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1.
Biomedicines ; 9(2)2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33671221

RESUMO

DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2'-deoxycytidine) (1 mg/kg/day) or vehicle treatment. We evaluated bone resorption, osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) and mRNA expression of anti-inflammatory molecules using cluster differentiation 14 positive (CD14+) monocytes from human peripheral blood. Our data showed that decitabine inhibited bone loss and osteoclast differentiation experimental periodontitis, and suppressed osteoclast CD14+ human monocytes; and conversely, that it increased bone mineralization in osteoblastic cell line MC3T3-E1 in a concentration-dependent manner. In addition to increasing IL10 (interleukin-10), TGFB (transforming growth factor beta-1) in CD14+ monocytes, decitabine upregulated KLF2 (Krüppel-like factor-2) expression. Overexpression of KLF2 protein enhanced the transcription of IL10 and TGFB. On the contrary, site-directed mutagenesis of KLF2 binding site in IL10 and TFGB abrogated luciferase activity in HEK293T cells. Decitabine reduces bone loss in a mouse model of periodontitis by inhibiting osteoclastogenesis through the upregulation of anti-inflammatory cytokines via KLF2 dependent mechanisms. DNA methyltransferase inhibitors merit further investigation as a possible novel therapy for periodontitis.

2.
Arch Oral Biol ; 107: 104508, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31382162

RESUMO

OBJECTIVE: The aim of this study was to investigate the functionality of ATC/TTC (Hap-1) and ATT/TTC (Hap-2) Interleukin (IL) 8 gene haplotypes in the response of neutrophils to Gram-negative bacteria associated with periodontitis. DESIGN: Neutrophils were isolated by gradient centrifugation from whole peripheral blood of systemically healthy individuals presenting the two IL8 gene haplotypes. Neutrophils were stimulated with P. gingivalis, A. actinomycetemcomitans and PMA/ionomycin. Cytokine gene expression (RT-qPCR) and migration/chemotaxis (boyden chamber assay) were compared according to the presence of Hap-1 or Hap-2 haplotypes. Protein production was also evaluted in the multiplex assay using the mixed population of leukocytes present in the whole blood from the same individuals. The influence of these two haplotypes on the IL8 promoter activity was assessed in gene-reporter experiments. RESULTS: Hap-1 haplotype in neutrophils and leukocytes exacerbated the response to stimulation with Gram-negative bacteria, with higher levels of TNF-α (mRNA and protein), IL-1ß, IL-2R and IFN-γ (protein) and with increased chemotaxis. Presence of the T allele at the rs4071 polymorphism (alias -251) was associated with increased activity of IL8 proximal promoter. CONCLUSIONS: Neutrophils and leukocytes carrying the Hap-1 haplotype (ATC/TTC) in the IL8 gene present an enhanced response to stimulation with Gram-negative bacteria associated with periodontitis. Presence of the T allele (rs4073) in the IL8 proximal promoter increases transcription activity.


Assuntos
Bactérias Gram-Negativas , Interleucina-8/genética , Neutrófilos/imunologia , Periodontite/genética , Citocinas/imunologia , Predisposição Genética para Doença , Haplótipos , Humanos , Periodontite/microbiologia , Projetos Piloto , Regiões Promotoras Genéticas
3.
J Clin Periodontol ; 46(8): 819-829, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31131910

RESUMO

AIM: The purpose of this study was to determine inflammatory and epigenetic features following induction of oral and gut dysbiosis in experimental periodontitis in order to examine the interplay between oral and systemic infection. MATERIALS AND METHODS: Periodontitis was induced in 6- to 8-week-old C57BL/6 mice by (a) Ligature placement (Lig group) (oral challenge); (b) P. gingivalis gavage (Pg group) (systemic challenge); and (c) the combination of the two models oral and systemic challenge (Pg + Lig). The duration of the experiment was 60 days, and the animals were then sacrificed for analyses. Alveolar bone loss was assessed, and a multiplex immunoassay was performed. Maxillae and gut tissues were immunostained for DNMT3b (de novo methylation marker), B and T lymphocyte attenuator (BTLA) and IL-18R1 (inflammation markers). RESULTS: Pg and Pg + Lig groups exhibited higher bone loss when compared to Sham. BAFF, VEGF, RANKL, RANTES and IP-10 were significantly higher with Pg gavage. Likewise, DNMT3b was overexpressed in both gut and maxilla after the Pg administration. The same pattern was observed for BTLA and IL-18R1 in gut tissues. CONCLUSIONS: The systemic microbial challenge either alone or in combination with local challenge leads to distinct patterns of inflammatory and epigenetic features when compared to simply locally induced experimental periodontitis.


