoelementos , Adulto , Cádmio , Humanos , Periodontite/induzido quimicamente , Periodontite/epidemiologia , ZincoRESUMO
Oral and gum health have long been associated with incidence and outcomes of cardiovascular disease. Periodontal disease increases myocardial infarction (MI) mortality by sevenfold through mechanisms that are not fully understood. The goal of this study was to evaluate whether lipopolysaccharide (LPS) from a periodontal pathogen accelerates inflammation after MI through memory T-cell activation. We compared four groups [no MI, chronic LPS, day 1 after MI, and day 1 after MI with chronic LPS (LPS + MI); n = 68 mice] using the mouse heart attack research tool 1.0 database and tissue bank coupled with new analyses and experiments. LPS + MI increased total CD8+ T cells in the left ventricle versus the other groups (P < 0.05 vs. all). Memory CD8+ T cells (CD44 + CD27+) were 10-fold greater in LPS + MI than in MI alone (P = 0.02). Interleukin (IL)-4 stimulated splenic CD8+ T cells away from an effector phenotype and toward a memory phenotype, inducing secretion of factors associated with the Wnt/ß-catenin signaling that promoted monocyte migration and decreased viability. To dissect the effect of CD8+ T cells after MI, we administered a major histocompatibility complex-I-blocking antibody starting 7 days before MI, which prevented effector CD8+ T-cell activation without affecting the memory response. The reduction in effector cells diminished infarct wall thinning but had no effect on macrophage numbers or MertK expression. LPS + MI + IgG attenuated macrophages within the infarct without effecting CD8+ T cells, suggesting these two processes were independent. Overall, our data indicate that effector and memory CD8+ T cells at post-MI day 1 are amplified by chronic LPS to potentially promote infarct wall thinning.NEW & NOTEWORTHY Although there is a well-documented link between periodontal disease and heart health, the mechanisms are unclear. Our study indicates that in response to circulating periodontal endotoxins, memory CD8+ T cells are activated, resulting in an acceleration of macrophage-mediated inflammation after MI. Blocking activation of effector CD8+ T cells had no effect on the macrophage numbers or wall thinning at post-MI day 1, indicating that this response was likely due in part to memory CD8+ T cells.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Memória Imunológica , Lipopolissacarídeos , Ativação Linfocitária , Infarto do Miocárdio/imunologia , Miocárdio/imunologia , Periodontite/imunologia , Porphyromonas gingivalis , Cicatrização , Animais , Linfócitos T CD8-Positivos/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Feminino , Mediadores da Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Periodontite/induzido quimicamente , Periodontite/metabolismo , Periodontite/patologia , Fagocitose , Fenótipo , Fatores de TempoRESUMO
Periodontitis is an inflammatory disease associated with severe alveolar bone loss and is dominantly induced by lipopolysaccharide from Gram-negative bacteria; however, the role of Gram-positive bacteria in periodontal bone resorption remains unclear. In this study, we examined the effects of lipoteichoic acid (LTA), a major cell-wall factor of Gram-positive bacteria, on the progression of inflammatory alveolar bone loss in a model of periodontitis. In coculture of mouse primary osteoblasts and bone marrow cells, LTA induced osteoclast differentiation in a dose-dependent manner. LTA enhanced the production of PGE2 accompanying the upregulation of the mRNA expression of mPGES-1, COX-2 and RANKL in osteoblasts. The addition of indomethacin effectively blocked the LTA-induced osteoclast differentiation by suppressing the production of PGE2. Using ex vivo organ cultures of mouse alveolar bone, we found that LTA induced alveolar bone resorption and that this was suppressed by indomethacin. In an experimental model of periodontitis, LTA was locally injected into the mouse lower gingiva, and we clearly detected alveolar bone destruction using 3D-µCT. We herein demonstrate a new concept indicating that Gram-positive bacteria in addition to Gram-negative bacteria are associated with the progression of periodontal bone loss.
