RESUMO
Functional neuronal connectivity requires proper neuronal morphogenesis and its dysregulation causes neurodevelopmental diseases. Transforming growth factor-ß (TGF-ß) family cytokines play pivotal roles in development, but little is known about their contribution to morphological development of neurons. Here we show that the Smad-dependent canonical signaling of TGF-ß family cytokines negatively regulates neuronal morphogenesis during brain development. Mechanistically, activated Smads form a complex with transcriptional repressor TG-interacting factor (TGIF), and downregulate the expression of a neuronal polarity regulator, collapsin response mediator protein 2. We also demonstrate that TGF-ß family signaling inhibits neurite elongation of human induced pluripotent stem cell-derived neurons. Furthermore, the expression of TGF-ß receptor 1, Smad4, or TGIF, which have mutations found in patients with neurodevelopmental disorders, disrupted neuronal morphogenesis in both mouse (male and female) and human (female) neurons. Together, these findings suggest that the regulation of neuronal morphogenesis by an evolutionarily conserved function of TGF-ß signaling is involved in the pathogenesis of neurodevelopmental diseases.SIGNIFICANCE STATEMENT Canonical transforming growth factor-ß (TGF-ß) signaling plays a crucial role in multiple organ development, including brain, and mutations in components of the signaling pathway associated with several human developmental disorders. In this study, we found that Smads/TG-interacting factor-dependent canonical TGF-ß signaling regulates neuronal morphogenesis through the suppression of collapsin response mediator protein-2 (CRMP2) expression during brain development, and that function of this signaling is evolutionarily conserved in the mammalian brain. Mutations in canonical TGF-ß signaling factors identified in patients with neurodevelopmental disorders disrupt the morphological development of neurons. Thus, our results suggest that proper control of TGF-ß/Smads/CRMP2 signaling pathways is critical for the precise execution of neuronal morphogenesis, whose impairment eventually results in neurodevelopmental disorders.
Assuntos
Proteínas de Homeodomínio/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Morfogênese/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Neurônios/fisiologia , Proteínas Repressoras/fisiologia , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta/fisiologia , Animais , Axônios/efeitos dos fármacos , Células Cultivadas , Dendritos/efeitos dos fármacos , Feminino , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Proteínas de Homeodomínio/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Camundongos , Mutação/genética , Proteínas do Tecido Nervoso/genética , Doenças do Sistema Nervoso/genética , Células-Tronco Neurais , Gravidez , Proteínas Repressoras/genética , Proteína Smad4/genética , Proteína Smad4/fisiologiaRESUMO
Recent studies suggest that the commensal microbiota affects not only host energy metabolism and development of immunity but also bone remodeling by positive regulation of osteoclast activity. However, the mechanism of regulation of bone cells by the commensal microbiota has not been elucidated. In this study, 8-week-old specific pathogen-free (SPF) and germ-free (GF) mice were compared in terms of alveolar bones and primary osteoblasts isolated from calvarias. Micro-CT analysis showed that SPF mice had larger body size associated with lower bone mineral density and bone volume fraction in alveolar bones compared with GF mice. Greater numbers of osteoclasts in alveolar bone and higher serum levels of tartrate-resistant acid phosphatase 5b were observed in SPF mice. Tissue extracts from SPF alveolar bone showed higher levels of cathepsin K, indicating higher osteoclast activity. SPF alveolar extracts also showed elevated levels of γ-carboxylated glutamic acidâ»osteocalcin as a marker of mature osteoblasts compared with GF mice. Polymerase chain reaction (PCR) array analysis of RNA directly isolated from alveolar bone showed that in SPF mice, expression of mRNA of osteocalcin, which also acts as an inhibitor of bone mineralization, was strongly enhanced compared with GF mice. Cultured calvarial osteoblasts from SPF mice showed reduced mineralization but significantly enhanced expression of mRNAs of osteocalcin, alkaline phosphatase, insulin-like growth factor-I/II, and decreased ratio of osteoprotegerin/receptor activator of nuclear factor-kappa B ligand compared with GF mice. Furthermore, PCR array analyses of transcription factors in cultured calvarial osteoblasts showed strongly upregulated expression of Forkhead box g1. In contrast, Gata-binding protein 3 was strongly downregulated in SPF osteoblasts. These results suggest that the commensal microbiota prevents excessive mineralization possibly by stimulating osteocalcin expression in osteoblasts, and enhances both osteoblast and osteoclast activity by regulating specific transcription factors.
