RESUMO
During periodontitis, the extracellular capsule of Porphyromonas gingivalis favors alveolar bone loss by inducing Th1 and Th17 patterns of lymphocyte response in the infected periodontium. Dendritic cells recognize bacterial antigens and present them to T lymphocytes, defining their activation and polarization. Thus, dendritic cells could be involved in the Th1 and Th17 response induced against the P. gingivalis capsule. Herein, monocyte-derived dendritic cells were obtained from healthy individuals and then stimulated with different encapsulated strains of P. gingivalis or two non-encapsulated isogenic mutants. Dendritic cell differentiation and maturation were analyzed by flow cytometry. The mRNA expression levels for distinct Th1-, Th17-, or T-regulatory-related cytokines and transcription factors, as well as TLR2 and TLR4, were assessed by qPCR. In addition, the production of IL-1ß, IL-6, IL-23, and TNF-α was analyzed by ELISA. The encapsulated strains and non-encapsulated mutants of P. gingivalis induced dendritic cell maturation to a similar extent; however, the pattern of dendritic cell response was different. In particular, the encapsulated strains of P. gingivalis induced higher expression of IRF4 and NOTCH2 and production of IL-1ß, IL-6, IL-23, and TNF-α compared with the non-encapsulated mutants, and thus, they showed an increased capacity to trigger Th1 and Th17-type responses in human dendritic cells.
Assuntos
Citocinas , Células Dendríticas , Porphyromonas gingivalis , Células Th17 , Receptor 2 Toll-Like , Receptor 4 Toll-Like , Porphyromonas gingivalis/imunologia , Humanos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/microbiologia , Células Th17/imunologia , Células Th17/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Citocinas/metabolismo , Diferenciação Celular , Células Th1/imunologia , Fatores Reguladores de Interferon/metabolismo , Fatores Reguladores de Interferon/genética , Receptor Notch2/genética , Receptor Notch2/metabolismo , Células Cultivadas , Cápsulas Bacterianas/imunologia , Cápsulas Bacterianas/metabolismo , Infecções por Bacteroidaceae/imunologia , Infecções por Bacteroidaceae/microbiologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: There is no clear understanding of molecular events occurring in the periodontal microenvironment during clinical disease progression. Our aim was to explore qualitative and quantitative differences in gingival crevicular fluid (GCF) protein profiles from patients diagnosed with periodontitis between non-progressive and progressive periodontal sites. METHODS: Five systemically healthy patients diagnosed with periodontitis were monitored weekly in their progression of the disease and GCF samples from 10 candidate sites were obtained. Two groups of five sites, matched from an equal number of teeth, were selected from the five patients: Progression (PG) and Non-Progression (NP). Global protein identification was performed with high-throughput proteomic approaches and label-free analysis determined their relative abundances. Proteins were identified by Proteome Discoverer v2.4 and searched against human SwissProt protein databases. Enrichment bioinformatic analyses were performed in STRING-DB and ShinyGO environment. RESULTS: 1504 and 1500 proteins were identified in NP and PG respectively. Forty-eight proteins were exclusively identified in PG, while 52 were identified in NP. Moreover, 35 proteins were more abundant in PG and 29 proteins in NP (twofold change, p < .05). The NP group was mainly represented by proteins from "response to biotic stimuli and other organisms," "processes of cell death regulation," "peptidase regulation," "protein ubiquitination," and "ribosomal activity" GO categories. The most represented GO categories of the PG group were "assembly of multiprotein complexes," "catabolic processes," "lipid metabolism," and "binding to hemoglobin and haptoglobin." CONCLUSIONS: There are quantitative and qualitative differences in the proteome of GCF from periodontal sites according to the status of clinical progression of periodontitis. Progressive periodontitis sites are characterized by a protein profile associated with catabolic processes, immune response, and response to cellular stress, while stable periodontitis sites show a protein profile mainly related to wound repair and healing processes, cell death regulation, and chaperone-mediated autophagy. Understanding the etiopathogenic role of these profiles in progressive periodontitis may help to develop new diagnostic and therapeutic approaches.
