RESUMO
Periodontal disease (PD) is a polymicrobial chronic inflammatory condition of the supporting tissues around the teeth, leading to the destruction of surrounding connective tissue. During the progression of PD, osteoclasts play a crucial role in the resorption of alveolar bone that eventually leads to the loss of teeth if the PD is left untreated. Therefore, the development of antiresorptive therapies targeting bone-resorbing cells will significantly benefit the treatment of PD. Here, we demonstrate the inhibitory effect of CsinCPI-2, a novel cysteine peptidase inhibitor from the orange tree, on periodontitis-induced inflammation, alveolar bone loss, and osteoclast differentiation. Using the ligature-induced periodontitis model in mice, we show that treatment with CsinCPI-2 (0.8 µg/g of body weight) significantly reduced inflammatory cell infiltrate in the connective tissue and prevented the loss of alveolar bone mass (BV/TV) caused by PD, effects associated with diminished numbers of TRAP-positive multinucleated cells. Furthermore, CsinCPI-2 significantly downregulated the numbers of inflammatory cells expressing CD3, CD45, MAC387, and IL-1ß. In vitro, CsinCPI-2 inhibited RANKL-induced TRAP+ multinucleated osteoclast formation in mouse bone marrow macrophage cultures in a concentration-dependent manner. This effect was not due to cytotoxicity, as demonstrated by the MTT assay. CsinCPI-2 inhibited RANKL-induced mRNA expression of Acp5, Calcr, and Ctsk, as well as the RANKL-induced upregulation of Nfatc1, a crucial transcription factor for osteoclast differentiation. Based on our findings, CsinCPI-2 prevents bone loss induced by PD by controlling the inflammatory process and acting directly on osteoclastogenesis, suggesting an interesting potential for CsinCPI-2 in the strategy for PD treatment.
Assuntos
Perda do Osso Alveolar , Reabsorção Óssea , Cistatinas/farmacologia , Periodontite , Inibidores de Proteases/farmacologia , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/prevenção & controle , Animais , Diferenciação Celular , Camundongos , Osteoclastos , Osteogênese , Periodontite/tratamento farmacológico , Ligante RANKRESUMO
OBJECTIVES: The aim of this study was to evaluate the behavior of rat bone marrow stem cells seeded on a Ti-15Mo alloy surface modified by laser-beam irradiation followed by calcium phosphate deposition. MATERIALS AND METHODS: A total of four groups were evaluated: polished commercially pure titanium (cpTi): Ti-P; laser irradiation + calcium phosphate deposition on cpTi: Ti-LCP; polished Ti-15Mo alloy: Ti15Mo-P; and laser irradiation + calcium phosphate deposition on Ti-15Mo alloy: Ti15Mo-LCP. Before and after laser irradiation and calcium phosphate deposition on the surfaces, physicochemical and morphological analyses were performed: Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy (EDX). The wettability of the samples was evaluated by contact angle measurement. In addition, the behavior of osteoblast-like cells to these surfaces was evaluated for cell morphology, adhesion, proliferation and viability, evaluation of alkaline phosphatase formation and gene expression of osteogenesis markers. RESULTS: Surfaces wet-abrade with grit paper (P) showed oriented groves, while the laser irradiation and calcium phosphate deposition (LCP) produced porosity on both cpTi and Ti15Mo alloy groups with deposits of hydroxyapatite (HA) crystals (SEM). EDX showed no contamination after surface modification in both metal samples. A complete wetting was observed for both LCP groups, whereas P surfaces exhibited high degree of hydrophobicity. There was a statistical difference in the intragroup comparison of proliferation and viability (p < 0.05). The ALP activity showed higher values in the Ti15Mo alloy at 10 days of culture. The gene expression of bone related molecules did not present significant differences at 7 and 14 days among different metals and surface treatments. CONCLUSION: Ti15-Mo seems to be an alternative alloy to cpTi for dental implants. Surface treatment by laser irradiation followed by phosphate deposition seems to positively interact with bone cells. CLINICAL RELEVANCE: Ti-15Mo alloy surface modified by laser-beam irradiation followed by calcium phosphate deposition may improve and accelerate the osseointegration process of dental implants.