Assuntos
Remodelação Óssea/genética , Microbioma Gastrointestinal/fisiologia , Vida Livre de Germes , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese/genética , Simbiose/fisiologia , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Biomarcadores/metabolismo , Catepsina K/genética , Catepsina K/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Regulação da Expressão Gênica , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Camundongos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Osteoblastos/citologia , Osteoblastos/microbiologia , Osteocalcina/genética , Osteocalcina/metabolismo , Osteoclastos/citologia , Osteoclastos/microbiologia , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismoRESUMO
Proper dendritic elaboration of neurons is critical for the formation of functional circuits during brain development. Defects in dendrite morphogenesis are associated with neuropsychiatric disorders, and microRNAs are emerging as regulators of aspects of neuronal maturation such as axonal and dendritic growth, spine formation, and synaptogenesis. Here, we show that miR-214 plays a pivotal role in the regulation of dendritic development. Overexpression of miR-214 increased dendrite size and complexity, whereas blocking of endogenous miR-214-3p, a mature form of miR-214, inhibited dendritic morphogenesis. We also found that miR-214-3p targets quaking (Qki), which is implicated in psychiatric diseases such as schizophrenia, through conserved target sites located in the 3'-untranslated region of Qki mRNA, thereby down-regulating Qki protein levels. Overexpression and knockdown of Qki impaired and enhanced dendritic formation, respectively. Moreover, overexpression of Qki abolished the dendritic growth induced by miR-214 overexpression. Taken together, our findings reveal a crucial role for the miR-214-Qki pathway in the regulation of neuronal dendritic development.
Assuntos
Dendritos/metabolismo , Regulação para Baixo , MicroRNAs/metabolismo , Proteínas de Ligação a RNA/biossíntese , Sinapses/metabolismo , Animais , Axônios/metabolismo , Dendritos/genética , Camundongos , MicroRNAs/genética , Proteínas de Ligação a RNA/genética , Esquizofrenia/genética , Esquizofrenia/metabolismo , Sinapses/genéticaRESUMO
BACKGROUND: Development of periodontal disease (PD) may be affected by socioeconomic status. This study examined the relationship between occupational status and PD in a 5-year prospective cohort of Japanese workers. METHODS: In total, 19,633 participants had initial examinations at the Aichi Health Promotion Foundation, of whom 8210 participants aged 20 years or older did not have PD. Follow-up examinations were conducted for 3757 participants, accounting for 45.8% of baseline participants. Ultimately, 3390 participants were analyzed according to the criterion of job classification at baseline, which was based on the International Standard Classification of Occupations, 1987. Oral examinations were performed using the Community Periodontal Index (CPI). The CPI scores were coded as follows: healthy (score of 0); bleeding after probing (1); dental calculus (2); shallow pockets (3); and deep pockets (4). Participants with one or more sextants with a score >2 were diagnosed with PD. Poisson regression analysis was performed to adjust for age and other potential confounders. RESULTS: Overall, 31.6% of men and 23.8% of women had developed PD (CPI scores of 3 or 4). The adjusted relative risk (RR) for PD (CPI scores of 3 or 4) in men was not significant. On the other hand, the adjusted RRs for PD (CPI score of 4) in men were 2.52-, 2.39-, and 2.74-fold higher for skilled workers, sales persons, and drivers, respectively, than for professionals. In contrast, we found no gradient in women. CONCLUSIONS: We found a gradient related to the risk of developing PD according to occupational status among men in a Japanese worker population.
Assuntos
Emprego/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Doenças Periodontais/epidemiologia , Adulto , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Distribuição por Sexo , Adulto JovemRESUMO
The aim of this study was to investigate whether a Keap1-dependent oxidative stress detector-luciferase (OKD-LUC) mouse model would be useful for the visualization of oxidative stress induced by experimental periodontitis. A ligature was placed around the mandibular first molars for seven days to induce periodontitis. Luciferase activity was measured with an intraperitoneal injection of d-luciferin on days 0, 1, and 7. The luciferase activity in the periodontitis group was significantly greater than that in the control group at seven days. The expressions of heme oxygenase-1 (HO-1) and malondialdehyde in periodontal tissue were significantly higher in the periodontitis group than in the control group. Immunofluorescent analysis confirmed that the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) occurred more frequently in the periodontitis group than in the control group. This study found that under oxidative stress induced by experimental periodontitis, the Nrf2/antioxidant defense pathway was activated and could be visualized from the luciferase activity in the OKD-LUC model. Thus, the OKD-LUC mouse model may be useful for exploring the mechanism underlying the relationship between the Nrf2/antioxidant defense pathway and periodontitis by enabling the visualization of oxidative stress over time.