Assuntos
Periodontite , Proteoma , Humanos , Líquido do Sulco Gengival/química , Proteômica , Periodontite/metabolismo , Progressão da DoençaRESUMO
During orthodontic treatment, diverse cytokines, enzymes, and osteolytic mediators produced within the teeth surrounding periodontal tissues determine the rate of alveolar bone remodeling and consequent teeth movement. In patients with teeth presenting reduced periodontal support, periodontal stability should be ensured during orthodontic treatment. Thus, therapies based on the application of low-intensity intermittent orthodontic forces are recommended. To determine if this kind of treatment is periodontally well tolerated, this study aimed to analyze the production of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, IL-17A, and matrix metalloproteinase (MMP)-8 in periodontal tissues of protruded anterior teeth with reduced periodontal support and undergoing orthodontic treatment. Patients with periodontitis-associated anterior teeth migration received non-surgical periodontal therapy and a specific orthodontic treatment involving controlled low-intensity intermittent orthodontic forces. Samples were collected before periodontitis treatment, after periodontitis treatment, and at 1 week to 24 months of the orthodontic treatment. During the 2 years of orthodontic treatment, no significant differences were detected in the probing depth, clinical attachment level, supragingival bacterial plaque, and bleeding on probing. In line with this, the gingival crevicular levels of RANKL, OPG, IL-6, IL-17A, and MMP-8 did not vary between the different evaluation time-points of the orthodontic treatment. When compared with the levels detected during the periodontitis, the RANKL/OPG ratio was significantly lower at all the analyzed time-points of the orthodontic treatment. In conclusion, the patient-specific orthodontic treatment based on intermittent orthodontic forces of low intensities was well tolerated by periodontally compromised teeth with pathological migration.
Assuntos
Reabsorção Óssea , Periodontite , Humanos , Reabsorção Óssea/metabolismo , Citocinas , Gengiva , Líquido do Sulco Gengival , Interleucina-17 , Interleucina-6 , Osteoprotegerina , Periodontite/metabolismo , Periodontite/terapia , Ligante RANK/análise , OrtodontiaRESUMO
Periodontitis is a chronic inflammatory disease characterized by the progressive and irreversible destruction of the periodontium. Its aetiopathogenesis lies in the constant challenge of the dysbiotic biofilm, which triggers a deregulated immune response responsible for the disease phenotype. Although the molecular mechanisms underlying periodontitis have been extensively studied, the regulatory mechanisms at the transcriptional level remain unclear. To generate transcriptomic data, we performed RNA shotgun sequencing of the oral mucosa of periodontitis-affected mice. Since genes are not expressed in isolation during pathological processes, we disclose here the complete repertoire of differentially expressed genes (DEG) and co-expressed modules to build Gene Regulatory Networks (GRNs) and identify the Master Transcriptional Regulators of periodontitis. The transcriptional changes revealed 366 protein-coding genes and 42 non-coding genes differentially expressed and enriched in the immune response. Furthermore, we found 13 co-expression modules with different representation degrees and gene expression levels. Our GRN comprises genes from 12 gene clusters, 166 nodes, of which 33 encode Transcription Factors, and 201 connections. Finally, using these strategies, 26 master regulators of periodontitis were identified. In conclusion, combining the transcriptomic analyses with the regulatory network construction represents a powerful and efficient strategy for identifying potential periodontitis-therapeutic targets.
Assuntos
Periodontite , Fatores de Transcrição , Animais , Camundongos , Fatores de Transcrição/genética , Periodontite/genética , Periodontite/patologia , Transcriptoma , Perfilação da Expressão Gênica , Periodonto/patologia , Redes Reguladoras de GenesRESUMO
AIM: To describe the radicular dentine thickness in mandibular first premolars presenting C-shaped root canals, to identify the canal walls with less thickness as potential danger zones. In addition, to describe the internal and external anatomical characteristics of these teeth and associate them with the dentine thickness. METHODOLOGY: A total of 70 mandibular first premolars presenting C-shaped root canals were examined. Their internal morphology was analysed using Vertucci's and Fan's criteria, and their external morphology was analysed using the ASUDAS score. Besides, the dentine thickness around the root canals was two/three-dimensionally determined at five root planes and quantified in the distal and the mesial aspects. RESULTS: According to Fan's, ASUDAS, and Vertucci's classifications, the most common canal configurations were category C3, grade 3, and type V, respectively. In Vertucci's type III anatomy, the mesial root wall of the lingual canal showed significantly less dentine thickness than the distal wall in the middle plane (p = .031). Similarly, in Vertucci's type V anatomy, significantly less dentine thickness was observed in the mesial root wall of the buccal and lingual canals in the middle plane (p < .001) and the buccal canal in the middle-apical plane (p = .014) than the distal root wall of these canals. In teeth with ASUDAS grade 3 and 4 scores, significantly less dentine thickness was observed in the mesial in comparison with the distal root wall of these canals. These differences were demonstrated in the middle and middle-apical planes (p < .001) of grade 3 teeth and the middle-apical plane (p < .001) of grade 4 teeth. In these root planes, the Ver1-AS3 and VerV-AS3 combinations presented a 4-times greater risk of presenting walls with a critical dentine thickness of 0.6 mm (odds ratio [OR] = 4, p = .025) than the combinations Ver1-AS2, VerV-AS2, VerV-AS4, and VerIII-AS3. CONCLUSIONS: The root canal system configuration of mandibular first premolars with C-shaped canals showed a wide range of anatomical variations. The lowest dentine thickness was located in the mesial wall of the canals in the middle and apical root thirds of Vertucci's type III and V anatomies and in teeth with deep radicular grooves scored as ASUDAS grades 3 and 4. In the middle and middle-apical planes, the presence of the combinations Ver1-AS3 and VerV-AS3 showed a high risk of presenting a critical dentine thickness of 0.6 mm. Therefore, these root canal walls with less dentine thickness represent potential instrumentation danger zones in mandibular first premolars with C-shaped canals.
