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1.
Int J Mol Sci ; 22(19)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34638690

RESUMO

Periodontal inflammation is a common inflammatory disease associated with chronic inflammation that can ultimately lead to alveolar attachment loss and bone destruction. Understanding autophagy and pyroptosis has suggested their significant roles in inflammation. In recent years, studies of differentiated embryo-chondrocyte expressed genes 1 and 2 (Dec1 and Dec2) have shown that they play important functions in autophagy and in pyroptosis, which contribute to the onset of periodontal inflammation. In this review, we summarize recent studies on the roles of clock genes, including Dec1 and Dec2, that are related to periodontal inflammation and other diseases.


Assuntos
Autofagia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese , Regulação da Expressão Gênica , Proteínas de Homeodomínio/biossíntese , Periodontite/metabolismo , Piroptose , Animais , Humanos , Inflamação/metabolismo , Inflamação/patologia , Periodontite/patologia
2.
Am J Physiol Heart Circ Physiol ; 321(5): H948-H962, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34597184

RESUMO

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 Tempo
3.
Free Radic Biol Med ; 176: 298-311, 2021 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-34610362

RESUMO

Reactive oxygen species (ROS) overproduction promotes the alveolar bone loss during the development of periodontitis. Mitochondria are the principal source of ROS. Hydroxytyrosol (HT), a natural phenolic compound present in olive oil, is well known for its antioxidant and mitochondrial-protective prosperities. Nonetheless, the impact of HT on periodontitis and its related mechanisms underlying bone cell behavior remains unknown. Osteoclasts differentiated from RAW264.7 model and oxidative stress (OS) induced pre-osteoblast MC3T3-E1 cell injury model were treated with and without HT. Cell viability, apoptosis, differentiation, mitochondrial function along with mitogen-activated protein kinase (MAPK) signaling pathway were investigated. Meanwhile, the effect and related mechanisms of HT on bone loss in mice with periodontitis were also detected. HT inhibited osteoclast differentiation and prevented OS induced pre-osteoblast cells injury via regulating mitochondrial function as well as ERK and JNK signaling pathways. Moreover, HT attenuated the alveolar bone loss, increased bone forming activity, inhibited the osteoclasts differentiation and decreased the level of OS in mice with periodontitis. Our findings, for the first time, revealed a novel function of HT in bone remodeling of periodontitis, and highlighted its therapeutical potential for the prevention/treatment of periodontitis.


Assuntos
Proteínas Quinases Ativadas por Mitógeno , Periodontite , Animais , Diferenciação Celular , Sistema de Sinalização das MAP Quinases , Camundongos , Mitocôndrias/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Osteoblastos/metabolismo , Osteoclastos , Periodontite/tratamento farmacológico , Periodontite/metabolismo , Álcool Feniletílico/análogos & derivados , Transdução de Sinais
4.
Int J Mol Sci ; 22(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34502071

RESUMO

We evaluated the role of allicin in periodontitis using an in silico and in vitro design. An in silico docking analysis was performed to assess the plausible interactions between allicin and PD-L1. The cytokine profile of gingival crevicular fluid (GCF) samples obtained from periodontitis patients was estimated by cytometric bead array. CD3+ lymphocytes isolated from the peripheral blood were sorted and characterized using immunomagnetic techniques. Cultured and expanded lymphocytes were treated with the GCF samples to induce T-cell exhaustion. Optimum concentrations of allicin were added to exhausted lymphocytes to compare the expression of TIM-3 and LAG-3 gene expression at baseline and post-treatment. Allicin was found to bind to the PD-L1 molecule as revealed by the in-silico experiment, which is possibly an inhibitory interaction although not proven. GCF from periodontitis patients had significantly higher concentrations of TNF-α, CCL2, IL-6, IFN-γ, and CXCL8 than controls. GCF treatment of CD3+ lymphocytes from the periodontitis patients significantly increased expression of T-cell exhaustion markers TIM-3 and LAG-3. Allicin administration with GCF treatment resulted in significant lowering of the expression of exhaustion markers. Allicin may exert an immunostimulatory role and reverse immune-destructive mechanisms such as T-cell exhaustion.