Assuntos
Perda do Osso Alveolar/induzido quimicamente , Parede Celular/metabolismo , Bactérias Gram-Positivas/metabolismo , Inflamação/induzido quimicamente , Lipopolissacarídeos/farmacologia , Osteoblastos/efeitos dos fármacos , Prostaglandinas E/metabolismo , Ácidos Teicoicos/farmacologia , Perda do Osso Alveolar/metabolismo , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Inflamação/metabolismo , Masculino , Camundongos , Osteoblastos/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Periodontite/induzido quimicamente , Periodontite/metabolismo , Células RAW 264.7RESUMO
BACKGROUND: The aim of this study was to evaluate the role of AT1 and AT2 receptors in a periodontal inflammation experimental model. METHODS: Periodontal inflammation was induced by LPS/Porphyromonas gingivalis. Maxillae, femur, and vertebra were scanned using Micro-CT. Maxillae were analyzed histopathologically, immunohistochemically, and by RT-PCR. RESULTS: The vertebra showed decreased BMD in AT1 H compared with WT H (p < 0.05). The femur showed increased Tb.Sp for AT1 H and AT2 H, p < 0.01 and p < 0.05, respectively. The Tb.N was decreased in the vertebra (WT H-AT1 H: p < 0.05; WT H-AT2 H: p < 0.05) and in the femur (WT H-AT1 H: p < 0.01; WT H-AT2 H: p < 0.05). AT1 PD increased linear bone loss (p < 0.05) and decreased osteoblast cells (p < 0.05). RANKL immunostaining was intense for AT1 PD and WT PD (p < 0.001). OPG was intense in the WT H, WT PD, and AT2 PD when compared to AT1 PD (p < 0.001). AT1 PD showed weak immunostaining for osteocalcin compared with WT H, WT PD, and AT2 PD (p < 0.001). AT1 H showed significantly stronger immunostaining for osteonectin in fibroblasts compared to AT2 H (p < 0.01). CONCLUSION: AT1 receptor knockout changed bone density, the quality and number of bone trabeculae, decreased the number of osteoblast cells, and increased osteonectin in fibroblasts.
Assuntos
Densidade Óssea/genética , Periodontite/genética , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/genética , Animais , Modelos Animais de Doenças , Lipopolissacarídeos/toxicidade , Masculino , Camundongos Knockout , Óxido Nítrico Sintase Tipo II/genética , Periodontite/induzido quimicamente , Periodontite/diagnóstico por imagem , Periodontite/patologia , Porphyromonas gingivalis/patogenicidade , Ligante RANK/metabolismo , Microtomografia por Raio-XRESUMO
OBJECTIVE: To determine the crosstalk of osteogenesis and osteoclastogenesis of alveolar bone in lipopolysaccharide (LPS)-induced periodontitis in mice. METHODS: A representative periodontitis model was established by treating mice with LPS, and osteoblasts and osteoclasts were cultured. Osteoblasts and osteoclasts were cocultured to determine the effects of LPS on the crosstalk of osteogenesis and osteoclastogenesis. Quantitative polymerase chain reaction (qPCR) was performed to determine the expression of osteoclastogenesis makers underlying the potential mechanisms. RESULTS: The morphological and pathological changes in alveolar bone were observed in LPSinduced mice and LPS dose-dependently suppressed osteogenesis. The mRNA expression of cathepsin K, as a marker of osteoclasts, was accordingly downregulated in the coculture. The mRNA expression of osteoprotegerin was increased, while that of receptor activator of nuclear factor-κB ligand (RANKL) was decreased with an increased concentration of LPS. Moreover, the mRNA expression of toll-like receptor 4 (TLR4) was upregulated by LPS, whereas TLR4 knockout partially recovered osteoclast differentiation in the upper layer of the coculture. CONCLUSION: LPS dose-dependently suppressed osteogenesis but had a bidirectional effect on osteoclastogenesis. The combined effects of LPS on osteogenesis, osteoclastogenesis and their crosstalk via TLR4 account for alveolar bone loss in periodontitis.
Assuntos
Osteogênese , Periodontite , Animais , Lipopolissacarídeos , Camundongos , Osteoblastos , Osteoclastos , Osteogênese/genética , Periodontite/induzido quimicamente , Periodontite/genéticaRESUMO
Bacterial infection caused cell pyroptosis and gingival inflammation contributes to periodontitis progression, and lipopolysaccharide (LPS) is the main infectious agent of gram-negative bacteria, which is reported to be closely associated with gingival inflammation and periodontitis. In this study, the primary human periodontal ligament cells (PDLCs) were isolated, cultured, and exposed to LPS treatment, and the results suggested that LPS suppressed cell viability and promoted pro-inflammatory cytokines' (IL-1ß, IL-18, IL-6, and TNF-α) generation and secretion in the PDLCs and its supernatants in a time- and concentration-dependent manner. Also, we noticed that LPS upregulated NLRP3, Gasdermin D, and cleaved caspase-1 to trigger pyroptotic cell death in the PDLCs. Further experiments identified that glycogen synthase kinase-3ß (GSK-3ß) was upregulated by LPS treatment, and inhibition of GSK-3ß by its inhibitor (GSKI) or GSK-3ß downregulation vectors was effective to restore normal cellular functions in LPS-treated PDLCs. Mechanistically, blockage of GSK-3ß restrained NLRP3-meidated cell pyroptosis and inflammation, resulting in the recovery of cell viability and inhibition of cell death in PDLCs treated with LPS, which further ameliorated periodontitis progression. Finally, we collected the serum from periodontitis patients and healthy volunteers, and the clinical data supported that those pro-inflammatory cytokines were also upregulated in patients' serum but not in the healthy participants. Taken together, we concluded that targeting the GSK-3ß/NLRP3 pathway mediated cell pyroptosis was effective to attenuate LPS-induced cell death and inflammation in PDLCs, and this study firstly investigated this issue, which broadened our knowledge in this field.