Assuntos
Perda do Osso Alveolar , Periodontite , Animais , Modelos Animais de Doenças , Epigênese Genética , Camundongos , Camundongos Endogâmicos C57BL , Porphyromonas gingivalis
4.
Microb Pathog ; 131: 53-64, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30940608

RESUMO

Polymorphonuclear neutrophils (PMNs) are indispensable in fighting infectious microbes by adopting various antimicrobial strategies including phagocytosis and neutrophil extracellular traps (NETs). Although the role and importance of PMNs in periodontal disease are well established, the specific molecular mechanisms involved in NET formation are yet to be characterized. In the present study, we sought to determine the role of periodontal pathogen on NET formation by utilizing Fusobacterium nucleatum. Our data demonstrates that F. nucleatum activates neutrophils and induces robust NETosis in a time-dependent manner via the upregulation of the Nucleotide oligomerization domain 1 (NOD1) and NOD2 receptors. Furthermore, CRISPR/Cas9 knockout of HL-60 cells and the use of ligands/inhibitors confirmed the involvement of NOD1 and NOD2 receptors in F. nucleatum-mediated NET formation. When treated with NOD1 and NOD2 inhibitors, we observed a significant downregulation of peptidylarginine deiminase 4 (PAD4) activity. In addition, neutrophils showed a significant increase and decrease of myeloperoxidase (MPO) and neutrophil elastase (NE) when treated with NOD1/NOD2 ligands and inhibitors, respectively. Taken together, CRISPR/Cas9 knockout of NOD1/NOD2 HL-60 cells and inhibitors of NOD signaling confirmed the role of NLRs in F. nucleatum-mediated NETosis. Our data demonstrates an important pathway linking NOD1 and NOD2 to NETosis by F. nucleatum, a prominent microbe in periodontal biofilms. This is the first study to elucidate the role of NOD-like receptors in NETosis and their downstream signaling network.


Assuntos
Fusobacterium nucleatum/patogenicidade , Neutrófilos/imunologia , Neutrófilos/metabolismo , Proteína Adaptadora de Sinalização NOD1/metabolismo , Proteína Adaptadora de Sinalização NOD2/metabolismo , Periodontite/metabolismo , Biofilmes , Sistemas CRISPR-Cas/genética , Regulação para Baixo , Células HL-60 , Histonas/metabolismo , Humanos , Elastase de Leucócito/metabolismo , Periodontite/microbiologia , Peroxidase/metabolismo , Fagocitose , Proteína-Arginina Desiminase do Tipo 4 , Desiminases de Arginina em Proteínas/metabolismo , Transdução de Sinais
5.
Gene ; 689: 152-160, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30562605

RESUMO

Individuals carrying the ATC/TTC haplotype (Hap-1) in the interleukin 8 (IL8) gene were reported as more susceptible to chronic periodontitis (CP), an infectious disease associated with Gram-negative bacteria, in comparison to patients with the ATT/TTC haplotype (Hap-2). This study investigated the functionality of the IL8 haplotypes in lymphocytes and monocytes of individuals carrying the Hap-1 or Hap-2 IL8 haplotypes in the response to CP-associated Gram-negative bacteria (periodontopathogens). Peripheral blood was collected from 6 subjects carrying each haplotype, and their immune cells were challenged with periodontopathogens or phorbol 12-myristate 13-acetate (PMA) plus Ionomycin. Depending on the immune cell type (lymphocytes or monocyte-derived macrophages) the assessed outcomes were: phenotypical polarization, gene expression, phagocytic activity, chemotaxis and production of reactive oxygen species (ROS). Subjects carrying the Hap-1 haplotype showed increased expression of IL8 and TNFA and significantly skewing towards pro-inflammatory Th1/M1/Th17 phenotypes. There was increased percentage of ROS-producing monocyte-derived macrophages from individuals carrying the Hap-1 haplotype. Cells from individuals presenting the Hap-2 haplotype had an overall attenuated response to periodontopathogens, with a significant shift towards the Treg phenotype. In conclusion, the IL8 haplotypes showed to be functional both in monocyte-derived macrophages and lymphocytes. The Hap-1 haplotype previously associated with increased susceptibility to CP demonstrated greater skewing to pro-inflammatory Th1/M1/Th17 phenotypes and production of ROS.