Assuntos
Antígeno B7-H1/metabolismo , Dissulfetos/farmacologia , Periodontite/metabolismo , Ácidos Sulfínicos/farmacologia , Linfócitos T/efeitos dos fármacos , Antígenos CD/genética , Antígenos CD/metabolismo , Antígeno B7-H1/química , Sítios de Ligação , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocina CXCL6/genética , Quimiocina CXCL6/metabolismo , Dissulfetos/química , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Ligação Proteica , Ácidos Sulfínicos/química , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
5.
Biomed Res Int ; 2021: 3278351, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34532500

RESUMO

Recent studies have supported the relationship between periodontitis and carotid artery calcification (CAC), but still uncertain. This systematic review is aimed at evaluating the association between periodontitis and CAC. The search was conducted in four electronic databases: PubMed, EMBASE, Web of Science, and The Cochrane Library, supplemented by checking references of included articles and related review articles. Eligibility assessment and data extraction were conducted independently. The quality assessment and publication bias analysis were performed. The association between periodontitis and CAC was presented in odd ratio (OR) with 95% confidence interval (CI). Additional outcomes included the percentage of alveolar bone loss in CAC versus non-CAC. Twelve studies were included, and 10 were performed quantity analysis. Periodontitis with secure definition (OR = 2.02, 95%CI = 1.18 - 3.45) and insecure definition (OR = 10.78, 95%CI = 4.41 - 26.34) was associated with CAC. And a higher average percentage of alveolar bone loss (weighted mean difference = 10.84%; 95%CI = 6.40 - 15.48) was also observed in CAC patients compared to non-CAC patients. No significant publication bias was found. The results of this systematic review and meta-analysis revealed a significant relationship between periodontitis and CAC.


Assuntos
Calcinose/fisiopatologia , Artérias Carótidas/fisiopatologia , Artropatias/fisiopatologia , Periodontite/fisiopatologia , Doenças Vasculares/fisiopatologia , Artérias Carótidas/metabolismo , Doenças das Artérias Carótidas/fisiopatologia , Doença da Artéria Coronariana/fisiopatologia , Humanos , Razão de Chances , Periodontite/metabolismo , Medição de Risco/métodos , Fatores de Risco
6.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208697

RESUMO

Traditional antimicrobial therapies for periodontitis (PD) have long focused on non-selective and direct approaches. Professional cleaning of the subgingival biofilm by instrumentation of dental root surfaces, known as scaling and root planning (SRP), is the mainstay of periodontal therapy and is indisputably effective. Non-physical approaches used as adjuncts to SRP, such as chemical and biological agents, will be the focus of this review. In this regard, traditional agents such as oral antiseptics and antibiotics, delivered either locally or systemically, were briefly reviewed as a backdrop. While generally effective in winning the "battle" against PD in the short term, by reducing its signs and symptoms, patients receiving such therapies are more susceptible to recurrence of PD. Moreover, the long-term consequences of such therapies are still in question. In particular, concern about chronic use of systemic antibiotics and their influence on the oral and gut microbiota is warranted, considering antibiotic resistance plasmids, and potential transfer between oral and non-oral microbes. In the interest of winning the "battle and the war", new more selective and targeted antimicrobials and biologics for PD are being studied. These are principally indirect, blocking pathways involved in bacterial colonization, nutrient acquisition, inflammation or cellular invasion without directly killing the pathogens. This review will focus on current and prospective antimicrobial therapies for PD, emphasizing therapies that act indirectly on the microbiota, with clearly defined cellular and molecular targets.


Assuntos
Antibacterianos/uso terapêutico , Periodontite/tratamento farmacológico , Periodontite/microbiologia , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Terapia Combinada , Gerenciamento Clínico , Suscetibilidade a Doenças , Vias de Administração de Medicamentos , Humanos , Periodontite/metabolismo , Resultado do Tratamento
7.
Genes (Basel) ; 12(5)2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065604

RESUMO

The clinical interaction between stroke and periodontitis has been consistently studied and confirmed. Hence, exploring potentially new protein interactions in this association using bioinformatic strategies presents potential interest. In this exploratory study, we conducted a protein-protein network interaction (PPI) search with documented encoded proteins for both stroke and periodontitis. Genes of interest were collected via GWAS database. The STRING database was used to predict the PPI networks, first in a sensitivity purpose (confidence cut-off of 0.7), and then with a highest confidence cut-off (0.9). Genes over-representation was inspected in the final network. As a result, we foresee a prospective protein network of interaction between stroke and periodontitis. Inflammation, pro-coagulant/pro-thrombotic state and, ultimately, atheroma plaque rupture is the main biological mechanism derived from the network. These pilot results may pave the way to future molecular and therapeutic studies to further comprehend the mechanisms between these two conditions.


