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1.
J Appl Oral Sci ; 28: e20190140, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31800874

RESUMO

OBJECTIVE: The goal of the present study was to determine the effect of systemic and topical ozone application on alveolar bone loss (ABL) by evaluating the effect of Hypoxia-inducible factor -1 alpha (HIF-1-α) and receptor activator of NF-kB ligand (RANKL)-positive cells on histopathological and immunohistochemical changes in a rat periodontitis model. METHODOLOGY: Thirty male Wistar rats were divided into three groups: 1) Group C (control group); 2) Group SO (systemic ozone group) and 3) Group TO (topical ozone group). Experimental periodontitis was induced with a 3/0 silk suture placed at the mandibular left first molars of rats, and the suture was removed 14 days later. Ozone gas was injected intraperitoneally (0.7 mg/kg) in SO group. Topical ozone application protocol was performed using an ozone generator at 80% concentration (4th grade) 90- degree probe for the duration of 30 s. Both ozone applications were carried out for two weeks at intervals of two days. Histomorphometric and immunohistochemical analysis were performed. RESULTS: ABL was significantly lower in Group SO compared to Group C (p: 0.0052). HIF-1α- positive cells were significantly lower in Group TO than in Group C (p: 0.0043). RANKL-positive cells were significantly lower in Group SO and in Group TO compared to the control group (p: 0.0033, p: 0.0075, respectively). CONCLUSION: Both ozone applications decreased RANKL-positive cell counts, TO application decreased HIF-1-α positive cells counts, and SO application was found to be more effective in reducing ABL compared to control group.


Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Ozônio/administração & dosagem , Periodontite/tratamento farmacológico , Periodontite/patologia , Administração Tópica , Animais , Contagem de Células , Imuno-Histoquímica , Masculino , Ligante RANK/análise , Ratos Wistar , Reprodutibilidade dos Testes , Resultado do Tratamento
2.
Adv Exp Med Biol ; 1197: 45-54, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31732933

RESUMO

New strategies are critically needed to counter uncontrolled periodontal infection and inflammation in obesity-associated type 2 diabetes (T2D). However, mechanisms that explain the relationship between periodontitis (PD) and T2D remain poorly understood. Several lines of evidence indicate that destructive immune responses potentiate periodontitis (PD) in T2D. B cells are abundant in periodontal lesions, and our data show that B cells are required for PD in obese/insulin resistant but not lean/normoglycemic mice. In mice and in people, T2D-primed B cells supported Th17 cytokine profiles, but B cells had a modest effect on T-cell function in samples from normoglycemic individuals. Given the recently appreciated importance of Th17 cells in PD outside a T2D milieu, our data raise the possibility that B cells indirectly promote T2D-potentiated PD through support of Th17 cells, which in turn directly promote PD.Data herein thereby suggest unexpected mechanisms that explain the clinical observation that T2D potentiates PD.


Assuntos
Diabetes Mellitus Tipo 2 , Periodontite , Células Th17 , Animais , Diabetes Mellitus Tipo 2/complicações , Inflamação , Camundongos , Obesidade/fisiopatologia , Periodontite/complicações , Periodontite/patologia , Células Th17/citologia
3.
J Appl Oral Sci ; 27: e20180602, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31508794

RESUMO

OBJECTIVE: This study aimed to evaluate the effect of avocado/soybean unsaponifiables (ASU) on periodontal repair in rats with induced periodontitis and arthritis. METHODOLOGY: Forty-five rats were submitted to periodontitis induction by insertion of ligatures into the upper second molars, maintained for 15 days. These animals were randomly allocated to 3 groups according to the presence of induced arthritis (ART) and the application of the ASU: Control (CTR) group-healthy animals, where saline solution was administered; ART-animals with induced arthritis, where saline solution was administered; ART/ASU-animals with induced arthritis, where ASU (0.6 mg/ kg) was administered. The drugs were administered daily by gavage and the animals were euthanized after 7, 15 and 30 days of the ligature removal. Bone resorption, inflammatory infiltrate composition and marker proteins expression of the differentiation and formation of osteoclasts (RANKL and TRAP) were assessed. RESULTS: The ART/ASU group presented higher bone volume than the ART group at 7 and 30 days after the ligature removal. Furthermore, the ART group presented higher quantity of inflammatory cells and expression of TRAP and RANKL than the other groups. CONCLUSION: ASU administration improves the repair of periodontal tissues in an experimental periodontitis model in rats with induced arthritis.