Assuntos
Periodontite Crônica , Bactérias Gram-Negativas/imunologia , Bactérias Gram-Negativas/patogenicidade , Interleucina-8/genética , Linfócitos/metabolismo , Macrófagos/metabolismo , Aggregatibacter actinomycetemcomitans/imunologia , Aggregatibacter actinomycetemcomitans/patogenicidade , Periodontite Crônica/genética , Periodontite Crônica/imunologia , Periodontite Crônica/microbiologia , Feminino , Predisposição Genética para Doença , Infecções por Bactérias Gram-Negativas/genética , Infecções por Bactérias Gram-Negativas/imunologia , Haplótipos , Humanos , Interleucina-8/metabolismo , Linfócitos/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Fenótipo , Porphyromonas gingivalis/imunologia , Porphyromonas gingivalis/patogenicidade
6.
Pathog Dis ; 75(7)2017 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-28859277

RESUMO

This study aimed to evaluate the association between haplotypes in the interleukin 8 (IL8) and IL4 genes previously associated to chronic periodontitis (CP) and the levels of Aggregatibacter actinomycetemcomitans (A.a.) in subgingival sites of patients with and without CP. Moreover, multifaceted evaluations were made to search associations among patients' genetic background with the A.a. levels and previous clinical/immunological/microbiological findings. Subgingival sites (n = 596) of 104 patients were divided into susceptible to CP by the IL8 haplotype ATC/TTC (IL8+); non-susceptible to CP by the IL8 AGT/TTC (IL8-); susceptible to CP by the IL4 TCI/CCI (IL4+); protection against CP by the IL4 TTD/CTI (IL4-). Subgingival biofilm samples from diseased and healthy sites of CP patients and from control sites of health patients were obtained for absolute quantification of A.a. by quantitative real-time polymerase chain reaction. For diseased sites, samples were collected before and 45 days after periodontal treatment. The IL4 but not the IL8 haplotypes were associated with levels of A.a. (in both periods). After periodontal treatment, higher levels of A.a. were found in subgingival sites of (IL4-) patients, and higher levels of IL-4 were associated with deeper probing pockets in these same patients. Significant correlations were found among genetic (patients carrying IL8 or IL4 haplotypes), microbiological and immunological data showing the interrelationship of different factors in the CP.


Assuntos
Aggregatibacter actinomycetemcomitans/genética , Biofilmes/crescimento & desenvolvimento , Periodontite Crônica/genética , Predisposição Genética para Doença , Interleucina-4/genética , Interleucina-8/genética , Polimorfismo Genético , Adulto , Aggregatibacter actinomycetemcomitans/crescimento & desenvolvimento , Aggregatibacter actinomycetemcomitans/isolamento & purificação , Aggregatibacter actinomycetemcomitans/patogenicidade , Carga Bacteriana , Periodontite Crônica/imunologia , Periodontite Crônica/microbiologia , Periodontite Crônica/terapia , Feminino , Expressão Gênica , Haplótipos , Humanos , Interleucina-4/imunologia , Interleucina-8/imunologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , RNA Ribossômico 16S/genética , Curetagem Subgengival
7.
J Clin Periodontol ; 44(12): 1192-1207, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28782128