Assuntos
Periodontite/genética , Mapas de Interação de Proteínas , Acidente Vascular Cerebral/genética , Redes Reguladoras de Genes , Periodontite/metabolismo , Acidente Vascular Cerebral/metabolismo
8.
PLoS One ; 16(6): e0252859, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34153036

RESUMO

Patients with rheumatoid arthritis (RA) experience a higher prevalence of periodontitis. This study aimed to examine the variation of periodontitis experienced with different serotypes suffered by RA patients and to examine the relationship between the different medications taken for RA that may influence this relationship. Two hundred and sixty RA and control participants underwent standardized periodontal examinations. Medical, serological and radiological (Sharp/van der Heijde) records were assessed. Functional status was assessed using the administered Health Assessment Questionnaire. Moreover, disease parameters, including disease activity (DAS28-ESR) and anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) seropositivity were evaluated. Periodontitis was higher in RA (71.54%) compared with controls (54.62%). The stage of periodontitis experienced by ACPA-positive participants were higher than APCA-negative participants. The probing pocket depth and recession experienced by RF-positive participants were higher than those who were RF-negative. RA participants on methotrexate had lower clinical attachment loss and lower periodontal probing depth compared with participants on a combination methotrexate and other disease-modifying antirheumatic drugs. Participants taking corticosteroids had lower gingival index scores. The association between seropositivity and the type of medications taken with periodontal health parameters in this group of patients suggests that both seropositivity and medications taken are important modifiers in the relationship between periodontitis and RA.


Assuntos
Anticorpos Anti-Proteína Citrulinada/metabolismo , Antirreumáticos/farmacologia , Artrite Reumatoide/fisiopatologia , Osteoartrite/fisiopatologia , Periodontite/epidemiologia , Sorogrupo , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Estudos de Casos e Controles , Feminino , Humanos , Malásia/epidemiologia , Masculino , Metotrexato/farmacologia , Pessoa de Meia-Idade , Osteoartrite/sangue , Osteoartrite/tratamento farmacológico , Periodontite/metabolismo , Periodontite/patologia
9.
Sci Rep ; 11(1): 13353, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172796

RESUMO

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 264.7
10.
Front Immunol ; 12: 691216, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177951

RESUMO

Failure of resolution pathways in periodontitis is reflected in levels of specialized pro-resolving lipid mediators (SPMs) and SPM pathway markers but their relationship with the subgingival microbiome is unclear. This study aimed to analyze and integrate lipid mediator level, SPM receptor gene expression and subgingival microbiome data in subjects with periodontitis vs. healthy controls. The study included 13 periodontally healthy and 15 periodontitis subjects that were evaluated prior to or after non-surgical periodontal therapy. Samples of gingival tissue and subgingival plaque were collected prior to and 8 weeks after non-surgical treatment; only once in the healthy group. Metabololipidomic analysis was performed to measure levels of SPMs and other relevant lipid mediators in gingiva. qRT-PCR assessed relative gene expression (2-ΔΔCT) of known SPM receptors. 16S rRNA sequencing evaluated the relative abundance of bacterial species in subgingival plaque. Correlations between lipid mediator levels, receptor gene expression and bacterial abundance were analyzed using the Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) and Sparse Partial Least Squares (SPLS) methods. Profiles of lipid mediators, receptor genes and the subgingival microbiome were distinct in the three groups. The strongest correlation existed between lipid mediator profile and subgingival microbiome profile. Multiple lipid mediators and bacterial species were highly correlated (correlation coefficient ≥0.6) in different periodontal conditions. Comparing individual correlated lipid mediators and bacterial species in periodontitis before treatment to healthy controls revealed that one bacterial species, Corynebacterium durum, and five lipid mediators, 5(S)6(R)-DiHETE, 15(S)-HEPE, 7-HDHA, 13-HDHA and 14-HDHA, were identified in both conditions. Comparing individual correlated lipid mediators and bacterial species in periodontitis before treatment to after treatment revealed that one bacterial species, Anaeroglobus geminatus, and four lipid mediators, 5(S)12(S)-DiHETE, RvD1, Maresin 1 and LTB4, were identified in both conditions. Four Selenomonas species were highly correlated with RvD1, RvE3, 5(S)12(S)-DiHETE and proinflammatory mediators in the periodontitis after treatment group. Profiles of lipid mediators, receptor gene and subgingival microbiome are associated with periodontal inflammation and correlated with each other, suggesting inflammation mediated by lipid mediators influences microbial composition in periodontitis. The role of correlated individual lipid mediators and bacterial species in periodontal inflammation have to be further studied.