Assuntos
Heme Oxigenase-1/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Luciferases/metabolismo , Imagem Óptica , Estresse Oxidativo , Periodontite/diagnóstico por imagem , Periodontite/metabolismo , Animais , Modelos Animais de Doenças , Luminescência , Malondialdeído/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Imagem Óptica/métodos , Periodontite/patologiaRESUMO
AIM: The purpose of this longitudinal study was to investigate whether self-efficacy scale for self-care (SESS) was related to changes in oral health behaviours and progression of periodontal disease in Japanese university students. MATERIAL AND METHODS: Students (n = 533) who were interested in receiving oral health examinations before entering the university and before graduation were included in the analysis. Self-efficacy was assessed using SESS, which uses three subscales: self-efficacy for brushing of the teeth (SE-BR), for dentist consultations (SE-DC) and for dietary habits. The informations about oral health behaviours were also collected. For all participants, oral hygiene instructions was performed at baseline. After 3 years, the oral health behaviours and the periodontal condition were re-assessed. RESULTS: The progression of periodontal disease was related to low baseline SE-BR. Logistic regression analysis showed that progression of periodontal disease risk during a 3-year period was associated with low baseline SE-BR (OR: 1.516; 95% CI: 1.010-2.275; p < 0.05). The increase in the score of SE-DC was related to the increase in regular dental checkups (p < 0.05). CONCLUSION: Low SESS was associated with progression of periodontal disease and improvement of oral health behaviours in university students who received oral hygiene instructions at baseline.
Assuntos
Doenças Periodontais , Humanos , Estudos Longitudinais , Saúde Bucal , Estudos Prospectivos , AutoeficáciaRESUMO
OBJECTIVE: Some studies have shown a relationship between psychological symptoms and oral health behaviors. However, it is unknown whether gender differences affect the relationship between psychological symptoms and oral health behaviors. In addition, gender differences in the relationship between dental anxiety and dental visits for treatment or regular check-up are unclear. The objective of the present study was to explain the relationships among gender differences, psychological symptoms, oral health behaviors, dental anxiety and 'expectation of dental visit', evaluated as 'dental visits when treatments are recommended' in university students. MATERIALS AND METHODS: A total of 607 students (311 males, 296 females) aged 18-38 years old were examined. The information was collected via questionnaire regarding gender, psychological symptoms and oral health behaviors. Psychological symptoms were assessed using the Hopkins Symptom Checklist. Structural equation modeling was used to test pathways from these factors to 'expectation of dental visit'. Multiple-group modeling was also conducted to test for gender differences. RESULTS: Psychological symptoms were related to low expectation of dental visit in females, but there was no such relationship in males. Oral health behaviors were related to expectation of dental visit in both genders. CONCLUSIONS: Psychological symptoms were directly related to expectation of dental visit in females and oral health behaviors were related to expectation of dental visit in both genders. To promote dental visits after dental check-ups at school, it might be necessary to improve oral health behaviors in both genders and to evaluate psychological symptoms, especially in females.
Assuntos
Assistência Odontológica/psicologia , Comportamentos Relacionados com a Saúde , Saúde Bucal , Estudantes/psicologia , Adulto , Ansiedade/psicologia , Atitude Frente a Saúde , Ansiedade ao Tratamento Odontológico/psicologia , Dispositivos para o Cuidado Bucal Domiciliar , Depressão/psicologia , Feminino , Humanos , Masculino , Modelos Psicológicos , Fatores Sexuais , Inquéritos e Questionários , Escovação Dentária/psicologia , Universidades , Adulto JovemRESUMO
AIM: The purpose of this prospective cohort study was to investigate whether body mass index (BMI) and oral health behaviour are related to changes in periodontal status in Japanese university students. MATERIALS AND METHODS: Students (n = 224) who were interested in receiving oral health examinations before entering university and before graduation were included in the analysis. Subjects were investigated regarding the correlations of oral health behaviours and increases in BMI with the percentage of bleeding on probing (%BOP) and Community Periodontal Index (CPI) scores as indicators of changes in periodontal status. RESULTS: The risk of increased %BOP was associated with the non-use of dental floss (adjusted odds ratio [OR]: 3.11; 95% confidence interval [CI]: 1.31-7.37; p < 0.05), whereas the risk of increased CPI score was associated with increases in BMI (OR: 1.95; 95% CI: 1.05-3.65; p < 0.05) and simplified oral hygiene index score (OR: 2.28; 95% CI: 1.23-4.22; p < 0.01). CONCLUSION: Increases in BMI were associated with worsening of periodontal status, defined as increased CPI score in Japanese university students, whereas lack of inter-dental cleaning was associated with exacerbated gingival bleeding.