RESUMO

AIM: Several papers have considered the potential relationship between periodontitis and lipid parameters. The present systematic review, meta-analysis and meta-regression studies focused on investigating whether serum lipid parameter levels were elevated in patients with periodontal disease (PD; without altered systemic conditions) in comparison with periodontally healthy subjects. MATERIALS AND METHODS: Eligible studies were those with data about serum lipid parameter levels in non-smoking subjects with and without chronic periodontitis, who are generally healthy and not taking any medication for dyslipidaemia. Mean differences and 95% confidence intervals for total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were obtained from all the selected studies. RESULTS: A total of 19 publications were included for meta-analysis. Participants with chronic periodontitis presented significantly higher serum levels of LDL and triglycerides (p = .003 and p < .0001, respectively). The total cholesterol was higher in the PD group, but without significant difference in comparison with healthy participants. Significantly (p = .0005) lower HDL serum levels were found in patients with chronic periodontitis than in healthy subjects. CONCLUSIONS: Even considering the limitations of this meta-analysis, it is suggested that PD is significantly associated with reduction in HDL and elevation of LDL and triglyceride concentrations. This analysis supports the rationale that periodontal disease is associated with lipid metabolic control.


Assuntos
Lipídeos/sangue , Doenças Periodontais/sangue , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Periodontite Crônica/sangue , Bases de Dados Factuais , Feminino , Humanos , Metabolismo dos Lipídeos , Masculino , Metanálise como Assunto , Triglicerídeos/sangue
8.
Int J Mol Sci ; 18(6)2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28617311

RESUMO

This study aimed to investigate whether the -1026(A>C)(rs2779249) and +2087(A>G)(2297518) polymorphisms in the NOS2 gene were associated with chronic periodontitis (CP) and with salivary levels of nitrite (NO2-) and/or nitrate + nitrite (NOx). A group of 113 mixed-race patients were subjected to periodontal, genetic, and biochemical evaluations (65 CP/48 periodontally healthy subjects). DNA was extracted from oral epithelial cells and used for genotyping by polymerase chain reaction (real-time). Salivary NOx concentrations were determined using an ozone-based chemiluminescence assay. Association of CP with alleles and genotypes of the -1026(A>C) polymorphism was found (X² test, p = 0.0075; 0.0308), but this was not maintained after multiple logistic regression, performed to estimate the effect of covariates and polymorphisms in CP. This analysis demonstrated, after correction for multiple comparisons, that only the female gender was significantly associated with CP. Polymorphisms analyzed as haplotypes were not associated with CP. NOx levels were significantly higher in the control group of heterozygous individuals for both polymorphisms. In conclusion, the female gender was significantly associated with CP, and higher levels of salivary NOx were found in control subjects and associated with the heterozygous state of the NOS2 polymorphisms, reinforcing the potential of NO metabolites as markers of periodontitis status.


Assuntos
Periodontite Crônica/genética , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico/análise , Polimorfismo de Nucleotídeo Único , Adulto , Periodontite Crônica/patologia , Feminino , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Saliva/química
9.
Medicine (Baltimore) ; 96(22): e6932, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28562542

RESUMO

BACKGROUND: Current publications present contradictory findings regarding interleukin-8 (IL-8) levels in patients with chronic periodontitis (CP). This systematic review compile evidences of the IL8 mRNA and protein levels in gingival tissue, saliva, and gingival crevicular fluid (GCF) investigated in patients with CP. Moreover, 2 meta-analyses were made focusing on the IL-8 levels in GCF and saliva of patients with or without CP. METHODS: Electronic searches of the PubMed, Web of Science, and Scopus databases were conducted for publications up to February 2016 that investigated the levels of IL-8 detected in individuals with CP compared with health individuals. A total of 31 publications were included in the systematic review. For meta-analyses, the strength of association was calculated by pooled odds ratios with 95% confidence intervals using RevMan 5.1 software. Heterogeneity was examined using Higgins I-squared, tau-squared, and χ tests. RESULTS: In biopsies of gingival tissue of CP patients, all studies found higher IL8 mRNA levels, and the majority of studies showed higher IL-8 protein levels in this tissue of individuals with moderate to severe CP. Four studies investigating the IL-8 levels in saliva showed inconclusive results. In spite of some studies seemed to indicate higher levels of IL-8 in GCF of CP patients, the meta-analysis results showed significantly lower IL-8 levels (pg/µL) in GCF of CP patients in comparison with periodontally healthy subjects. CONCLUSIONS: We concluded that IL8 gene expression and IL-8 protein levels were higher in gingival tissues of CP patients when compared to periodontally health individuals. Meta-analysis of studies that measured IL-8 (pg/uL) in GCF found lower levels in CP patients. There are conflicting evidences regarding IL-8 levels in saliva.