Assuntos
Gengiva/metabolismo , Gengiva/microbiologia , Metabolismo dos Lipídeos , Metaboloma , Microbiota , Periodontite/metabolismo , Periodontite/microbiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Bactérias/genética , Feminino , Humanos , Lipídeos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Receptores de Quimiocinas/genética , Receptores Acoplados a Proteínas G/genética , Receptores do Leucotrieno B4/genética , Adulto Jovem
11.
Front Immunol ; 12: 664756, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34012448

RESUMO

Periodontitis is a chronic inflammatory disease associated with the formation of dysbiotic plaque biofilms and characterized by the progressive destruction of the alveolar bone. The transition from health to disease is characterized by a shift in periodontal immune cell composition, from mostly innate (neutrophils) to adaptive (T lymphocytes) immune responses. Resolvin E1 (RvE1) is a specialized pro-resolution mediator (SPMs), produced in response to inflammation, to enhance its resolution. Previous studies have indicated the therapeutic potential of RvE1 in periodontal disease; however, the impact of RvE1 in the microbial-elicited osteoclastogenic immune response remains uncharacterized in vivo. In the present study, we studied the impact of RvE1 on the gingival inflammatory infiltrate formation during periodontitis in a mouse model. First, we characterized the temporal-dependent changes of the main immune cells infiltrating the gingiva by flow cytometry. Then, we evaluated the impact of early or delayed RvE1 administration on the gingival immune infiltration and cervical lymph nodes composition. We observed a consistent inhibitory outcome on T cells -particularly effector T cells- and a protective effect on regulatory T cells (Tregs). Our data further demonstrated the wide range of actions of RvE1, its preventive role in the establishment of the adaptive immune response during inflammation, and bone protective capacity.


Assuntos
Ácido Eicosapentaenoico/análogos & derivados , Gengivite/etiologia , Gengivite/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Perda do Osso Alveolar/etiologia , Perda do Osso Alveolar/metabolismo , Perda do Osso Alveolar/patologia , Animais , Modelos Animais de Doenças , Progressão da Doença , Ácido Eicosapentaenoico/farmacologia , Gengivite/tratamento farmacológico , Gengivite/patologia , Imunofenotipagem , Linfonodos/imunologia , Linfonodos/metabolismo , Linfonodos/patologia , Camundongos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Periodontite/etiologia , Periodontite/metabolismo , Periodontite/patologia , Linfócitos T/patologia
12.
Int J Mol Sci ; 22(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807391

RESUMO

Salivary levels of interleukin-8 (IL-8) are elevated in patients with periodontitis. Caffeic acid phenethyl ester (CAPE) improves the periodontal status in subjects. However, whether CAPE can reduce IL-8 expression is unclear. We collected saliva to determine proinflammatory cytokine levels and used subgingival calculus and surrounding tissues from patients with periodontitis for oral microbiota analysis via 16s ribosomal RNA gene sequencing. THP-1 cells were stimulated with sterile-filtered saliva from patients, and target gene/protein expression was assessed. IL-8 mRNA expression was analyzed in saliva-stimulated THP-1 cells treated with CAPE and the heme oxygenase-1 (HO-1) inhibitor tin-protoporphyrin (SnPP). In 72 symptomatic individuals, IL-8 was correlated with periodontal inflammation (bleeding on probing, r = 0.45; p < 0.001) and disease severity (bleeding on probing, r = 0.45; p < 0.001) but not with the four oral microbiota species tested. Reduced salivary IL-8 secretion was correlated with effective periodontitis treatment (r = 0.37, p = 0.0013). In THP-1 cells, saliva treatment induced high IL-8 expression and IKK2 and nuclear factor-κB (NF-κB) phosphorylation. However, the IKK inhibitor BMS-345541, NF-κB inhibitor BAY 11-7082, and CAPE attenuated saliva-induced IL-8 expression. CAPE induced HO-1 expression and inhibited IKK2, IκBα, and NF-κB phosphorylation. Blocking HO-1 decreased the anti-inflammatory activity of CAPE. The targeted suppression of IL-8 production using CAPE reduces inflammation and periodontitis.