Assuntos
Cavidade Pulpar , Mandíbula , Dente Pré-Molar/anatomia & histologia , Dente Pré-Molar/diagnóstico por imagem , Cavidade Pulpar/anatomia & histologia , Cavidade Pulpar/diagnóstico por imagem , Dentina/diagnóstico por imagem , Mandíbula/anatomia & histologia , Mandíbula/diagnóstico por imagem , Raiz Dentária/anatomia & histologia , Raiz Dentária/diagnóstico por imagem , Microtomografia por Raio-XRESUMO
Periodontitis is a non-communicable chronic inflammatory disease characterized by the progressive and irreversible breakdown of the soft periodontal tissues and resorption of teeth-supporting alveolar bone. The etiology of periodontitis involves dysbiotic shifts in the diversity of microbial communities inhabiting the subgingival crevice, which is dominated by anaerobic Gram-negative bacteria, including Porphyromonas gingivalis. Indeed, P. gingivalis is a keystone pathogen with a repertoire of attributes that allow it to colonize periodontal tissues and influence the metabolism, growth rate, and virulence of other periodontal bacteria. The pathogenic potential of P. gingivalis has been traditionally analyzed using classical biochemical and molecular approaches. However, the arrival of new techniques, such as whole-genome sequencing, metagenomics, metatranscriptomics, proteomics, and metabolomics, allowed the generation of high-throughput data, offering a suitable option for bacterial analysis, allowing a deeper understanding of the pathogenic properties of P. gingivalis and its interaction with the host. In the present review, we revise the use of the different -omics technologies and techniques used to analyze bacteria and discuss their potential in studying the pathogenic potential of P. gingivalis.
Assuntos
Infecções por Bacteroidaceae , Periodontite , Humanos , Porphyromonas gingivalis/genética , Infecções por Bacteroidaceae/microbiologia , Periodontite/patologia , Virulência , MetabolômicaRESUMO
The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for periodontitis as a low-grade inflammatory disease with systemic effects but also as an important source of potentially valuable clinical biomarkers of its systemic effects and susceptibility to other inflammatory conditions. Thus, we aimed to identify relevant genes tested as epigenetic systemic biomarkers in patients with periodontitis, based on the DNA methylation patterns and RNA expression profiles in peripheral immune cells. A detailed protocol was designed following the Preferred Reporting Items for Systematic Review and Meta-analysis -PRISMA guideline. Only cross-sectional and case-control studies that reported potential systemic biomarkers of periodontitis in peripheral immune cell types were included. DNA methylation was analyzed in leukocytes, and gene expression was in polymorphonuclear and mononuclear cells. Hypermethylation was found in TLR regulators genes: MAP3K7, MYD88, IL6R, RIPK2, FADD, IRAK1BP1, and PPARA in early stages of periodontitis, while advanced stages presented hypomethylation of these genes. TGFB1I1, VNN1, HLADRB4, and CXCL8 genes were differentially expressed in lymphocytes and monocytes of subjects with poorly controlled diabetes mellitus, dyslipidemia, and periodontitis in comparison with controls. The DAB2 gene was differentially overexpressed in periodontitis and dyslipidemia. Peripheral blood neutrophils in periodontitis showed differential expression in 163 genes. Periodontitis showed an increase in ceruloplasmin gene expression in polymorphonuclears in comparison with controls. Several genes highlight the role of the epigenetics of peripheral inflammatory cells in periodontitis that could be explored in blood as a source of biomarkers for routine testing.
Assuntos
Dislipidemias , Periodontite , Biomarcadores , Ceruloplasmina/genética , Estudos Transversais , Metilação de DNA , Dislipidemias/genética , Expressão Gênica , Humanos , Fator 88 de Diferenciação Mieloide/genética , Periodontite/genética , RNARESUMO
Senescent cells express a senescence-associated secretory phenotype (SASP) with a pro-inflammatory bias, which contributes to the chronicity of inflammation. During chronic inflammatory diseases, infiltrating CD4+ T lymphocytes can undergo cellular senescence and arrest the surface expression of CD28, have a response biased towards T-helper type-17 (Th17) of immunity, and show a remarkable ability to induce osteoclastogenesis. As a cellular counterpart, T regulatory lymphocytes (Tregs) can also undergo cellular senescence, and CD28- Tregs are able to express an SASP secretome, thus severely altering their immunosuppressive capacities. During periodontitis, the persistent microbial challenge and chronic inflammation favor the induction of cellular senescence. Therefore, senescence of Th17 and Treg lymphocytes could contribute to Th17/Treg imbalance and favor the tooth-supporting alveolar bone loss characteristic of the disease. In the present review, we describe the concept of cellular senescence; particularly, the one produced during chronic inflammation and persistent microbial antigen challenge. In addition, we detail the different markers used to identify senescent cells, proposing those specific to senescent T lymphocytes that can be used for periodontal research purposes. Finally, we discuss the existing literature that allows us to suggest the potential pathogenic role of senescent CD4+CD28- T lymphocytes in periodontitis.