Assuntos
Células da Medula Óssea/citologia , Fosfatos de Cálcio/química , Implantes Dentários , Perfilação da Expressão Gênica , Osteoblastos/metabolismo , Células-Tronco/citologia , Ligas , Animais , Adesão Celular , Proliferação de Células , Sobrevivência Celular , Técnicas In Vitro , Lasers , Metais/química , Microscopia Eletrônica de Varredura , Osseointegração , Osteogênese , Desenho de Prótese , Ratos , Propriedades de Superfície , Titânio/químicaRESUMO
INTRODUCTION: Periodontitis is characterized by inflammatory mediators beyond T lymphocyte function and phenotype (Th1/Th2/Th17). The clinical diversity in periodontitis makes it difficult to characterize the immune response in patients. This study evaluated the profile of the adaptive immune response in the periodontal disease model. METHODS: 72 rats (Wistar) were divided into a control group (CTL/day 0) and periodontitis (PD15/15 days and PD60/60 days). In the PD15 and PD60 groups, periodontal disease was induced by ligature with a silk thread placed in the cervical region of the upper first molar. After euthanasia, the periodontal tissue was analyzed by flow cytometry (CD4, CD8, CD25, CD44), semi-quantitative RT-PCR (T-bet, GATA-3, RORγt), semi-quantitative RT-PCR and ELISA IFN-γ, TNF-α, IFN-γ, IL-4, IL-6, IL-10, IL-17) and by Western blotting (Caspase-9, PCNA). RESULTS: The number of CD4+CD25+, CD4+CD44+, CD8+CD25+ and CD8+CD44+ cells and expression levels of T-bet and GATA-3 are increased in the PD60 group compared to PD15 and CTL. The RORγ-t gene transcript increased in the PD15 group in relation to PD60 and CTL. The cytokines IFN-γ, TNF-α and IL-17 increased in the PD60 group in relation to PD15. The expression of Caspase-9 was higher in the PD60 group than in PD15. CONCLUSIONS: The results suggest that the evolution of gingivitis to periodontitis is related to the accumulation of activated Th1 cells (IFN-γ and TNF-α) associated with the presence of increased IL-17. Studies with inhibitors of these cytokines in periodontal disease may lead to therapy directed at blocking the inflammatory process in this pathology, interrupting bone loss.
Assuntos
Caspase 9/imunologia , Interleucina-17/imunologia , Periodontite/imunologia , Células Th1/imunologia , Animais , Western Blotting , Modelos Animais de Doenças , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Masculino , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND AND OBJECTIVE: Although chronic periodontitis (CP) is a multifactorial condition, few studies have investigated the potential association of gene variants with the outcome of periodontal therapy. In a previous study, we reported that variants in the interleukin-8 (IL8) gene were associated with CP in a Brazilian population. The aim of this nonrandomized study was to investigate whether genetic susceptibility to CP, conferred by the presence of the IL8 ATC/TTC haplotype, influences the clinical outcomes of nonsurgical periodontal therapy and the IL-8 protein levels in the gingival crevicular fluid. MATERIAL AND METHODS: Forty-one individuals were grouped according to the presence (susceptible to CP; n = 21) or absence (not susceptible to CP; n = 20) of the IL8 ATC/TTC haplotype. These individuals received nonsurgical periodontal therapy from one periodontist, who was blinded to the genetic status of each patient, and follow up continued for 45 d. The clinical parameters and gingival crevicular fluid samples were collected at baseline and on day 45. The IL-8 levels were determined by an ELISA. The data were subjected to the Mann-Whitney U-test, Wilcoxon and Spearman tests and to multiple logistic-regression analysis. RESULTS: No significant differences between patients with or without the IL8 ATC/TTC haplotype were found for the outcome of nonsurgical periodontal therapy and IL-8 levels. The multiple logistic-regression analysis did not show a statistically significant association between the IL8 haplotype and the variables studied. CONCLUSION: In this longitudinal clinical study, we observed that neither the outcome of nonsurgical periodontal therapy nor the IL-8 levels were influenced by the IL8 ATC/TTC CP-susceptibility haplotype. Additional studies of CP patients from other ethnic populations are necessary to confirm these results.