Assuntos
Ácidos Cafeicos/farmacologia , Interleucina-8/metabolismo , Periodontite/tratamento farmacológico , Álcool Feniletílico/análogos & derivados , Anti-Inflamatórios/farmacologia , Ácidos Cafeicos/metabolismo , Citocinas/metabolismo , Heme Oxigenase-1/metabolismo , Humanos , Proteínas I-kappa B/metabolismo , Inflamação/tratamento farmacológico , Interleucina-8/antagonistas & inibidores , Lipopolissacarídeos/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Periodontite/imunologia , Periodontite/metabolismo , Álcool Feniletílico/metabolismo , Álcool Feniletílico/farmacologia , Fosforilação/efeitos dos fármacos , Saliva/química , Células THP-1
13.
Int J Mol Sci ; 22(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803323

RESUMO

Periodontitis is the inflammatory destruction of the tooth-surrounding and -supporting tissue, resulting at worst in tooth loss. Another locally aggressive disease of the oral cavity is tooth resorption (TR). This is associated with the destruction of the dental mineralized tissue. However, the underlying pathomechanisms remain unknown. The complement system, as well as mast cells (MCs), are known to be involved in osteoclastogenesis and bone loss. The complement factors C3 and C5 were previously identified as key players in periodontal disease. Therefore, we hypothesize that complement factors and MCs might play a role in alveolar bone and tooth resorption. To investigate this, we used the cat as a model because of the naturally occurring high prevalence of both these disorders in this species. Teeth, gingiva samples and serum were collected from domestic cats, which had an appointment for dental treatment under anesthesia, as well as from healthy cats. Histological analyses, immunohistochemical staining and the CH-50 and AH-50 assays revealed increased numbers of osteoclasts and MCs, as well as complement activity in cats with TR. Calcifications score in the gingiva was highest in animals that suffer from TR. This indicates that MCs and the complement system are involved in the destruction of the mineralized tissue in this condition.


Assuntos
Perda do Osso Alveolar/metabolismo , Complemento C3/metabolismo , Complemento C5/metabolismo , Mastócitos/metabolismo , Periodontite/metabolismo , Reabsorção de Dente/metabolismo , Perda do Osso Alveolar/patologia , Animais , Gatos , Mastócitos/patologia , Osteoclastos/metabolismo , Osteoclastos/patologia , Periodontite/patologia , Reabsorção de Dente/patologia
14.
Int J Mol Sci ; 22(9)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33924932

RESUMO

Periodontitis is a chronic complex inflammatory disease associated with a destructive host immune response to microbial dysbiosis, leading to irreversible loss of tooth-supporting tissues. Regeneration of functional periodontal soft (periodontal ligament and gingiva) and hard tissue components (cementum and alveolar bone) to replace lost tissues is the ultimate goal of periodontal treatment, but clinically predictable treatments are lacking. Similarly, the identification of biomarkers that can be used to accurately diagnose periodontitis activity is lacking. A relatively novel category of molecules found in oral tissue, circular RNAs (circRNAs) are single-stranded endogenous, long, non-coding RNA molecules, with covalently circular-closed structures without a 5' cap and a 3' tail via non-classic backsplicing. Emerging research indicates that circRNAs are tissue and disease-specific expressed and have crucial regulatory functions in various diseases. CircRNAs can function as microRNA or RNA binding sites or can regulate mRNA. In this review, we explore the biogenesis and function of circRNAs in the context of the emerging role of circRNAs in periodontitis pathogenesis and the differentiation of periodontal cells. CircMAP3K11, circCDK8, circCDR1as, circ_0062491, and circ_0095812 are associated with pathological periodontitis tissues. Furthermore, circRNAs are expressed in periodontal cells in a cell-specific manner. They can function as microRNA sponges and can form circRNA-miRNA-mRNA networks during osteogenic differentiation for periodontal-tissue (or dental pulp)-derived progenitor cells.