Assuntos
Perda do Osso Alveolar , Periodontite , Antígenos CD28 , Humanos , Inflamação , Linfócitos T Reguladores , Células Th17RESUMO
Periodontitis is a chronic non-communicable disease caused by dysbiotic changes that affect the subgingival microbiota. During periodontitis, neutrophils play a central role in the initial recognition of bacteria, and their number increases with the appearance of the first signs of periodontal inflammation. Recent evidence has led to the proposition that neutrophils can also functionally polarize, determining selective activity patterns related to different diseases. Two well-defined neutrophil phenotypes have been described, the pro-inflammatory N1 subset and the suppressor N2 subset. To date, it has not been established whether these different neutrophil subtypes play a role in the pathogenesis of periodontitis. Thus, this scoping review aimed to determine whether there was evidence to suggest that the neutrophils present in periodontal tissues can be associated with certain phenotypes. The research question, population, concept, and context sought to identify original articles, in humans, that detected the presence of neutrophils in the periodontal tissues of people affected by periodontitis. Based on the search strategy, we found 3658 studies. After removing the papers with abstracts not related to the outcome measures and eligibility criteria, 16 articles were included for qualitative analysis. Several studies identified the presence of different neutrophil subsets, specifically, the naive, pro- and para-inflammatory, hyper-reactive and hyper-active, and high- and low-responder phenotypes. The existing evidence demonstrates the presence of pro-inflammatory, hyper-reactive and high-responder neutrophils in periodontal tissues affected with periodontitis. There is no evidence demonstrating the presence of the N1 or N2 phenotypes in periodontal tissues during periodontitis. However, the existence of pro-inflammatory phenotypes, which increase NETosis and degranulation, and increase the production of pro-inflammatory cytokines, could be suggestive of the N1 phenotypes.
Assuntos
Neutrófilos , Periodontite , Humanos , Neutrófilos/patologia , Periodontite/microbiologia , Periodonto/patologia , Inflamação/patologia , CitocinasRESUMO
BACKGROUND: Electrolyzed water has brought recent attention due to its antimicrobial properties. Indeed, electrolyzed water has been proposed to sterilize dental materials and instruments without compromising their structural integrity. In addition, electrolyzed water has been proposed as a mouthwash to control bacterial and viral oral infections without detrimental effects on the oral mucosa. However, no current consensus or evidence synthesis could indicate its potentially favorable use in the dental setting, particularly during the COVID-19 context. Therefore, this systematic review aimed to elucidate whether electrolyzed water could improve microbiologic control in the COVID-19 pandemic dental setting. METHODS: MEDLINE via Pubmed, EMBASE, Cochrane's CENTRAL, Scopus, LILACS, and Web of Science databases were searched up to September 2021 to identify experimental studies utilizing electrolyzed water for eliminating microorganisms in a dental setting. Besides, a manual and a grey literature search were performed. The data selection and extraction were performed individually and in duplicate. The Risk of Bias (RoB) was assessed with the Nature Publication Quality Improvement Project (NPQIP) score sheet. The study protocol was registered at PROSPERO CRD42020206986. RESULTS: From a total of 299 articles, 63 studies met the inclusion criteria. The included studies assessed several types of electrolyzed waters, which showed a high disinfection potential when used to deal with different oral conditions. Electrolyzed water demonstrated a broad antimicrobial spectrum and was highly efficient in the dental office disinfection against viruses, fungi, and bacteria, being compatible with most dental materials. In addition, electrolyzed water could protect against SARS-CoV-2 infection and contamination in the dental office. Regarding the RoB, only 35.18% of entries were answered as 'Yes', thus achieving less than half of the reporting sheet. CONCLUSION: Electrolyzed water effectively disinfects contaminated surfaces, dental materials, and equipment. Therefore, their use is recommendable in the SARS-CoV-2 pandemic dental setting.