Assuntos
Infecções Bacterianas/genética , Glicogênio Sintase Quinase 3 beta/genética , Interleucina-1beta/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Periodontite/genética , Infecções Bacterianas/induzido quimicamente , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Sobrevivência Celular/genética , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Gengiva/microbiologia , Gengiva/patologia , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/genética , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/patologia , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/toxicidade , Ligamento Periodontal/citologia , Ligamento Periodontal/microbiologia , Periodontite/induzido quimicamente , Periodontite/tratamento farmacológico , Periodontite/patologia , Cultura Primária de Células , Piroptose/efeitos dos fármacos , Piroptose/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genéticaRESUMO
It was hypothesized that periodontal diseases could be influenced by nutrition and food types. However, the role of nutritional factors in the risk of periodontal disease has not been clearly elucidated. This study was aimed at investigating the relationship between coffee, green tea, or soft drink intake and periodontitis. This prospective cohort study used epidemiological data from 2004 to 2016 from the Korean Genome and Epidemiology Study. Among 173,209 participants, 9,933 with periodontitis and 124,922 controls were selected. The frequency histories of coffee/green tea/soft drink intake among the participants were analyzed, and intake was categorized as no drink, mild drink (one time a month through six times a week), and heavy drink (one or more times a day). Variable factors were adjusted using logistic regression analysis (adjusted model). The chi-square test and independent t-test were used for statistical analysis. Adjusted odds ratio (aOR) for coffee or green tea intake and periodontitis were not statistically significant. The aOR was 1.16 (95% confidence interval (CI) = 1.11-1.21, P < 0.001) for mild soft drink intake and 1.02 (95%CI = 0.96-1.09, P = 0.518) for heavy soft drink intake. Subgroup analysis showed that mild soft drink intake was significant across all groups (P < 0.05), whereas coffee and green tea intakes were not significant in any subgroup. Overall, the study elucidated an association between mild soft drink intake and periodontitis.
Assuntos
Bebidas Gaseificadas/efeitos adversos , Café/efeitos adversos , Bases de Dados Factuais , Periodontite , Chá/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Periodontite/induzido quimicamente , Periodontite/epidemiologia , Estudos Prospectivos , Fatores de RiscoRESUMO
Periodontitis is usually sustained from microorganism of oral cavity, like Porphyromonas gingivalis (P. gingivalis). Periodontal disease is an infectious disease that afflicts a large number of people. Researches are investigating on the mesenchymal stem cells (MSCs) response to inflammatory events in combination with antioxidant substances. In particular, ascorbic acid (AA) increased cell proliferation, upregulated the cells pluripotency marker expression, provide a protection from inflammation, and induced the regeneration of periodontal ligament tissue. The purpose of the present research was to investigate the effects of AA in primary culture of human periodontal ligament stem cells (hPDLSCs) exposed to P. gingivalis lipopolysaccharide (LPS-G). The effect of AA on hPDLSCs exposed to LPS-G was determined through the cell proliferation assay. The molecules involved in the inflammatory pathway and epigenetic regulation have been identified using immunofluorescence and Western blot analyses. miR-210 level was quantified by qRT-PCR, and the ROS generation was finally studied. Cells co-treated with LPS-G and AA showed a restoration in terms of cell proliferation. The expression of NFκB, MyD88, and p300 was upregulated in LPS-G exposed cells, while the expression was attenuated in the co-treatment with AA. DNMT1 expression is attenuated in the cells exposed to the inflammatory stimulus. The level of miR-210 was reduced in stimulated cells, while the expression was evident in the hPDLSCs co-treated with LPS-G and AA. In conclusion, the AA could enhance a protective effect in in vitro periodontitis model, downregulating the inflammatory pathway and ROS generation and modulating the miR-210 level.