Assuntos
Periodontite/metabolismo , Periodonto/metabolismo , RNA Circular/metabolismo , Regeneração , Animais , Humanos
15.
Int J Mol Sci ; 22(9)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33925019

RESUMO

Periodontitis is considered a promoter of many systemic diseases, but the signaling pathways of this interconnection remain elusive. Recently, it became evident that certain microbial challenges promote a heightened response of myeloid cell populations to subsequent infections either with the same or other pathogens. This phenomenon involves changes in the cell epigenetic and transcription, and is referred to as ''trained immunity''. It acts via modulation of hematopoietic stem and progenitor cells (HSPCs). A main modulation driver is the sustained, persistent low-level transmission of lipopolysaccharide from the periodontal pocket into the peripheral blood. Subsequently, the neutrophil phenotype changes and neutrophils become hyper-responsive and prone to boosted formation of neutrophil extracellular traps (NET). Cytotoxic neutrophil proteases and histones are responsible for ulcer formations on the pocket epithelium, which foster bacteremia and endoxemia. The latter promote systemic low-grade inflammation (SLGI), a precondition for many systemic diseases and some of them, e.g., atherosclerosis, diabetes etc., can be triggered by SLGI alone. Either reverting the polarized neutrophils back to the homeostatic state or attenuation of neutrophil hyper-responsiveness in periodontitis might be an approach to diminish or even to prevent systemic diseases.


Assuntos
Doença/etiologia , Endotoxemia/imunologia , Neutrófilos/fisiologia , Periodontite/complicações , Animais , Endotoxemia/metabolismo , Humanos , Lipopolissacarídeos/metabolismo , Periodontite/imunologia , Periodontite/metabolismo
16.
Sci Rep ; 11(1): 9282, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33927312

RESUMO

We used a nonhuman primate model of ligature-induced periodontitis to identify patterns of gingival transcriptomic after changes demarcating phases of periodontitis lesions (initiation, progression, resolution). A total of 18 adult Macaca mulatta (12-22 years) had ligatures placed (premolar, 1st molar teeth) in all 4 quadrants. Gingival tissue samples were obtained (baseline, 2 weeks, 1 and 3 months during periodontitis and at 5 months resolution). Gene expression was analyzed by microarray [Rhesus Gene 1.0 ST Array (Affymetrix)]. Compared to baseline, a large array of genes were significantly altered at initiation (n = 6049), early progression (n = 4893), and late progression (n = 5078) of disease, with the preponderance being up-regulated. Additionally, 1918 genes were altered in expression with disease resolution, skewed towards down-regulation. Assessment of the genes demonstrated specific profiles of epithelial, bone/connective tissue, apoptosis/autophagy, metabolism, regulatory, immune, and inflammatory responses that were related to health, stages of disease, and tissues with resolved lesions. Unique transcriptomic profiles occured during the kinetics of the periodontitis lesion exacerbation and remission. We delineated phase specific gene expression profiles of the disease lesion. Detection of these gene products in gingival crevicular fluid samples from human disease may contribute to a better understanding of the biological dynamics of the disease to improve patient management.


Assuntos
Gengiva/metabolismo , Periodontite/genética , Transcriptoma , Animais , Modelos Animais de Doenças , Progressão da Doença , Regulação da Expressão Gênica , Líquido do Sulco Gengival/metabolismo , Humanos , Macaca mulatta , Periodontite/metabolismo
17.
Front Immunol ; 12: 591236, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841392