Assuntos
Artrite/tratamento farmacológico , Periodontite/tratamento farmacológico , Persea/química , Extratos Vegetais/farmacologia , Soja/química , Animais , Artrite/patologia , Imuno-Histoquímica , Masculino , Periodontite/patologia , Ligante RANK/análise , Distribuição Aleatória , Ratos , Reprodutibilidade dos Testes , Fosfatase Ácida Resistente a Tartarato/análise , Fatores de Tempo , Resultado do Tratamento , Microtomografia por Raio-X
4.
J Appl Oral Sci ; 27: e20180671, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31508795

RESUMO

OBJECTIVE: To monitor early periodontal disease progression and to investigate clinical and molecular profile of inflamed sites by means of crevicular fluid and gingival biopsy analysis. METHODOLOGY: Eighty-one samples of twenty-seven periodontitis subjects and periodontally healthy individuals were collected for the study. Measurements of clinical parameters were recorded at day -15, baseline and 2 months after basic periodontal treatment aiming at monitoring early variations ofthe clinical attachment level. Saliva, crevicular fluid and gingival biopsies were harvested from clinically inflamed and non-inflamed sites from periodontal patients and from control sites of healthy patients for the assessment of IL-10, MMP-8, VEGF, RANKL, OPG and TGF-ß1 protein and gene expression levels. RESULTS: Baseline IL-10 protein levels from inflamed sites were higher in comparison to both non-inflamed and control sites (p<0.05). Higher expression of mRNA for IL-10, RANK-L, OPG, e TGF-ß1 were also observed in inflamed sites at day -15 prior treatment (p<0.05). After the periodontal treatment and the resolution of inflammation, seventeen percent of evaluated sites still showed clinically detectable attachment loss without significant differences in the molecular profile. CONCLUSIONS: Clinical attachment loss is a negative event that may occur even after successful basic periodontal therapy, but it is small and limited to a small percentage of sites. Elevated inflammation markers of inflamed sites from disease patients reduced to the mean levels of those observed in healthy subjects after successful basic periodontal therapy. Significantly elevated both gene and protein levels of IL-10 in inflamed sites prior treatment confirms its modulatory role in the disease status.


Assuntos
Perda da Inserção Periodontal/patologia , Periodontite/patologia , Adulto , Biomarcadores/análise , Biópsia , Estudos de Casos e Controles , Citocinas/análise , Feminino , Gengiva/patologia , Líquido do Sulco Gengival/química , Humanos , Masculino , Metaloproteinase 8 da Matriz/análise , Pessoa de Meia-Idade , Osteoprotegerina/análise , Periodontite/terapia , Reação em Cadeia da Polimerase em Tempo Real , Saliva/química , Estatísticas não Paramétricas , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/análise
5.
Oxid Med Cell Longev ; 2019: 1529520, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485288

RESUMO

Aim: To investigate whether methylene blue-mediated photodynamic therapy (MB-PDT) can affect the "fate" of macrophages in vitro or in periodontitis tissues and to explore the potential mechanism. Methods: For in vitro treatments, THP-1 macrophages were divided into three experimental groups: C/control, no treatment; MB, methylene blue treatment; and MB-PDT, MB and laser irradiation treatment. Then, apoptosis and apoptosis-related proteins were detected in each group. For in vivo treatments, periodontitis was ligature-induced in the first molars of the bilateral maxilla in 12 Sprague Dawley (SD) rats. After six weeks, the ligatures were removed and all the induced molars underwent scaling and root planning (SRP). Then, the rats were divided into three groups according to the following treatments: SRP, saline solution; MB, phenothiazinium dye; and MB-PDT, MB and laser irradiation. Apoptotic macrophages, inflammation levels, and alveolar bone resorption in the periodontal tissues of rats were analyzed in each group. Results: In vitro, flow cytometry analysis demonstrated that 10 µM MB and 40 J/cm2 laser irradiation maximized the apoptosis rate (34.74%) in macrophages. Fluorescence probe and Western blot analyses showed that MB-PDT induced macrophage apoptosis via reactive oxygen species (ROS) and the mitochondrial-dependent apoptotic pathway. Conversely, the addition of exogenous antioxidant glutathione (GSH) and the pan-caspase inhibitor Z-VAD-FMK markedly reduced the apoptotic response in macrophages. In vivo, immunohistochemistry, histology, radiographic, and molecular biology experiments revealed fewer infiltrated macrophages, less bone loss, and lower IL-1ß and TNF-α levels in the MB-PDT group than in the SRP and MB groups (P < 0.05). Immunohistochemistry analysis also detected apoptotic macrophages in the MB-PDT group. Conclusion: MB-PDT could induce macrophage apoptosis in vitro and in rats with periodontitis. This may be another way for MB-PDT to relieve periodontitis in addition to its antimicrobial effect. Meanwhile, MB-PDT induced apoptosis in THP-1 macrophages via the mitochondrial caspase pathway.