Assuntos
Periodontite Crônica/metabolismo , Interleucina-8/metabolismo , Biomarcadores/metabolismo , Humanos
10.
Sci Rep ; 6: 31180, 2016 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-27499075

RESUMO

Interleukin-8 (IL-8) gene polymorphisms have been considered as susceptibility factors in periodontal disease. However, the functional roles of IL-8 gene haplotypes have not been investigated. Here, we demonstrate for the first time the use of the CRISPR/Cas9 system to engineer the IL-8 gene, and tested the functionality of different haplotypes. Two sgRNAs vectors targeting the IL-8 gene and the naked homologous repair DNA carrying different haplotypes were used to successfully generate HEK293T cells carrying the AT genotype at the first SNP - rs4073 (alias -251), TT genotype at the second SNP - rs2227307 (alias +396), TC or CC genotypes at the third SNP - rs2227306 (alias +781) at the IL-8 locus. When stimulated with Poly I:C, ATC/TTC haplotype, cells significantly up-regulated the IL-8 at both transcriptional and translational levels. To test whether ATC/TTC haplotype is functional, we used a trans-well assay to measure the transmigration of primary neutrophils incubated with supernatants from the Poly I:C stimulation experiment. ATC/TTC haplotype cells significantly increased transmigration of neutrophils confirming the functional role for this IL-8 haplotype. Taken together, our data provides evidence that carriage of the ATC/TTC haplotype in itself may increase the influx of neutrophils in inflammatory lesions and influence disease susceptibility.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Genoma Humano , Neutrófilos/metabolismo , Polimorfismo de Nucleotídeo Único , Biossíntese de Proteínas/genética , Transcrição Gênica/genética , Células HEK293 , Humanos , Interleucina-8/biossíntese , Interleucina-8/genética , Poli I-C/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos
11.
Caries Res ; 50(3): 310-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27179118

RESUMO

Despite some evidence of genetic and environmental factors on molar-incisor hypomineralization (MIH), its aetiology remains unclear. This family-based genetic association study aimed more comprehensively to investigate the genetic carriage potentially involved in MIH development. DNA was obtained from buccal cells of 391 individuals who were birth family members of 101 Brazilian nuclear families. Sixty-three single nucleotide polymorphisms (SNPs) were investigated in 21 candidate genes related to amelogenesis using the TaqMan™ OpenArray™ Genotyping platform. All SNPs were genotyped in 165 birth family members unaffected by MIH, 96 with unknown MIH status and 130 affected individuals (50.7% with severe MIH). Association analysis was performed by the transmission/disequilibrium test (TDT), and statistical results were corrected using the false discovery rate. Significant results were obtained for SNPs rs7821494 (FAM83H gene, OR = 3.7; 95% CI = 1.75-7.78), rs34367704 (AMBN gene, OR = 2.7; 95% CI = 1.16-6.58), rs3789334 (BMP2 gene, OR = 2.9; 95% CI = 1.34-6.35), rs6099486 (BMP7 gene, OR = 2.2; 95% CI = 1.14-4.38), rs762642 (BMP4 gene, OR = 2.3; 95% CI = 1.38-3.65), rs7664896 (ENAM gene, OR = 2.1; 95% CI = 1.19-3.51), rs1711399 (MMP20 gene, OR = 0.4; 95% CI = 0.20-0.72), rs1711423 (MMP20 gene, OR = 2.1; 95% CI = 1.18-3.61), rs2278163 (DLX3 gene, OR = 2.8; 95% CI = 1.26-6.41), rs6996321 (FGFR1 gene, OR = 2.7; 95% CI = 1.20-5.88), and rs5979395 (AMELX gene, OR = 11.7; 95% CI = 1.63-84.74). Through this family-based association study, we concluded that variations in genes related to amelogenesis were associated with the susceptibility to develop MIH. This result is in agreement with the multifactorial idea of the MIH aetiology, but further studies are necessary to investigate more thoroughly the factors that could influence MIH.