RESUMO

Systemic lupus erythematosus (SLE) is a complex chronic autoimmune disease characterized by tissue damage and widespread inflammation in response to environmental challenges. Deposition of immune complexes in kidneys glomeruli are associated with lupus nephritis, determining SLE diagnosis. Periodontitis is a chronic inflammatory disease characterized by clinical attachment and bone loss, caused by a microbial challenge - host response interaction. Deposition of immune complex at gingival tissues is a common finding in the course of the disease. Considering that, the primary aim of this study is to investigate the deposition of immune complexes at gingival tissues of SLE patients compared to systemically healthy ones, correlating it to periodontal and systemic parameters. Twenty-five women diagnosed with SLE (SLE+) and 25 age-matched systemically healthy (SLE-) women were included in the study. Detailed information on overall patient's health were obtained from file records. Participants were screened for probing depth (PD), clinical attachment loss (CAL), gingival recession (REC), full-mouth bleeding score (FMBS) and plaque scores (FMPS). Bone loss was determined at panoramic X-ray images as the distance from cementenamel junction to alveolar crest (CEJ-AC). Gingival biopsies were obtained from the first 15 patients submitted to surgical periodontal therapy of each group, and were analyzed by optical microscopy and direct immunofluorescence to investigate the deposition of antigen-antibody complexes. Eleven (44%) patients were diagnosed with active SLE (SLE-A) and 14 (56%) with inactive SLE (LES-I). Mean PD, CAL and FMBS were significantly lower in SLE+ than SLE-(p < 0.05; Mann Whitney). The chronic use of low doses of immunosuppressants was associated with lower prevalence of CAL >3 mm. Immunofluorescence staining of markers of lupus nephritis and/or proteinuria was significantly increased in SLE+ compared to SLE-, even in the presence of periodontitis. These findings suggest that immunomodulatory drugs in SLE improves periodontal parameters. The greater deposition of antigen-antibody complexes in the gingival tissues of patients diagnosed with SLE may be a marker of disease activity, possibly complementing their diagnosis.


Assuntos
Complexo Antígeno-Anticorpo/imunologia , Suscetibilidade a Doenças , Gengiva/imunologia , Lúpus Eritematoso Sistêmico/etiologia , Periodontite/etiologia , Adulto , Complexo Antígeno-Anticorpo/metabolismo , Biomarcadores , Comorbidade , Gerenciamento Clínico , Feminino , Imunofluorescência , Humanos , Imuno-Histoquímica , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , Pessoa de Meia-Idade , Periodontite/diagnóstico , Periodontite/epidemiologia , Periodontite/metabolismo , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
18.
Int J Mol Sci ; 22(5)2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673616

RESUMO

BACKGROUND: Periodontitis is a chronic disease with a complex etiology that includes bacterial colonization, excessive inflammation, and oxidative stress. The hormone melatonin has antioxidant properties and might contribute to alleviating chronic conditions by reducing oxidative stress. The aim of this study was to analyze the effect of exogenous melatonin on periodontitis in an animal model of the disease as well as in patients with periodontitis. METHODS: In rats with ligature-induced periodontitis, melatonin was administered in drinking water for two weeks. In the human study, patients with treatment-resistant periodontitis were asked to rinse their mouths with a solution containing melatonin or placebo every evening for two weeks. Periodontal status as well as salivary markers of oxidative stress were assessed at the end of the study. RESULTS: Neither radiography nor µCT revealed any significant effects of melatonin on alveolar bone loss. Gum recession was the only improved macroscopic measure in rats (p < 0.05). Analysis of salivary markers of oxidative stress revealed no effects of treatment in rats or humans despite clearly elevated melatonin concentrations in melatonin treated groups. CONCLUSION: Our results do not support the use of melatonin for the treatment of periodontitis. However, the negative outcome is limited by the short duration of the study and the chosen route of application as well as the dose of melatonin.


Assuntos
Antioxidantes/farmacologia , Modelos Animais de Doenças , Inflamação/prevenção & controle , Melatonina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Periodontite/tratamento farmacológico , Saliva/metabolismo , Animais , Biomarcadores/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Periodontite/metabolismo , Periodontite/patologia , Ratos , Ratos Wistar , Saliva/efeitos dos fármacos
19.
Int J Mol Sci ; 22(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33670900