Assuntos
Adenina , Periodontite Crônica/terapia , Citosina , Haplótipos/genética , Interleucina-8/genética , Timina , Adulto , Periodontite Crônica/genética , Índice de Placa Dentária , Feminino , Seguimentos , Predisposição Genética para Doença/genética , Líquido do Sulco Gengival/química , Líquido do Sulco Gengival/imunologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal/terapia , Índice Periodontal , Bolsa Periodontal/terapia , Método Simples-Cego , Resultado do TratamentoRESUMO
Periodontitis is an inflammatory disease that results from an interaction between dental biofilm agents and the host immune-inflammatory response. Periodontopathogenic organisms, such as Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, as well as the host's susceptibility, represented by the host's genetic makeup, are the key factors that influence this complex disease. Recently, we identified haplotypes in the IL4 gene that were associated with chronic periodontitis (CP). This study aimed to evaluate whether subjects with different IL4 haplotypes (TCI/CCI and TTD/CTI) would be differentially colonized by periodontopathogens and whether they would respond differently to non-surgical periodontal therapy. Thirty-nine patients carrying the IL4 haplotype of genetic susceptibility to CP (IL4+) or protection against CP (IL4-) were evaluated. Those groups were further subdivided into individuals with CP (CP IL4+ or CP IL4-) and those that were periodontally healthy (H) (H IL4+ or H IL4-). CP patients were submitted to non-surgical periodontal therapy. Clinical and microbiological analyses were performed considering the data at baseline and 45 and 90 days after periodontal therapy. Periodontopathogens levels were evaluated by absolute quantitative polymerase chain reaction (qPCR). The baseline data revealed that the total levels of periodontopathogens were higher in the CP IL4+ than in the CP IL4- groups. Clinical analyses revealed that the periodontal therapy was equally effective, independent of the subject's IL4 genetic load. The TCI/CCI IL4 haplotype, previously associated with genetic susceptibility to CP, was also associated with increased levels of periodontopathogenic bacteria, but this genetic background did not influence the response to non-surgical periodontal treatment.
Assuntos
Periodontite Crônica/microbiologia , Interleucina-4/genética , Adulto , Carga Bacteriana , Bacteroides/isolamento & purificação , Distribuição de Qui-Quadrado , Periodontite Crônica/genética , Periodontite Crônica/imunologia , Periodontite Crônica/terapia , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Interleucina-4/imunologia , Masculino , Pessoa de Meia-Idade , Porphyromonas gingivalis/isolamento & purificação , Resultado do Tratamento , Treponema denticola/isolamento & purificaçãoRESUMO
Chronic periodontitis (CP) is considered to be a multifactorial disease influenced by microbial and genetic factors. The aim of the present study was to investigate whether the genetic susceptibility to CP in individuals with the IL8 ATC/TTC haplotype is associated with subgingival levels of periodontopathogens. Sixty-five individuals, grouped according to the presence (n = 28) or absence (n = 37) of the IL8 haplotype, were evaluated. After clinical periodontal evaluation, each group was subdivided according to the presence (CP) or absence (H) of periodontitis. Four subgingival samples were obtained from CP and two samples per subject from H patients. The levels and proportions of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola were analyzed using quantitative real-time polymerase chain reaction (q-PCR). No differences were found in the proportion of periodontopathogenic bacteria between groups with the presence or absence of the IL8 haplotype. However, in the CP groups, the levels of periodontopathogens were significantly higher in the individuals without the IL8 haplotype than in the individuals with the IL8 haplotype. These results suggest that periodontal destruction may occur in patients who are considered to be genetically susceptible to CP with a lower microbial challenge because of the presence of the IL8 ATC/TTC haplotype than in patients without this haplotype.