Assuntos
Amelogênese/genética , Hipoplasia do Esmalte Dentário/genética , Incisivo/patologia , Dente Molar/patologia , Criança , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Núcleo Familiar , Polimorfismo de Nucleotídeo Único
12.
J Biomed Mater Res A ; 103(10): 3397-406, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25850694

RESUMO

This study aimed to evaluate the potential of bacterial cellulose-hydroxyapatite (BC-HA) composites associated with osteogenic growth peptide (OGP) or pentapeptide OGP(10-14) in bone regeneration in critical-size calvarial defects in mice. In this study, the BC-HA, BC-HA-OGP, and BC-HA-OGP(10-14) membranes were analyzed at 3, 7, 15, 30, 60, and 90 days. In each period, the specimens were evaluated by micro-computed tomography (µCT), descriptive histology, gene expression of bone biomarkers by qPCR and VEGFR-2 (vascular endothelial growth factor) quantification by ELISA. Three days post-operative, Runx2, Tnfrsf11b and Bglap bone biomarkers were upregulated mainly by BC-HA OGP and BC-HA OGP(10-14) membranes, suggesting an acceleration of the osteoblast differentiation/activity with the use of these biomaterials. At 60 and 90 days, a high percentage of bone formation was observed by µCT for BC-HA and BC-HA OGP(10-14) membranes. High expression of some bone biomarkers, such as Alpl, Spp1, and Tnfrsf11b, was also observed for the same membranes on days 60 and 90. In conclusion, the BC-HA membrane promoted a better bone formation in critical-size mice calvarial defects. Nevertheless, incorporation of the peptides at the concentration of 10(-9) mol L(-1) did not improve bone regeneration potential in the long-term.


Assuntos
Bactérias/química , Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos , Celulose , Durapatita , Histonas , Peptídeos e Proteínas de Sinalização Intercelular , Crânio/lesões , Animais , Antígenos de Diferenciação/metabolismo , Substitutos Ósseos/química , Substitutos Ósseos/farmacologia , Celulose/química , Celulose/farmacologia , Modelos Animais de Doenças , Durapatita/química , Durapatita/farmacologia , Histonas/química , Histonas/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Masculino , Teste de Materiais , Camundongos , Camundongos Endogâmicos BALB C , Crânio/metabolismo , Crânio/patologia
13.
Hum Immunol ; 74(12): 1688-95, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24007654

RESUMO

Different IL4 haplotypes were associated to susceptibility to/or protection against chronic periodontitis (CP). The aim of this study was to investigate if individuals carrying different haplotypes would present differences in clinical periodontal parameters and in the IL-4 levels at baseline, 45 and 90 days after non-surgical periodontal therapy. 62 patients were subdivided: genetically protected without CP (PH), genetically protected with CP (PCP), genetically susceptible with CP (SCP), genetically susceptible without CP (healthy) (SH). Clinical examination and gingival crevicular fluid (GCF) collection were performed for all patients, and IL-4 levels were measured by ELISA. At baseline, higher values for plaque index (PI, p = 0.013), gingival index (GI, p = 0.005) were observed for the SCP group in comparison to the PCP group but not after the completion of periodontal therapy. 45 and 90 days after the non-surgical therapy, PCP demonstrated significantly higher IL-4 levels than the SCP (p = 0.000002). Correlation analysis showed different results between clinical parameters and IL-4 production or GCF volume for groups with different genetic loads. The IL4 gene which was previously associated with susceptibility to CP was related with differences in the IL-4 protein levels in the GCF. However, independent of genetic carriage, individuals responded similarly to this therapy.