Assuntos
COVID-19 , Pandemias , Humanos , Pandemias/prevenção & controle , SARS-CoV-2 , Água , COVID-19/prevenção & controle , Bactérias , Materiais DentáriosRESUMO
OBJECTIVE: This study aimed to determine the expression of distinct matrix metalloproteinases, cytokines, and bone resorptive factors in temporomandibular joint osteoarthritis (TMJ-OA) patients and their association with joint pain, mouth opening, and subchondral bone degeneration. MATERIALS AND METHODS: Twelve patients affected with TMJ-OA (n = 5), disk displacement without reduction (DDWoR) (n = 3), or disk displacement with reduction (DDWR) (n = 4) were selected. Joint pain was quantified by using visual analog scale, mouth opening was quantified at the maximum pain-free aperture, and bone degeneration was quantified using joint imaging. Synovial fluid samples were collected and immediately processed for cell and synovial fluid recovering. From cells, the MMP-1, MMP-2, MMP-8, MMP-13, IL-6, IL-23, and TNF-α expression was quantified by qPCR. From synovial fluid, the RANKL and OPG levels were quantified by ELISA. RESULTS: Higher levels of MMP-1, MMP-8, MMP-13, IL-6, IL-23, TNF-α, and RANKL/OPG ratio were detected in TMJ-OA compared with DDWoR and DDWR patients (p < .05). Joint pain significantly correlated with TNF-α levels (r = .975, p = .029). Besides, imaging signs of bone degeneration significantly correlated with RANKL/OPG ratio (r = .949, p = .042). Conversely, mouth opening did not correlate with any of the analyzed mediators. CONCLUSION: During TMJ-OA, a pathological response characterized by the overexpression of TNF-α and RANKL/OPG could be involved in joint pain and subchondral bone degeneration.
Assuntos
Osteoartrite , Articulação Temporomandibular , Artralgia , Citocinas , Humanos , Metaloproteinases da Matriz , Boca , Ligante RANK , Fator de Necrose Tumoral alfaRESUMO
Natural killer T (NKT) cells constitute a unique subset of T lymphocytes characterized by specifically interacting with antigenic glycolipids conjugated to the CD1d receptor on antigen-presenting cells. Functionally, NKT cells are capable of performing either effector or suppressor immune responses, depending on their production of proinflammatory or anti-inflammatory cytokines, respectively. Effector NKT cells are subdivided into three subsets, termed NKT1, NKT2, and NKT17, based on the cytokines they produce and their similarity to the cytokine profile produced by Th1, Th2, and Th17 lymphocytes, respectively. Recently, a new subgroup of NKT cells termed NKT10 has been described, which cooperates and interacts with other immune cells to promote immunoregulatory responses. Although the tissue-specific functions of NKT cells have not been fully elucidated, their activity has been associated with the pathogenesis of different inflammatory diseases with immunopathogenic similarities to periodontitis, including osteolytic pathologies such as rheumatoid arthritis and osteoporosis. In the present review, we revise and discuss the pathogenic characteristics of NKT cells in these diseases and their role in the pathogenesis of periodontitis; particularly, we analyze the potential regulatory role of the IL-10-producing NKT10 cells.
Assuntos
Células T Matadoras Naturais/fisiologia , Periodontite/etiologia , Animais , Antígenos CD1d/química , Citocinas/fisiologia , Glicolipídeos/química , Humanos , Ativação Linfocitária , Células T Matadoras Naturais/citologia , Periodontite/imunologiaRESUMO
OBJECTIVES: During periodontitis, chronic inflammation triggers soft tissue breakdown, and hyaluronan is degraded into fragments of low molecular weight (LMW-HA). This investigation aimed to elucidate whether LMW-HA fragments with immunogenic potential on T lymphocytes remain in periodontal tissues after periodontal treatment. MATERIALS AND METHODS: GCF samples were obtained from 15 periodontitis-affected patients and the LMW-HA, RANKL, and OPG levels were analyzed before and after 6 months of periodontal treatment by ELISA. Eight healthy individuals were analyzed as controls. Besides, human T lymphocytes were purified, exposed to infected dendritic cells, and pulsed with LMW-HA. Non-treated T lymphocytes were used as control. The expression levels of the transcription factors and cytokines that determine the Th1, Th17, and Th22 lymphocyte differentiation and function were analyzed by RT-qPCR. Similarly, the expression levels of RANKL and CD44 were analyzed. RESULTS: In the GCF samples of periodontitis-affected patients, higher levels of LMW-HA were detected when compared with those of healthy individuals (52.1 ± 15.4 vs. 21.4 ± 12.2, p < 0.001), and these increased levels did not decrease after periodontal therapy (52.1 ± 15.4 vs. 45.7 ± 15.9, p = 0.158). Similarly, the RANKL levels and RANKL/OPG ratios did not change after periodontal therapy. Furthermore, in human T lymphocytes, LMW-HA induced higher expression levels of the Th1, Th17, and Th22-related transcription factors and cytokines, as well as CD44 and RANKL, as compared with non-treated cells. CONCLUSIONS: In some patients, increased levels of LMW-HA persist in periodontal tissues after conventional periodontal therapy, and these remaining LMW-HA fragments with immunostimulatory potential could induce the polarization of a pathologic Th1/Th17/Th22-pattern of immune response on T lymphocytes. CLINICAL RELEVANCE: The persistence of increased levels of LMW-HA in periodontal tissues after periodontal therapy could favor the recurrence of the disease and further breakdown of periodontal supporting tissues.