Assuntos
Perda do Osso Alveolar/metabolismo , Macrófagos/metabolismo , Periodontite/terapia , Fotoquimioterapia/métodos , Animais , Apoptose , Masculino , Azul de Metileno , Periodontite/patologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio
6.
Infect Immun ; 87(10)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31331955

RESUMO

Porphyromonas gingivalis is considered a keystone pathogen that contributes to the initiation and progression of periodontitis in humans. P. gingivalis has also been detected in human placentas associated with adverse pregnancy outcomes. The spread of P. gingivalis from the oral cavity to the reproductive tract thus represents a potential mechanism whereby periodontitis can lead to adverse pregnancy outcomes. In a murine model of pregnancy and oral infection with P. gingivalis, C57BL/6J mice developed low fetal weight, whereas C57BL/6NCrl mice did not. Although C57BL/6NCrl mice harbor segmented filamentous bacteria that drive a Th17 response, fetal weight was independent of frequency of Th17 or Th1 in either substrain. Low fetal weight was instead correlated with increasing amounts of P. gingivalis DNA in the placentas of the C57BL/6J dams. In contrast, fetal weight in C57BL/6NCrl mice was independent of P. gingivalis in the placenta. Differences in genetics or microbiome that influence the ability of P. gingivalis to colonize the placenta may drive differential fetal weight outcomes between C57BL/6J and C57BL/6NCrl mice and, potentially, between diverse human populations.


Assuntos
Infecções por Bacteroidaceae/microbiologia , Peso Fetal , Periodontite/microbiologia , Porphyromonas gingivalis/patogenicidade , Complicações Infecciosas na Gravidez/microbiologia , Células Th17/microbiologia , Animais , Infecções por Bacteroidaceae/imunologia , Infecções por Bacteroidaceae/patologia , Modelos Animais de Doenças , Feminino , Feto , Expressão Gênica , Interferon gama/genética , Interferon gama/imunologia , Interleucina-17/genética , Interleucina-17/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Boca/imunologia , Boca/microbiologia , Periodontite/imunologia , Periodontite/patologia , Placenta/imunologia , Placenta/microbiologia , Porphyromonas gingivalis/imunologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/patologia , Especificidade da Espécie , Células Th17/imunologia
7.
Int J Oral Sci ; 11(3): 21, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31257363

RESUMO

Growing evidence suggests close associations between periodontitis and atherosclerosis. To further understand the pathological relationships of these associations, we developed periodontitis with ligature placement around maxillary molars or ligature placement in conjunction with Porphyromonas gingivalis lipopolysaccharide injection at the ligature sites (ligature/P.g. LPS) in Apolipoprotein E knock out mice and studied the atherogenesis process in these animals. The mice were fed with high fat diet for 11 weeks and sacrificed for analyzing periodontitis, systemic inflammation, and atherosclerosis. Controls did not develop periodontitis or systemic inflammation and had minimal lipid deposition in the aortas, but mice receiving ligature or ligature/P.g. LPS showed severe periodontitis, systemic inflammation, and aortic plaque formation. The aortic plaque contained abundant macrophages and cells expressing both endothelial and mesenchymal cell markers. The severity of periodontitis was slightly higher in mice receiving ligature/P.g. LPS than ligature alone, and the magnitude of systemic inflammation and aortic plaque formation were also notably greater in the mice with ligature/P.g. LPS. These observations indicate that the development of atherosclerosis is due to systemic inflammation caused by severe periodontitis. In vitro, P.g. LPS enhanced the secretion of pro-inflammatory cytokines from macrophages and increased the adhesion of monocytes to endothelial cells by upregulating the expression of adhesion molecules from endothelial cells. Moreover, secretory proteins, such as TNF-α, from macrophages induced endothelial-mesenchymal transitions of the endothelial cells. Taken together, systemic inflammation induced by severe periodontitis might exacerbate atherosclerosis via, in part, causing aberrant functions of vascular endothelial cells and the activation of macrophages in mice.


Assuntos
Aterosclerose/imunologia , Inflamação , Periodontite/imunologia , Periodontite/fisiopatologia , Animais , Aterosclerose/patologia , Modelos Animais de Doenças , Células Endoteliais , Lipopolissacarídeos/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Periodontite/patologia , Porphyromonas gingivalis
8.
Oral Dis ; 25(8): 1972-1982, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31361069

RESUMO

OBJECTIVE: Macrophages could be fully polarized and acquire specific phenotype like M1, which considered to be essential for the alveolar bone destruction during the development of periodontitis. However, the molecular mechanisms underlying the effects of M1 macrophages on the alveolar bone destruction are still not clear yet. METHODS: Mouse periodontitis model was established to determine the involvement of M1 macrophages in the pathogenic process. Condition medium of the M1 macrophages (M1-CM) was incubated with pre-osteoblasts to evaluate its effects on the osteoblastogenesis. Cells after treatment with CM were used for RNA-sequencing, quantitative PCR, Western blotting, and immunofluorescence staining to figure out pathways involved in the inhibition of osteoblastogenesis. RESULTS: Increased infiltration of M1 macrophages was associated with alveolar bone destruction in periodontitis. M1-CM markedly suppressed the generation of osteoblasts as evidenced by decreased expressions of Runx2 and Ocn, as well as reduced activity of ALP. Interestingly, RNA-sequencing indicated the activation of TLR4/AP1 signaling pathway in pre-osteoblasts treated with CM. Inhibition of TLR4 reduced the translocation of AP1 and rescued the osteoblastogenesis reduced by M1-CM. CONCLUSION: M1 macrophages induce TLR4/AP1 signaling of pre-osteoblasts to inhibit the osteoblastogenesis via paracrine, at least partially contributing to alveolar bone destruction in periodontitis.