Assuntos
Ácido Ascórbico/farmacologia , Epigênese Genética/efeitos dos fármacos , Periodontite/genética , Células-Tronco/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Humanos , Lipopolissacarídeos/isolamento & purificação , Lipopolissacarídeos/farmacologia , Ligamento Periodontal/efeitos dos fármacos , Ligamento Periodontal/patologia , Ligamento Periodontal/fisiologia , Periodontite/induzido quimicamente , Periodontite/microbiologia , Periodontite/patologia , Porphyromonas gingivalis/química , Células-Tronco/patologia , Células-Tronco/fisiologiaRESUMO
Periodontitis is a widespread oral disease that results in the loss of alveolar bone. Low-intensity pulsed ultrasound (LIPUS), which is a new therapeutic option, promotes alveolar bone regeneration in periodontal bone injury models. This study investigated the protective effect of LIPUS on oxidative stress in periodontitis and the mechanism underlying this process. Methods: An experimental periodontitis model was induced by administering a ligature. Immunohistochemistry was performed to detect the expression levels of oxidative stress, osteogenic, and osteoclastogenic markers in vivo. Cell viability and osteogenic differentiation were analyzed using the Cell Counting Kit-8, alkaline phosphatase, and Alizarin Red staining assays. A reactive oxygen species assay kit, lipid peroxidation MDA assay kit, and western blotting were used to determine oxidative stress status in vitro. To verify the role of nuclear factor erythroid 2-related factor 2 (Nrf2), an oxidative regulator, during LIPUS treatment, the siRNA technique and Nrf2-/- mice were used. The PI3K/Akt inhibitor LY294002 was utilized to identify the effects of the PI3K-Akt/Nrf2 signaling pathway. Results: Alveolar bone resorption, which was experimentally induced by periodontitis in vivo, was alleviated by LIPUS via activation of Nrf2. Oxidative stress, induced via H2O2 treatment in vitro, inhibited cell viability and suppressed osteogenic differentiation. These effects were also alleviated by LIPUS treatment via Nrf2 activation. Nrf2 silencing blocked the antioxidant effect of LIPUS by diminishing heme oxygenase-1 expression. Nrf2-/- mice were susceptible to ligature-induced periodontitis, and the protective effect of LIPUS on alveolar bone dysfunction was weaker in these mice. Activation of Nrf2 by LIPUS was accompanied by activation of the PI3K/Akt pathway. The oxidative defense function of LIPUS was inhibited by exposure to LY294002 in vitro. Conclusions: These results demonstrated that LIPUS regulates alveolar bone homeostasis in periodontitis by attenuating oxidative stress via the regulation of PI3K-Akt/Nrf2 signaling. Thus, Nrf2 plays a pivotal role in the protective effect exerted by LIPUS against ligature-induced experimental periodontitis.
Assuntos
Osso e Ossos/metabolismo , Homeostase/fisiologia , Estresse Oxidativo/fisiologia , Periodontite/metabolismo , Animais , Antioxidantes/metabolismo , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/fisiologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Homeostase/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Periodontite/induzido quimicamente , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Ondas UltrassônicasRESUMO
BACKGROUND: Periodontitis is a multifactorial inflammatory disease of tooth supporting tissues caused by oral biofilms, influenced by environmental and genetic factors, among others. Ethanol consumption has been considered a factor that enhances alveolar bone loss, especially in high doses. The present study aims to investigate the changes promoted by ethanol binge drinking per se or associated with ligature-induced periodontal breakdown on alveolar bone loss. MATERIALS AND METHODS: Thirty-two Wistar rats were randomly allocated into four groups: control (C), ethanol (3g/kg/day; 3 days On-4 days Off protocol by gavage for 28 days, EtOH), experimental periodontitis (EP) and experimental periodontitis plus ethanol administration (EP+EtOH). On day 14th, periodontitis was induced by ligatures that were placed around the lower first molars. On day 28th, the animals were euthanized and mandibles were submitted to stereomicroscopy for exposed root area analysis and micro-computed tomography (micro-CT) for the evaluation of alveolar bone loss and microstructural parameters. RESULTS: The results revealed that ligature-induced alveolar bone loss is aggravated by ethanol binge drinking compared to controls (1.06 ± 0.10 vs 0.77 ± 0.04; p<0.0001). In addition, binge drinking per se altered the alveolar bone quality and density demonstrating a reduction in trabecular thickness, trabecular number parameter and bone density percentual. Periodontal disorder plus ethanol binge drinking group also demonstrated reduction of the quality of bone measured by trabecular thickness. CONCLUSIONS: In conclusion, intense and episodic ethanol intake decreased alveolar bone quality in all microstructural parameters analyzed which may be considered a modifying factor of periodontitis, intensifying the already installed disease.