Assuntos
Periodontite Crônica/genética , Periodontite Crônica/metabolismo , Predisposição Genética para Doença , Haplótipos , Interleucina-4/genética , Interleucina-4/metabolismo , Adulto , Periodontite Crônica/terapia , Feminino , Líquido do Sulco Gengival/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
14.
Pathog Dis ; 69(1): 21-28, 2013 10.
Artigo em Inglês | MEDLINE | ID: mdl-23821559

RESUMO

The aim of this study was to investigate the effect of non-surgical treatment of periodontitis on the levels of periodontopathogens and clinical parameters in patients with different genetic backgrounds produced by polymorphisms in the Interleukin ( IL8) gene. Thirty patients grouped according to IL8 ATC/TTC or AGT/TTC haplotypes were submitted to non-surgical periodontal treatment. Levels of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola were determined in 240 subgingival plaque samples by qPCR. The association between IL8 haplotypes and the levels of periodontopathogens and clinical parameters was investigated by multilevel analysis accounting for the clustering of diseased sites analyzed within patients. It was observed that neither levels of periodontopathogens nor non-surgical treatment was associated with the IL8 haplotype. The clinical parameters after periodontal treatment were similar in diseased and healthy sites, independently of the IL8 haplotype. Nonetheless, in the same period, diseased sites of AGT/TTC patients harbored higher levels of P. gingivalis, T. denticola, T. forsythia, and red complex than those of ATC/TTC patients. However, the non-surgical periodontal therapy decreased the levels of these periodontopathogens and of the tested clinical parameters of diseased sites in both groups. Non-surgical therapy is equally effective in improving clinical parameters and decreasing the levels of periodontopathogens, independent of the genotype groups produced by the IL8 haplotype.


Assuntos
Carga Bacteriana , Predisposição Genética para Doença , Interleucina-8/genética , Periodontite/genética , Porphyromonas gingivalis/isolamento & purificação , Tannerella forsythia/isolamento & purificação , Treponema denticola/isolamento & purificação , Placa Dentária/microbiologia , Haplótipos , Humanos , Periodontite/microbiologia , Periodontite/patologia , Periodontite/terapia , Reação em Cadeia da Polimerase em Tempo Real , Resultado do Tratamento
15.
Arch Oral Biol ; 57(10): 1355-61, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22877792

RESUMO

OBJECTIVE: Previously, we identified that the ATC/TTC haplotype formed by polymorphisms in the Interleukin-(IL)8 gene conferred susceptibility to chronic periodontitis (CP). The aim of the study was to investigate whether the IL8 haplotype ATC/TTC was associated with the volume of gingival crevicular fluid (GCF), the concentration of interleukin IL-8 in the GCF, as well as periodontal conditions in patients with CP in comparison to controls without CP. METHODS: Seventy-nine individuals (CP: n=41, controls: n=38) were grouped according to the presence (susceptible for CP) or absence (not susceptible for CP) of the IL8 ATC/TTC haplotype. After periodontal clinical evaluation, they were subdivided by the presence or absence of CP. GCF was collected from each patient and the IL-8 levels were determined by ELISA. The GCF volume of each subject was measured by means of a calibrated electronic device. Comparisons of means between carriers and non-carriers of the ATC/TTC haplotype were evaluated using the Mann-Whitney test. Linear regression and stepwise linear regression analysis were used to analyse the association of the GCF volume with potential covariates and their contribution for the phenotype. RESULTS: We did not find significant differences of both periodontal conditions and IL-8 concentration in the GCF of patients with the presence or absence of the IL8 ATC/TTC haplotype. However, the GCF volume was significantly higher amongst the patients affected by CP that are absent for the IL8 ATC/TTC haplotype. In addition, linear regression analysis showed a statistically significant association between GCF volume and CP, IL8 haplotype ATC/TTC and IL-8 concentration. CONCLUSIONS: The IL8 haplotype of susceptibility to CP was neither associated with IL-8 cytokine levels nor with clinical periodontal parameters. Also, CP, IL8 haplotype and IL-8 concentration showed a positive association with the GCF volume levels in the studied patients.