Assuntos
Perda do Osso Alveolar , Macrófagos/metabolismo , Periodontite , Receptor 4 Toll-Like , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/patologia , Animais , Camundongos , Osteoblastos , Periodontite/tratamento farmacológico , Periodontite/patologia , Transdução de Sinais
9.
Biomed Res Int ; 2019: 7984891, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355282

RESUMO

Objective: The present study aimed to compare variations in quantified tumor necrosis factor-alpha (TNF-α) levels in patients with periodontitis stage 2 grade B (POD2B) and/or type 2 diabetes (T2D) and to identify any relationships between this cytokine and these diseases. Methods: Levels of the cytokine TNF-α in gingival crevicular fluid in patients with POD2B and/or T2D were evaluated. A total of 160 subjects were distributed into four groups: those with POD2B (n=44); those with T2D (n=37); those with POD2B/T2D (n=40); and healthy subjects (n=39). Glycosylated hemoglobin (HbA1c) and blood glucose (BG) levels were quantified in each subject. Data were collected on body mass index (BMI), loss of insertion (LI), and probe depth (PD). Gingival crevicular fluid samples were collected from the most acutely affected periodontal pocket and gingival sulcus in each subject, and TNF-α was quantified by multiplex analysis. Results: Kruskal Wallis tests was used to identify differences in TNF-α levels, LI, PD, BMI, BG, and HbA1c by group. Differences (p<0.001) were found for LI, PD, BG, and HbA1c. A Spearman test was used to calculate possible correlations between TNF-α levels and LI or PD identified a weak but significant negative correlation of TNF-α with LI (Rho=-0199; p=0.012), and a moderately positive correlation of LI with PD (Rho=0.509; p < 0.001). Conclusions: No variation was found between TNF-α levels and the presence of POD2B, POD2B/T2D, or T2D, suggesting the absence of any direct relationship between progression of these diseases and TNF-α levels. However, a correlation was present between low TNF-α concentrations and greater LI.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Bolsa Periodontal/sangue , Periodontite/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto , Índice de Massa Corporal , Índice de Placa Dentária , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Progressão da Doença , Feminino , Gengiva/metabolismo , Gengiva/patologia , Líquido do Sulco Gengival/metabolismo , Hemoglobina A Glicada/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Bolsa Periodontal/complicações , Bolsa Periodontal/patologia , Periodontite/complicações , Periodontite/patologia
10.
Cells ; 8(6)2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31167434

RESUMO

Periodontitis is a prevalent infectious disease worldwide, causing the damage of periodontal support tissues, which can eventually lead to tooth loss. The goal of periodontal treatment is to control the infections and reconstruct the structure and function of periodontal tissues including cementum, periodontal ligament (PDL) fibers, and bone. The regeneration of these three types of tissues, including the re-formation of the oriented PDL fibers to be attached firmly to the new cementum and alveolar bone, remains a major challenge. This article represents the first systematic review on the cutting-edge researches on the regeneration of all three types of periodontal tissues and the simultaneous regeneration of the entire bone-PDL-cementum complex, via stem cells, bio-printing, gene therapy, and layered bio-mimetic technologies. This article primarily includes bone regeneration; PDL regeneration; cementum regeneration; endogenous cell-homing and host-mobilized stem cells; 3D bio-printing and generation of the oriented PDL fibers; gene therapy-based approaches for periodontal regeneration; regenerating the bone-PDL-cementum complex via layered materials and cells. These novel developments in stem cell technology and bioactive and bio-mimetic scaffolds are highly promising to substantially enhance the periodontal regeneration including both hard and soft tissues, with applicability to other therapies in the oral and maxillofacial region.