Assuntos
Índice de Massa Corporal , Índice Periodontal , Adolescente , Adulto , Composição Corporal , Estudos de Coortes , Assistência Odontológica , Dispositivos para o Cuidado Bucal Domiciliar , Feminino , Seguimentos , Comportamentos Relacionados com a Saúde , Nível de Saúde , Humanos , Masculino , Obesidade/classificação , Saúde Bucal , Índice de Higiene Oral , Sobrepeso/classificação , Estudos Prospectivos , Fumar , Magreza/classificação , Escovação Dentária , Adulto JovemRESUMO
BACKGROUND: Psychosocial stress is one of the risk factors for atherosclerosis. As occlusal disharmony induces psychological stress, we hypothesized that psychological stress by occlusal disharmony accelerates atherosclerosis. The aim of this study was to investigate the effects of occlusal disharmony on the initiation of atherosclerosis in apolipoprotein E (apoE) knockout rats. METHODS: Fourteen male apoE-knockout rats (age; 8 weeks) (Sprague-Dawley strain background) were divided into two groups of seven rats: the occlusal disharmony group and the no treatment (control) group. In the occlusal disharmony group, the maxillary molar cusps were cut off for the 8-week experimental period. RESULTS: In the occlusal disharmony group, the percentages of the area of total aortic lumen occupied by plaques and lipid were significantly higher than those in the control group (p < 0.05, t-test). The occlusal disharmony group also showed significantly higher serum levels of very low-density lipoprotein-cholesterol (VLDL) and low-density lipoprotein-cholesterol (LDL), plasma levels of corticosterone (1.9, 1.3 and 1.3 times, respectively), higher aortic protein expression levels of vascular cell adhesion molecule-1 (VCAM1) and intercellular adhesion molecule-1 (ICAM1) (1.5 and 1.4 times, respectively), and higher aortic gene expression of levels of VCAM1 and Toll-like receptor 4 (TLR4) (1.9 and 4.3 times, respectively), as compared to the control group (p < 0.05). However, there were no significant differences in serum levels of oxidized LDL, reactive oxygen metabolites and C-reactive protein between the two groups. CONCLUSION: In apoE knockout rats, occlusal disharmony may induce VCAM1, ICAM1 and TLR4 expression and accelerate the initiation of atherosclerosis.
Assuntos
Apolipoproteínas E/genética , Aterosclerose/psicologia , Estresse Psicológico/complicações , Animais , Aorta Torácica/imunologia , Aorta Torácica/patologia , Aterosclerose/sangue , Aterosclerose/imunologia , Proteína C-Reativa/metabolismo , Técnicas de Inativação de Genes , Molécula 1 de Adesão Intercelular/metabolismo , Macrófagos/imunologia , Masculino , Placa Aterosclerótica/imunologia , Placa Aterosclerótica/metabolismo , Ratos Sprague-Dawley , Ratos Transgênicos , Espécies Reativas de Oxigênio/sangue , Estresse Psicológico/sangue , Estresse Psicológico/imunologia , Receptor 4 Toll-Like/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
OBJECTIVE: Buccal mucosa ridging (BMR) is known as a clinical sign of clenching, which is one of the major manifestations of bruxism. However, there are few reports about the formation of BMR and no data regarding the association between BMR and factors such as malocclusion. The purpose of the current study was to investigate the relationship between BMR and factors such as the number of teeth present, gender, body mass index (BMI), occlusion and clenching habit in university students. MATERIALS AND METHODS: A total of 2101 students (1164 males, 937 females), aged 18-29 years old, were included in the study. BMR and the number of teeth present were recorded and malocclusion was defined using a modified version of the Index of Orthodontic Treatment Need. Additional information regarding gender, clenching habit and BMI was collected via a questionnaire. RESULTS: Forty-six per cent of the subjects had BMR and the prevalence of BMR in females was significantly higher than that of males (chi square test, p < 0.001). According to logistic regression analysis, the probability of BMR was significantly associated with female gender (OR = 1.501, 95% CI = 1.259-1.790, p < 0.001), crowding (OR = 2.102, 95% CI = 1.706-2.590, p < 0.001) and overjet (OR = 0.585, 95% CI = 0.418-0.818, p = 0.002). On the other hand, BMR was not associated with awareness of clenching habit and BMI. CONCLUSIONS: Gender, crowding and overjet were related to the formation of BMR in university students. When evaluating BMR as a clinical sign of clenching, one might have to take factors such as gender and crowding into consideration.