Assuntos
Periodontite Crônica/genética , Líquido do Sulco Gengival/química , Haplótipos , Interleucina-8/genética , Proteínas/química , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Ensaio de Imunoadsorção Enzimática , Feminino , Predisposição Genética para Doença , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fenótipo , Estatísticas não Paramétricas
16.
Arch Oral Biol ; 57(9): 1256-63, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22425265

RESUMO

OBJECTIVE: Three single nucleotide polymorphisms (SNPs), -1082, -819 and -592, located on the promoter region of IL10 gene have been associated with high in vitro IL-10 production and autoimmune diseases. We aim to investigate whether polymorphisms in the IL10 gene would influence dental implant loss. METHODS: We evaluated a total of 277 unrelated patients, including 185 individuals presenting at least one osseointegrated implant in function for six months or more and with no implant failure, and 92 individuals presenting at least one implant loss. DNA was extracted from buccal mucosa cells and SNPs were genotyped using TaqMan(®) probes-based assays. RESULTS: Multiple logistic regression showed association between dental implant failure with -819(C/T) genotype (OR=3.27; 95% CI=1.02-10.46; p=0.0334). However, considering the statistical significance level α=0.004 (adjusted by Bonferroni correction of multiple comparisons), these results lost their significance. No association of dental implant loss with genotypes and alleles of the -1082 and -592 SNPs, as well as IL10 haplotypes in genotype/allele forms were found (p=0.9400; p=0.8861). CONCLUSIONS: Neither the IL10 gene polymorphisms, nor haplotypes or other covariates were associated with susceptibility to dental implant failure in the studied population.


Assuntos
Implantes Dentários , Falha de Restauração Dentária , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único/genética , Adenina , Alelos , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Doenças Cardiovasculares/complicações , Estudos de Casos e Controles , Citosina , Feminino , Predisposição Genética para Doença/genética , Genótipo , Guanina , Haplótipos/genética , Humanos , Hipertensão/complicações , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Osseointegração/fisiologia , Regiões Promotoras Genéticas/genética , Doenças Reumáticas/complicações , Fumar , Timina
17.
Acta Odontol Latinoam ; 24(3): 283-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22550823

RESUMO

A study was performed to evaluate the influence of mandibular lateral excursion, group function and canine guidance on vestibular cervical dental abfraction (VCDA). Thirty-six individuals of both sexes, aged 20 to 45 years, with full natural dentition with at least one tooth with VCDA were selected at the San Marcos University Clinic. We evaluated number of teeth with VCDA per side (left and right), tooth type and lateral excursive movement (canine guidance or group function) affecting it. The results showed no statistical difference (p > 0.05). The tooth type most often showing VCDA was the first lower premolar, with 30.8% on the right side and 36.4% on the left. Moderate positive correlation was found between age and VCDA (R = 0.40). It is concluded that group function during lateral excursion may contribute to presence of VCDA.


Assuntos
Mandíbula/fisiologia , Desgaste dos Dentes , Adulto , Oclusão Dentária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Acta odontol. latinoam ; 24(3): 283-288, 2011. tab, graf
Artigo em Inglês | LILACS | ID: lil-668290

RESUMO

Se realizó una investigación para evaluar la influencia de los movimientos excursivos laterales mandibulares; función de grupo y guía canina sobre abfracción dentaria cervico vestibular(ADCV). Se seleccionaron 36 individuos de ambos sexos entre 20 a 45 años de edad, con dentición natural completaque presentan como mínimo un diente con ADCV, en la Clínica Universitaria de la UNMSM. Se evaluó el número de dientes con ADCV por cada lado (derecho e izquierdo), tipo de diente,y movimiento excursivo lateral (guia canina o función en grupo) que lo influye. Los resultados denotaron no significancia estadísticas (p>0,05), el tipo de diente con mayor frecuencia a presentar ADCV fue el primer premolar inferior, 30,8 por ciento del lado derecho y 36,4 por ciento del lado izquierdo. Se encontró correlación positiva moderada entre edad y ADCV(r=0,40). Se concluye que la excursion lateral función en grupo puede contribuir a la presencia de ADCV.


Assuntos
Humanos , Colo do Dente/patologia , Atrito Dentário , Doenças Dentárias/classificação , Oclusão Dentária , Fatores de Risco
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