Assuntos
Cemento Dentário/fisiologia , Ligamento Periodontal/fisiologia , Regeneração/fisiologia , Células-Tronco/metabolismo , Terapia Genética , Humanos , Periodontite/patologia , Periodontite/terapia , Transplante de Células-Tronco , Células-Tronco/citologia , Engenharia Tecidual , Tecidos Suporte/química
11.
BMC Res Notes ; 12(1): 328, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182149

RESUMO

OBJECTIVE: The aim of the present study is to compare and assess the risk of periodontitis due to the presence of four putative periodontopathic bacteria viz., Eikenella corrodens, Campylobacter rectus, Prevotella intermedia and Prevotella nigrescens. To fulfil the above objective, polymerase Chain reaction using the primers targeting 16S rRNA gene of the bacterial species was performed with the subgingival plaque collected from the permanent first molars of type 1 diabetic children and age matched healthy children. RESULTS: The prevalence of periodontal pathogens in diabetic and healthy children was 6% and 16% for E. corrodens, 18% and 36% for C. rectus, 2% and 2% for P. intermedia, 4% and 0%, for P. nigrescens respectively. Statistically, significant difference was not observed for the prevalence of all the four periodontal pathogens between type 1 diabetic and healthy children (P = 1.00). The results of the present study thus reveal a negative correlation of type I diabetes to periodontitis in association to Eikenella corrodens, Campylobacter rectus, Prevotella intermedia and Prevotella nigrescens.


Assuntos
Campylobacter rectus/genética , Placa Dentária/microbiologia , Diabetes Mellitus Tipo 1/microbiologia , Eikenella corrodens/genética , Periodontite/microbiologia , Prevotella intermedia/genética , Prevotella nigrescens/genética , Adolescente , Técnicas de Tipagem Bacteriana , Campylobacter rectus/classificação , Campylobacter rectus/isolamento & purificação , Estudos de Casos e Controles , Criança , Placa Dentária/complicações , Placa Dentária/diagnóstico , Placa Dentária/patologia , Índice de Placa Dentária , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/patologia , Eikenella corrodens/classificação , Eikenella corrodens/isolamento & purificação , Feminino , Humanos , Masculino , Periodontite/complicações , Periodontite/diagnóstico , Periodontite/patologia , Prevotella intermedia/classificação , Prevotella intermedia/isolamento & purificação , Prevotella nigrescens/classificação , Prevotella nigrescens/isolamento & purificação , RNA Ribossômico 16S/genética
12.
Indian J Med Res ; 149(3): 364-368, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31249201

RESUMO

Background & objectives: : There is a paucity of information on association between dental fluorosis, osteoporosis and periodontitis. The aim of this pilot study was to evaluate oestrogen receptor (ER). Rsa 1: gene polymorphism in osteoporosis periodontitis patients with and without dental fluorosis. Methods: : Twenty one primary osteoporotic patients suffering from periodontitis with dental fluorosis and 20 primary osteoporotic patients suffering from periodontitis without dental fluorosis participated in this study. Periodontitis was diagnosed based on age, gender T-scores using clinical parameters such as plaque scores, gingival bleeding scores and probing pocket depth, clinical attachment level (CAL) and severity of dental fluorosis. DNA was genotyped at the RsaI RFLP (in exon 5) inside the ER gene to study ER Rsa I gene polymorphism in osteoporosis periodontitis patients with and without dental fluorosis. Results: : Patients with dental fluorosis had higher degree of osteoporosis than those without fluorosis. CAL was significantly higher (P <0.05) in those with dental fluorosis compared with those without. Rr heterozygote (21.95%) was observed in patients without fluorosis whereas RR mutant homozygote was absent in both the groups. Rr wild homozygote type was seen more in the patients with fluorosis (51.21%). Significant differences were found in distribution of these genotypes between patients with and without dental fluorosis. Interpretation & conclusions: : This preliminary study showed the presence of ER I gene polymorphism in osteoporosis periodontitis patients without dental fluorosis. Further studies with large sample size are needed to confirm the association shown in this preliminary study.


Assuntos
Receptor alfa de Estrogênio/genética , Fluorose Dentária/genética , Osteoporose/genética , Periodontite/genética , Adulto , Idoso , Desoxirribonucleases de Sítio Específico do Tipo II/genética , Feminino , Fluorose Dentária/epidemiologia , Fluorose Dentária/patologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/patologia , Periodontite/epidemiologia , Periodontite/patologia
13.
Braz Oral Res ; 33: e025, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31038565

RESUMO

Recently, it has been suggested that the anti-inflammatory hormone ghrelin (GHRL) and its receptor GHS-R may play a pivotal role in periodontal health and diseases. However, their exact regulation and effects in periodontitis are not known. The aim of this in-vitro study was to investigate the effect of microbial and inflammatory insults on the GHS-R1a expression in human osteoblast-like cells. MG-63 cells were exposed to interleukin (IL)-1ß and Fusobacterium nucleatum in the presence and absence of GHRL for up to 2 d. Subsequently, gene expressions of GHS-R1a, inflammatory mediators and matrix metalloproteinase were analyzed by real-time PCR. GHS-R protein synthesis and NF-κB p65 nuclear translocation were assessed by immunocytochemistry and immunofluorescence microscopy, respectively. IL-1ß and F. nucleatum caused a significant upregulation of GHS-R1a expression and an increase in GHS-R1a protein. Pre-incubation with a MEK1/2 inhibitor diminished the IL-1ß-induced GHS-R1a upregulation. IL-1ß and F. nucleatum also enhanced the expressions of cyclooxygenase 2, CC-chemokine ligand 2, IL-6, IL-8, and matrix metalloproteinase 1, but these stimulatory effects were counteracted by GHRL. By contrast, the stimulatory actions of IL-1ß and F. nucleatum on the GHS-R1a expression were further enhanced by GHRL. Our study provides original evidence that IL-1ß and F. nucleatum regulate the GHS-R/GHRL system in osteoblast-like cells. Furthermore, we demonstrate for the first time that the proinflammatory and proteolytic actions of IL-1ß and F. nucleatum on osteoblast-like cells are inhibited by GHRL. Our study suggests that microbial and inflammatory insults upregulate GHS-R1a, which may represent a protective negative feedback mechanism in human bone.