Assuntos
Ácido Hialurônico , Periodontite , Citocinas , Humanos , Peso Molecular , Periodontite/tratamento farmacológico , Ligante RANK , Células Th17RESUMO
BACKGROUND: Implant-supported overdentures offer enhanced mechanical properties, which lead to better patient satisfaction and survival rates than conventional dentures. However, it is unclear whether these satisfaction levels and survival rates depend on the number of implants supporting the overdenture. Therefore, this systematic review aimed to compare maxillary overdentures supported by four or six splinted implants in terms of patient satisfaction, implant survival, overdenture survival, and prosthodontic complications. METHODS: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), and EMBASE databases were systematically searched and complemented by hand searching from 2000 to 2019, employing a combination of specific keywords. Studies comparing the use of four versus six implants for supporting overdentures with at least one-year of follow-up after prosthesis installation and including ten fully edentulous patients were included. The risk of bias (RoB) was analyzed with Cochrane's RoB 2 and Newcastle-Ottawa tools. Implants and prosthesis survival rates were analyzed by random-effects meta-analysis and expressed as risk ratios or risk differences, respectively, and by the non-parametric unpaired Fisher's test. RESULTS: A total of 15 from 1865 articles were included, and reported follow-up times after implant placement ranged from 1 to 10 years. Irrespective of the number of implants used, high scores were reported by all studies investigating patient satisfaction. Meta-analysis and non-parametric Fisher's test showed no statistical differences regarding the survival rate of implants (P = 0.34, P = 0.3) or overdentures (P = 0.74, P = 0.9) when using 4 versus 6 splinted implants to support overdentures, and no significant differences regarding prosthodontic complications were found between groups. Randomized studies presented high RoB and non-randomized studies presented acceptable quality. CONCLUSIONS: Within the limits of this systematic review, we can conclude that the bar-supported overdenture on four implants is not inferior to the overdenture supported by six implants for rehabilitating the edentulous maxilla, in terms of patient satisfaction, survival rates of implants and overdentures, and prosthodontic complications.
Assuntos
Implantes Dentários , Arcada Edêntula , Prótese Dentária Fixada por Implante , Retenção de Dentadura , Revestimento de Dentadura , Humanos , Maxila , Satisfação do PacienteRESUMO
AIM: T lymphocytes play a central role during the pathogenesis of periodontitis, and the imbalance between the pathogenic T-helper type 17 (Th17) and protective T-regulatory (Treg) lymphocytes determines the tooth-supporting alveolar bone resorption. Interleukin (IL)-35 is a novel anti-inflammatory cytokine with therapeutic properties in diseases whose pathogenesis is associated with the Th17/Treg imbalance; however, its role during periodontitis has not been established yet. This study aimed to elucidate whether IL-35 inhibits the alveolar bone resorption during periodontitis by modulating the Th17/Treg imbalance. MATERIALS AND METHODS: Mice with ligature-induced periodontitis were treated with locally or systemically administrated IL-35. As controls, periodontitis-affected mice without IL-35 treatment and non-ligated mice were used. Alveolar bone resorption was measured by micro-computed tomography and scanning electron microscopy. The Th17/Treg pattern of the immune response was analysed by qPCR, ELISA, and flow cytometry. RESULTS: IL-35 inhibited alveolar bone resorption in periodontitis mice. Besides, IL-35 induced less detection of Th17 lymphocytes and production of Th17-related cytokines, together with higher detection of Treg lymphocytes and production of Treg-related cytokines in periodontitis-affected tissues. CONCLUSION: IL-35 is beneficial in the regulation of periodontitis; particularly, IL-35 inhibited alveolar bone resorption and this inhibition was closely associated with modulation of the periodontal Th17/Treg imbalance.