Assuntos
Carga Bacteriana , Bacteroidetes/isolamento & purificação , Periodontite Crônica/imunologia , Predisposição Genética para Doença , Interleucina-8/genética , Porphyromonas gingivalis/isolamento & purificação , Treponema denticola/isolamento & purificação , Adulto , Bacteroidetes/imunologia , Periodontite Crônica/microbiologia , Feminino , Haplótipos , Humanos , Interleucina-8/imunologia , Masculino , Pessoa de Meia-Idade , Porphyromonas gingivalis/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Treponema denticola/imunologiaRESUMO
Preterm birth is a major problem in public health in developed and developing countries and the search for risk factors of this event is important. The aim of this study was to review the effect of periodontal treatment on the incidence of preterm delivery. A wide research was executed considering an evaluation period between November of 1998 and October of 2009 at MEDLINE/PUBMED databases. The selection strategy consisted of the search for the following key-words: "periodontal therapy" or "periodontal disease" and "pregnancy outcome" or "preterm birth". The search was limited for articles written in English. The randomized clinical trials that evaluated the effect of the non-surgical periodontal treatment on the incidence of Preterm Low Birth Weight (PLBW) were selected. In a total of 7 papers selected, the incidence of PLBW was lower in groups of women who were submitted to periodontal treatment. Reductions of Preterm Birth (PTB) ranged from 0.8% to 28.01%, while reduction of Low Birth Weight (LBW) ranged from 0.44% to 33%. In studies that analyzed these two variables together, there was variation between 4.57% to 71.5% in rates reduction. Due to heterogeneity of the data, the meta-analysis was not applied. The majority of the studies concluded that non-surgical periodontal treatment in pregnant women reduces incidence of preterm babies with low weight.
Assuntos
Trabalho de Parto Prematuro/epidemiologia , Doenças Periodontais/terapia , Feminino , Humanos , Incidência , Trabalho de Parto Prematuro/etiologia , Doenças Periodontais/complicações , Gravidez , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: This review of the literature intends to evaluate the effect of brushes with high frequency motion when compared with manual toothbrushes regarding the indices of plaque and gingival bleeding. METHODS: Patients presenting gingivitis and/or chronic periodontitis were evaluated in addition to patients having osseointegrated implants and fixed orthodontic appliances. Pertinent literature was reviewed to select articles according to previously defined inclusion criteria. RESULTS: In the assessed studies results showed significant decreases in plaque and gingival indices by utilization of both types of brushes. However, in the selected studies where sonic brushes were tested in orthodontic and dental implant patients there was a more significant decrease in the indices. Furthermore, there was no indication of gingival recession attributed to product use. CONCLUSION: Future studies with a more homogeneous methodology and better experiment designs will be needed.
Assuntos
Placa Dentária/prevenção & controle , Gengivite/prevenção & controle , Escovação Dentária/instrumentação , Dispositivos para o Cuidado Bucal Domiciliar , Implantes Dentários , Humanos , Aparelhos Ortodônticos , Periodontite/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia por UltrassomRESUMO
BACKGROUND: The poor predictability of periodontal regenerative treatment of Class III furcation defects stimulates the study of alternatives to improve its results, such as the use of polypeptide growth factors. The objective of this study was to evaluate, both histologically and histometrically, the effects of topical application of basic fibroblast growth factor (b-FGF) associated with guided tissue regeneration (GTR) in the treatment of Class III defects surgically induced in dogs. METHODS: All second and fourth premolars of 5 mongrel dogs were used and randomly assigned to one of three treatment groups: group 1 (control), treated with scaling and root planing, tetracycline hydrochloride (125 mg/ml) conditioning, and GTR with a collagen membrane; group 2, same treatment as group 1 plus 0.5 mg of b-FGF; group 3, same treatment as group 1 plus 1.0 mg of b-FGF. After a 90-day healing period, routine histologic processing and staining with hematoxylin and eosin and Masson trichrome were performed. RESULTS: The descriptive analysis indicated better regenerative results in both groups treated with b-FGF while the histometric data, analyzed by means of analysis of variance (ANOVA), showed greater filling of the defects in group 2 in comparison to the defects in groups 3 and 1, respectively, which was represented by a smaller area of plaque-occupied space (P = 0.004) as well as a greater amount of newly formed cementum (P = 0.002). CONCLUSIONS: These results indicate that b-FGF, especially in smaller doses, may enhance the regenerative results in Class III furcation lesions, leading to greater filling of these defects with both mineralized and non-mineralized tissues.