Assuntos
Fusobacterium nucleatum/fisiologia , Interleucina-1beta/farmacologia , Osteoblastos/química , Receptores de Grelina/análise , Análise de Variância , Células Cultivadas , Humanos , Imuno-Histoquímica , Microscopia de Fluorescência , Osteoblastos/efeitos dos fármacos , Osteoblastos/microbiologia , Periodontite/microbiologia , Periodontite/patologia , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Grelina/fisiologia , Estatísticas não Paramétricas , Regulação para Cima/fisiologia
14.
Braz Oral Res ; 33: e032, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31038567

RESUMO

This study aimed to investigate the effects of astragaloside IV (AsIV) on inflammation and immunity in rats with experimental periodontitis. Periodontitis was established in 48 Wistar rats, which were then randomly divided into model and 10, 20 and 40 mg/kg AsIV groups, with 12 rats in each group. The latter 3 groups were treated with AsIV at doses of 10, 20 and 40 mg/kg, respectively. The control group (12 rats, without periodontitis) and model group were given the same amount of 5% sodium carboxymethyl cellulose. The treatment was performed once per day for 8 weeks. Before and after treatment, the tooth mobility scores of the rats were determined. After treatment, the salivary occult blood index (SOBI), plaque index (PLI), peripheral blood T lymphocyte subsets, and serum inflammatory factor and immunoglobulin levels were determined. The results showed that, after treatment, compared with that in model group, in 40 mg/kg AsIV group, the general state of rats was improved, while the tooth mobility score, SOBI and PLI were significantly decreased (p < 0.05); the peripheral blood CD4+ T cell percentage and CD4+/CD8+ ratio were significantly increased (p < 0.05), while the CD8+ T cell percentage was significantly decreased (p < 0.05); the serum tumor necrosis factor-α, interleukin-1ß and interleukin-2 levels were significantly decreased (p < 0.05); the serum immunoglobulin A and immunoglobulin G levels were significantly decreased (p < 0.05). In conclusion, AsIV can alleviate inflammation and enhance immunity in rats with experimental periodontitis.


Assuntos
Sistema Imunitário/efeitos dos fármacos , Periodontite/tratamento farmacológico , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Feminino , Imunoglobulinas/sangue , Interleucina-1beta/sangue , Interleucina-2/sangue , Masculino , Periodontite/imunologia , Periodontite/patologia , Distribuição Aleatória , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Subpopulações de Linfócitos T , Mobilidade Dentária , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue
15.
Mol Med Rep ; 19(6): 4743-4752, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059030

RESUMO

Interleukin 17A (IL­17A) exerts pleiotropic effects on periodontitis, partially through enhancement of alveolar bone loss. Osteoclasts are the main culprits that absorb alveolar bone. However, studies describing the correlation between IL­17A and osteoclasts are not conclusive. Previously, autophagy was revealed to be involved in osteoclast differentiation and bone resorption. However, the role of autophagy in IL­17A­mediated osteoclast formation is yet to be clarified. In the present study, bone marrow macrophages (BMMs) were treated with or without IL­17A. 3­Methyladenine (3­MA) was applied to inhibit autophagy. Osteoclast formation was detected by tartrate­resistant acid phosphatase (TRAP) staining, immunofluorescence, and scanning electron microscope. The effects of IL­17A on osteoclast­specific genes and autophagy­related genes during osteoclast differentiation were examined by real­time quantitative polymerase chain reaction and western blot analysis. Autophagosomes were observed by transmission electron microscope. Hematoxylin and eosin (H&E), and TRAP staining was adopted to assess alveolar bone destruction and the number of osteoclasts, respectively in a rat periodontitis model. Consequently, IL­17A stimulated osteoclast differentiation and bone resorption of BMMs accompanied by an increase in the mRNA expression of osteoclast­specific genes. Furthermore, IL­17A increased the levels of autophagy­related genes and proteins, and inhibition of autophagy with 3­MA attenuated the IL­17A­mediated osteoclastogenesis. In addition, there was an increase in the number of osteoclasts and alveolar bone resorption with IL­17A treatment in the periodontitis rat model. Collectively, these findings indicated that IL­17A facilitated osteoclast differentiation and bone resorption in vitro and in vivo, which may contribute to the understanding of the molecular basis of IL­17A in alveolar bone destruction and provide insight on the clinical therapeutic targets for periodontitis.