Assuntos
Perda do Osso Alveolar , Periodontite , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/prevenção & controle , Animais , Interleucinas , Camundongos , Linfócitos T Reguladores , Células Th17 , Microtomografia por Raio-XRESUMO
OBJECTIVES: To explore the macrophage profiles in symptomatic and asymptomatic forms of AP through phenotypic and functional analyses. MATERIAL AND METHODS: Cross-sectional study. Apical tissue/lesion samples were collected from patients with clinical diagnosis of AAP (n = 51) or SAP (n = 45) and healthy periodontal ligament (HPL) from healthy patients as controls (n = 14), all with indication of tooth extraction. Samples were digested, cells were stained for CD14, M1 (CD64, CD80), and M2 (CD163, CD206) phenotypic surface markers and analyzed by flow cytometry. Functional cytokine profiles L-6, IL-12, TNF-α, IL-23 (M1), IL-10, and TGF-ß (M2) were determined by qPCR. RESULTS: Higher macrophage M1/M2 ratio (CD64+CD80+/CD163+CD206+) along with lower CD163 mean fluorescence intensity (MFI) were found in SAP compared to AAP and controls (p < 0.05). IL-6, IL-12, TNF-α, IL-23 (M1), and IL-10 mRNA (M2) were upregulated, whereas TGF-ß mRNA (M2) was downregulated in apical lesions compared to controls. Specifically, IL-6 and IL-23 (M1) were upregulated in SAP compared with AAP and controls (p < 0.05). The data were analyzed with Kruskal-Wallis test. CONCLUSIONS: Macrophages exhibited a polarization switch towards M1 in AL. SAP exhibited a reduced M2 differentiation profile based on a reduction of CD163 expression levels in SAP over AAP. Specifically, IL-6 and IL-23 were augmented SAP over AAP, suggesting a role in the severity of apical lesions. CLINICAL RELEVANCE: Deciphering the macrophage polarization and functions in apical periodontitis can contribute to explain AP dynamics, its clinical presentation and systemic impact.
Assuntos
Periodontite Periapical , Ápice Dentário , Estudos Transversais , Humanos , Macrófagos , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: This study assessed IL-1ß and RANK-L levels in vivo and color stability of non-vital teeth bleached using hydrogen (35%) and carbamide (37%) peroxides 3 months after treatment. MATERIALS AND METHODS: Fifty teeth were randomly divided into two groups(n = 25):35% hydrogen peroxide (HP) or 37% carbamide peroxide (CP). Four sessions of intracoronal walking-bleach procedure were performed. IL-1ß and RANK-L levels were assessed from gingival crevicular fluid samples (from three vestibular and three palatines sites) at eight different time-points: at the beginning of the study (baseline), after four sessions of intracanal bleaching, and at 1 week, 1 month, and 3 months posttreatment. The color variations were visually detected using Vita bleach shade guide (ΔSGU). RESULTS: Significant increases of IL-1ß and RANK-L levels were detected at all time-points (all P < .05) when comparing each time-point to baseline, and a high correlation (>0.8-Spearman) between variables. According the ΔSGU values, a color change of five for HP and four for CP were detected. CONCLUSIONS: Non-vital walking bleach technique promotes an increase in IL-1ß and RANKL levels in periodontal tissues and also, it is maintained until the third-month posttreatment. CLINICAL SIGNIFICANCE: The internal whitening of teeth increases the levels of cytokines associated with inflammation and bone resorption 3 months after the whitening procedure is finished; this should warn of possible harmful effects of this whitening technique.
Assuntos
Clareadores Dentários , Clareamento Dental , Descoloração de Dente , Cor , Seguimentos , Humanos , Peróxido de Hidrogênio , Peróxidos , UreiaRESUMO
This systematic review aimed to: (a) generate a descriptive synthesis of preclinical studies assessing the therapeutic potential of regulatory T lymphocytes (Tregs) to arrest periodontitis, (b) evaluate the methodological heterogeneity of the reviewed animal studies and (c) assess the risk of bias (RoB) of the included studies. The electronic search for animal studies included the MEDLINE, EMBASE, Web of Science and LILACS databases. In addition, a manual search assessed the high-ranked scientific journals in "periodontics/immunology" and the references listed in the included studies. There were no language, year or publication status restrictions. Two independent reviewers selected and extracted the data, and Cohen's Kappa coefficient was calculated to determine the inter-examiner agreement. The Systematic Review Center for Laboratory Animal Experimentation's (SYRCLE) tool was used to assess the RoB. A total of 21 of the 425 studies obtained from the database search were included. Treg function was mainly described in Porphyromonas gingivalis-induced periodontitis (57.1%) in mice (76.2%), where Treg suppression was strongly related to disease progression and Treg induction was strongly related to immuno-inflammatory response reduction. Of those 21 studies, eight included eight animal experiments using three distinct therapeutic approaches, including: P. gingivalis-driven immunization (n = 3), retinoic acid inoculation (n = 2) and anti-inflammatory molecules in polymeric carriers (n = 3), which could modulate the Treg activity through cytokine production (interleukin-10 and transforming growth factor-ß1), CC-chemokine- and CC-chemokine receptor-mediated chemoattraction (CCL22 and CCR4) or Th17-associated receptor activator of nuclear factor κB ligand (RANKL) downregulation. However, the studies with animal experiments did not specify the randomization sequences and housing conditions that were used, and therefore, 42.11% of the entries were rated as unclear RoB. Distinct therapeutic strategies involving Tregs could potentially suppress the immuno-inflammatory response and restore alveolar bone homeostasis during periodontitis. Nevertheless, important methodological variability, poor reporting of treatment effect estimates and unclear RoB suggest using caution when assessing the results of these studies.