RESUMO

Periodontitis is an inflammatory disease, associated with a microbial dysbiosis. Early detection using salivary small extracellular vesicles (sEVs) biomarkers may facilitate timely prevention. sEVs derived from different species (i.e., humans, bacteria) are expected to circulate in saliva. This pilot study recruited 22 participants (seven periodontal healthy, seven gingivitis and eight periodontitis) and salivary sEVs were isolated using the size-exclusion chromatography (SEC) method. The healthy, gingivitis and periodontitis groups were compared in terms of salivary sEVs in the CD9+ sEV subpopulation, Gram-negative bacteria-enriched lipopolysaccharide (LPS+) outer membrane vesicles (OMVs) and global DNA methylation pattern of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) and N6-Methyladenosine (m6dA). It was found that LPS+ OMVs, global 5mC methylation and four periodontal pathogens (T. denticola, E. corrodens, P. gingivalis and F. nucleatum) that secreted OMVs were significantly increased in periodontitis sEVs compared to those from healthy groups. These differences were more pronounced in sEVs than the whole saliva and were more superior in distinguishing periodontitis than gingivitis, in comparison to healthy patients. Of note, global 5mC hypermethylation in salivary sEVs can distinguish periodontitis patients from both healthy controls and gingivitis patients with high sensitivity and specificity (AUC = 1). The research findings suggest that assessing global sEV methylation may be a useful biomarker for periodontitis.


Assuntos
Membrana Externa Bacteriana , Biomarcadores/análise , Metilação de DNA , Vesículas Extracelulares , Gengivite/diagnóstico , Periodontite/diagnóstico , Saliva/metabolismo , Adulto , Idoso , Eikenella corrodens , Feminino , Fusobacterium nucleatum , Gengivite/metabolismo , Gengivite/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Periodontite/metabolismo , Periodontite/microbiologia , Projetos Piloto , Porphyromonas gingivalis , Saliva/química , Treponema denticola , Adulto Jovem
20.
Cell Prolif ; 54(5): e13026, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33759282

RESUMO

OBJECTIVES: Previously, our investigations demonstrated robust pro-angiogenic potentials of extracellular vesicles secreted by periodontitis-compromised dental pulp stem cells (P-EVs) when compared to those from healthy DPSCs (H-EVs), but the underlying mechanism remains unknown. MATERIALS AND METHODS: Here, circulating microRNAs (miRNAs) specifically found in P-EVs (compared with H-EVs) were identified by Agilent miRNA microarray analysis, and the roles of the candidate miRNA in P-EV-enhanced cell angiogenesis were confirmed by cell transfection and RNA interference methods. Next, the direct binding affinity between the candidate miRNA and its target gene was evaluated by luciferase reporter assay. CCK-8, transwell/scratch wound healing and tube formation assays were established to investigate the proliferation, migration, and tube formation abilities of endothelial cells (ECs). Western blot was employed to measure the protein levels of Hedgehog/Gli1 signalling pathway components and angiogenesis-related factors. RESULTS: The angiogenesis-related miRNA miR-378a was found to be enriched in P-EVs, and its role in P-EV-enhanced cell angiogenesis was confirmed, wherein Sufu was identified as a downstream target gene of miR-378a. Functionally, silencing of Sufu stimulated EC proliferation, migration and tube formation by activating Hedgehog/Gli1 signalling. Further, we found that incubation with P-EVs enabled the transmission of P-EV-contained miR-378a to ECs. Subsequently, the expressions of Sufu, Gli1 and vascular endothelial growth factor in ECs were significantly influenced by P-EV-mediated miR-378a transmission. CONCLUSIONS: These data suggest that P-EVs carrying miR-378a promote EC angiogenesis by downregulating Sufu to activate the Hedgehog/Gli1 signalling pathway. Our findings reveal a crucial role for EV-derived miR-378a in cell angiogenesis and hence offer a new target for modifying stem cells and their secreted EVs to enhance vessel regenerative potential.


Assuntos
Vesículas Extracelulares/metabolismo , MicroRNAs/metabolismo , Neovascularização Fisiológica , Proteínas Repressoras/metabolismo , Transdução de Sinais , Antagomirs/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Polpa Dentária/citologia , Polpa Dentária/metabolismo , Vesículas Extracelulares/genética , Proteínas Hedgehog/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Periodontite/metabolismo , Periodontite/patologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/genética , Células-Tronco/citologia , Células-Tronco/metabolismo , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismo
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