Assuntos
Autofagia/efeitos dos fármacos , Medula Óssea/metabolismo , Reabsorção Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Interleucina-17/farmacologia , Macrófagos/metabolismo , Osteoclastos/metabolismo , Actinas/metabolismo , Adenina/análogos & derivados , Adenina/antagonistas & inibidores , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/patologia , Animais , Autofagossomos/patologia , Autofagia/genética , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Reabsorção Óssea/patologia , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Periodontite/tratamento farmacológico , Periodontite/patologia , Ratos , Ratos Sprague-Dawley
16.
Artif Cells Nanomed Biotechnol ; 47(1): 2098-2106, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31144533

RESUMO

Periodontitis refers to the inflammation of gums and the surrounding structures and caused by a bacterial infection. The infection occurs owing to poor oral hygiene and could destroy the bone and the gum over time if left untreated. The present study identified the involvement of a key long noncoding RNA (lncRNA), i.e. FGD5-AS1, in the pathogenesis of periodontitis by assessing its expression in the gingival tissues of patients diagnosed with chronic periodontitis (CP). Overexpression of FGD5-AS1 in primary human periodontal ligament cells (PDLCs) significantly reduced the lipopolysaccharide (LPS)-induced periodontitis, whereas its suppression aggravated this injury. Moreover, the miR-142-3p was markedly expressed in the gingival samples of patients diagnosed with CP and LPS-induced PDLCs. We found that the FGD5-AS1-mediated reduction in the inflammation was mediated through downside regulation of miR-142-3p, as evident from the upregulation of SOCS6, a target gene of miR-142-3p. Furthermore, the association between FGD5-AS1 and NF-κB pathway was detected. FGD5-AS1 was found to protect against LPS-stimulated PDLC injury through restraining the NF-κB signals. Based on these findings, we conclude that up-regulation of lncRNA FGD5-AS1 could protect against periodontitis via regulating the miR-142-3p/SOCS6/NF-κB signals. Therefore, the FGD5-AS1/miR-142-3p/SOCS6 axis may act as an important indicator in explaining the pathogenesis of periodontitis.


Assuntos
Regulação da Expressão Gênica , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Periodontite/genética , Periodontite/metabolismo , RNA Longo não Codificante/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Estudos de Casos e Controles , Gengiva/metabolismo , Gengiva/patologia , Humanos , MicroRNAs/genética , Periodontite/patologia , Transdução de Sinais/genética , Regulação para Cima
17.
Korean J Gastroenterol ; 73(5): 285-293, 2019 May 25.
Artigo em Coreano | MEDLINE | ID: mdl-31132835

RESUMO

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract with an unknown etiology and pathogenesis. The incidence and prevalence of IBD are increasing rapidly in Korea. Approximately one-third of patients with IBD appear to develop extra-intestinal manifestations with the skin being one of the most commonly affected organs. They may precede, occur simultaneously, or follow the diagnosis of IBD. In addition, they may parallel with the luminal symptoms or independent from the disease activity of IBD. This review outlines the skin manifestations associated with IBD and discusses their management. Skin manifestations should be managed in close collaboration with a dermatologist.


Assuntos
Doenças Inflamatórias Intestinais/patologia , Dermatopatias/patologia , Eritema/complicações , Eritema/tratamento farmacológico , Eritema/patologia , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/complicações , Periodontite/complicações , Periodontite/patologia , Psoríase/complicações , Psoríase/patologia , Pioderma Gangrenoso/complicações , Pioderma Gangrenoso/tratamento farmacológico , Pioderma Gangrenoso/patologia , Dermatopatias/complicações , Esteroides/uso terapêutico , Síndrome de Sweet/complicações , Síndrome de Sweet/patologia
18.
Biotech Histochem ; 94(5): 366-373, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30982354

RESUMO

We investigated the effectiveness of crocin for preventing oxidative damage in experimentally produced periodontitis. We used three groups of 10 female Wistar rats divided into: control (C); experimental periodontitis (EP), experimental periodontitis + crocin (Cr-EP). Malondialdehyde (MDA), glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS) and superoxide dismutase (SOD) and catalase (CAT) enzyme activities were measured. We examined histopathology and inflammatory cell infiltration in gingiva and periodontal ligament. MDA and TOS levels, and SOD and CAT activities increased significantly in rats with induced periodontitis compared to the control group, while GSH and TAS levels were decreased significantly compared to the control group. Histopathologic examination revealed inflammatory cell infiltration in gingiva epithelium and subepithelial connective tissue in the EP group. Histological damage was reduced significantly after crocin treatment compared to the EP group. Crocin supplementation may help reduce oxidative damage to periodontal tissues.