Assuntos
Periodontite/imunologia , Periodontite/terapia , Linfócitos T Reguladores/imunologia , Animais , Infecções por Bacteroidaceae , Quimiocinas CC/metabolismo , Citocinas/metabolismo , Bases de Dados Bibliográficas , Humanos , Camundongos , Periodontite/microbiologia , Porphyromonas gingivalis , Ligante RANK/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Over the past few years, the importance of interleukin-22 (IL-22) and T-helper (Th)22 lymphocytes in the pathogenesis of periodontitis has become apparent; however, there are still aspects that are not addressed yet. Cells expressing IL-22 and aryl hydrocarbon receptor (AhR), transcription factor master switch gene implicated in the differentiation and function of Th22 lymphocytes, have been detected in periodontal tissues of periodontitis-affected patients. In addition, IL-22 has been associated with osteoclast differentiation and their bone resorptive activity in vitro. However, the destructive potential of IL-22-expressing AhR+ Th22 lymphocytes over periodontal tissues during periodontitis has not been demonstrated in vivo yet. Therefore, this study aimed to analyze whether IL-22-expressing CD4+ AhR+ T lymphocytes detected in periodontal lesions are associated with alveolar bone resorption during experimental periodontitis. MATERIAL AND METHODS: Using a murine model of periodontitis, the expression levels of IL-22 and AhR, as well as the Th1-, Th2-, Th17- and T regulatory-associated cytokines, were analyzed in periodontal lesions using qPCR. The detection of CD4+ IL-22+ AhR+ T lymphocytes was analyzed in periodontal lesions and cervical lymph nodes that drain these periodontal lesions using flow cytometry. In addition, the expression of the osteoclastogenic mediator called receptor activator of nuclear factor-κB ligand (RANKL) was analyzed by qPCR, western blot, and immunohistochemistry. Finally, alveolar bone resorption was analyzed using micro-computed tomography and scanning electron microscopy, and the bone resorption levels were correlated with IL-22 and RANKL expression. RESULTS: Higher levels of IL-22, AhR, and RANKL, as well as IL-1ß, IL-6, IL-12, IL-17, IL-23, and TNF-α, were expressed in periodontal lesions of infected mice compared with periodontal tissues of sham-infected and non-infected controls. Similarly, high RANKL immunoreaction was observed in periodontal tissues of infected mice; however, few or absent RANKL immunoreaction was observed in controls. This association between RANKL and periodontal infection was ratified by western blot. Furthermore, a higher detection of CD4+ IL-22+ AhR+ T lymphocytes was found in periodontal lesions and cervical lymph nodes that drain these periodontal lesions in infected mice compared with non-infected controls. Finally, the increased IL-22 and RANKL expression showed positive correlation between them and with the augmented alveolar bone resorption observed in experimental periodontal lesions. CONCLUSION: This study demonstrates the increase of IL-22-expressing CD4+ AhR+ T lymphocytes in periodontitis-affected tissues and shows a positive correlation between IL-22, RANKL expression, and alveolar bone resorption.
Assuntos
Perda do Osso Alveolar , Reabsorção Óssea , Interleucinas , Periodontite , Ligante RANK , Animais , Humanos , Interleucinas/metabolismo , Camundongos , Periodontite/metabolismo , Ligante RANK/farmacologia , Receptores de Hidrocarboneto Arílico , Microtomografia por Raio-X , Interleucina 22RESUMO
Periodontitis is an inflammatory disease, in which the host immuno-inflammatory response against the dysbiotic subgingival biofilm leads to the breakdown of periodontal tissues. Most of the available treatments seem to be effective in the short-term; nevertheless, permanent periodical controls and patient compliance compromise long-term success. Different strategies have been proposed for the modulation of the host immune response as potential therapeutic tools to take a better care of most susceptible periodontitis patients, such as drug local delivery approaches. Though, maintaining an effective drug concentration for a prolonged period of time has not been achieved yet. In this context, advanced drug delivery strategies using biodegradable nanocarriers have been proposed to avoid toxicity and frequency-related problems of treatment. The versatility of distinct nanocarriers allows the improvement of their loading and release capabilities and could be potentially used for microbiological control, periodontal regeneration, and/or immunomodulation. In the present review, we revise and discuss the most frequent biodegradable nanocarrier strategies proposed for the treatment of periodontitis, including polylactic-co-glycolic acid (PLGA), chitosan, and silica-derived nanoparticles, and further suggest novel therapeutic strategies.