Assuntos
Carotenoides/farmacologia , Gengiva/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ligamento Periodontal/efeitos dos fármacos , Periodontite/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Carotenoides/uso terapêutico , Catalase/metabolismo , Feminino , Gengiva/metabolismo , Gengiva/patologia , Glutationa/metabolismo , Malondialdeído/metabolismo , Ligamento Periodontal/metabolismo , Ligamento Periodontal/patologia , Periodontite/metabolismo , Periodontite/patologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
19.
PLoS One ; 14(4): e0214946, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30973902

RESUMO

Smoking is a leading cause of preventable death. The effect of tobacco is even more contundent in people with mental illness and, in general, cigarette smoking addiction is influenced by genetic factors. The opioid system is involved in the mesolimbic reward system, which is of great importance in addictive behaviors, such as smoking and is influenced by genes such as the OPRM1. The aim of this study was to evaluate if selecting a comparison group that include light smokers versus people that never smoked impacts the results of genetic association studies. In addition, to evaluate the genetic association in different groups of smokers by analyzing independent covariates such as mental illness and clinical dental data. All subjects were participants of the Dental Registry and DNA Repository project. Genotyping was carried out using TaqMan chemistry for two markers in OPRM1 (rs553202 and rs7755635). Logistic regression analyses were performed as implemented in PLINK. The established value for alpha was 5%, and the Hardy-Weinberg equilibrium was evaluated by the chi-square test with one degree of freedom for each marker. 1,897 patients were included, which were allocated to eight distinct groups, according to the frequency and quantity of cigarettes smoked and mental illness status. There was no significant association between the two markers in OPRM1 and smoking. When mental illness and dental clinical data (tooth loss, dental caries, and periodontitis) were used as covariates, there were associations between heavy smoking and OPRM1, when non-smokers were used as comparison. We did not have diet or microbiome data to consider for these dental analyses and suggest that these kinds of data should be always incorporated in the future. Significant results were found only when the covariables mental illness and oral clinical data were added to the analysis.


Assuntos
Comportamento Aditivo , Fumar Cigarros , Cárie Dentária , Periodontite , Receptores Opioides mu/genética , Perda de Dente , Adulto , Comportamento Aditivo/genética , Comportamento Aditivo/patologia , Comportamento Aditivo/fisiopatologia , Fumar Cigarros/genética , Fumar Cigarros/patologia , Fumar Cigarros/fisiopatologia , Cárie Dentária/genética , Cárie Dentária/patologia , Cárie Dentária/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Periodontite/genética , Periodontite/patologia , Periodontite/fisiopatologia , Perda de Dente/genética , Perda de Dente/patologia , Perda de Dente/fisiopatologia
20.
J Appl Oral Sci ; 27: e20180205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30994772

RESUMO

Porphyromonas gingivalis is one of the most important Gram-negative anaerobe bacteria involved in the pathogenesis of periodontitis. P. gingivalis has an arsenal of specialized virulence factors that contribute to its pathogenicity. Among them, fimbriae play a role in the initial attachment and organization of biofilms. Different genotypes of fimA have been related to length of fimbriae and pathogenicity of the bacterium. OBJECTIVES: The aim of this study was to identify 5 types of fimA genotype strains in smokers and nonsmokers with periodontitis, before and after periodontal therapy. MATERIAL AND METHODS: Thirty-one patients with periodontitis harboring P. gingivalis were selected: 16 nonsmokers (NS) and 15 smokers (SM). Clinical and microbiological parameters were evaluated at baseline and 3 months after periodontal treatment, namely: plaque index, bleeding on probe, probing depth, gingival recession and clinical attachment level. The frequency of P. gingivalis and fimA genotype strains were determined by polymerase chain reaction. RESULTS: Type I fimA was detected in the majority of SM and NS at baseline, and the frequency did not diminish after 3 months of treatment. The frequency of type II genotype was higher in SM than NS at baseline. After 3 months, statistical reduction was observed only for types II and V fimA genotypes in SM. The highest association was found between types I and II at baseline for NS (37.5%) and SM (53.3%). CONCLUSION: The most prevalent P. gingivalis fimA genotypes detected in periodontal and smoker patients were genotypes I and II. However, the presence of fimA genotype II was higher in SM. Periodontal treatment was effective in controlling periodontal disease and reducing type II and V P. gingivalis fimA.


Assuntos
Proteínas de Fímbrias/isolamento & purificação , Periodontite/microbiologia , Periodontite/terapia , Porphyromonas gingivalis/isolamento & purificação , Fumar/efeitos adversos , Adulto , Idoso , DNA Bacteriano , Feminino , Proteínas de Fímbrias/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Índice Periodontal , Periodontite/patologia , Reação em Cadeia da Polimerase , Porphyromonas gingivalis/genética , Estatísticas não Paramétricas , Fatores de Tempo
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