Assuntos
Mucosa Bucal/anatomia & histologia , Estudantes , Adolescente , Adulto , Bruxismo/patologia , Feminino , Humanos , Masculino , Mucosa Bucal/patologia , Universidades , Adulto JovemRESUMO
We aimed to investigate the relationship between the risk of oral frailty and awareness of oral frailty among Japanese adults in an adult dental health field study conducted in Kanagawa Prefecture. Questionnaire data from a total of 5051 individuals (1907 males, 3144 females; mean age; 59.9 years) were used. The risk of oral frailty was assessed using the Oral Frailty Index-8. Of the participants, 1418 (28.1%) had a high risk of oral frailty and 1495 (29.6%) had knowledge of oral frailty. Logistic regression analysis indicated that the risk of oral frailty was significantly associated with awareness of oral frailty. We further found that awareness of oral frailty was significantly related to gender (female), age (20-39 compared to 70-79, ≥ 80), residential areas (Yokohama compared to Kawasaki, Sagamihara), exercise habits (yes), eating a balanced diet (yes), consciousness of oral health (yes), risk of oral frailty (low) and outpatient category (hospital visit). For groups with low levels of awareness obtained from the results of this study, it is necessary to consider the means of accessibility and increase awareness further.
Assuntos
Fragilidade , Masculino , Adulto , Idoso , Humanos , Feminino , Fragilidade/epidemiologia , Vida Independente , Idoso Fragilizado , Estudos Transversais , Inquéritos e Questionários , Avaliação GeriátricaRESUMO
Background: Salivary lactate dehydrogenase (LD) levels are a feasible and useful parameter for screening periodontal diseases. The periodontal inflamed surface area (PISA) is useful to clinically assess periodontal diseases. However, PISA is difficult to calculate and PISA-compatible screening kits are required. We aimed to investigate the association between salivary LD levels, using a test kit, and PISA and PISA-Japanese and determine the feasibility and reliability of the salivary LD test kit for evaluation of periodontal status. Methods: This study included 110 patients (66.4% female, median and 25-75 percentiles of age were 66.5 and 53.0-75.0 years, respectively) who visited the Dental University Clinic in Japan. Resting saliva samples were collected from each participant and LD levels were evaluated in real time using a kit featuring an integer scale ranging from 1 to 10. PISA and PISA-Japanese were calculated using periodontal parameters. Results: The median salivary LD level was 4.0. The medians of PISA and PISA-Japanese were 46.9 and 61.0, respectively. Salivary LD levels were positively correlated with the bleeding on probing rate (r = 0.626, p < 0.001), PISA (r = 0.560, p < 0.001), and PISA-Japanese (r = 0.581, p < 0.001). Conclusions: Our results suggest that salivary LD levels assessed using the salivary LD kit showed a significantly positive correlation with PISA and PISA-Japanese. In addition, we developed the PISA estimation formula using salivary LD levels measured with a test kit, sex, and age.
RESUMO
How group 3 innate lymphoid cells (ILC3s) regulate mucosal protection in the presence of T cells remains poorly understood. Here, we examined ILC3 function in intestinal immunity using ILC3-deficient mice that maintain endogenous T cells, T helper 17 (TH17) cells, and secondary lymphoid organs. ILC3s were dispensable for generation of TH17 and TH22 cell responses to commensal and pathogenic bacteria, and absence of ILC3s did not affect IL-22 production by CD4 T cells before or during infection. However, despite the presence of IL-22-producing T cells, ILC3s and ILC3-derived IL-22 were required for maintaining homeostatic functions of the intestinal epithelium. T cell-sufficient, ILC3-deficient mice were capable of pathogen clearance and survived infection with a low dose of Citrobacter rodentium. However, ILC3s promoted pathogen tolerance at early time points of infection by activating tissue-protective immune pathways. Consequently, ILC3s were indispensable for survival after high-dose infection. Our results demonstrate a context-dependent role for ILC3s in immune-sufficient animals and provide a blueprint for uncoupling of ILC3 and TH17 cell functions.
Assuntos
Citrobacter rodentium , Infecções por Enterobacteriaceae , Imunidade Inata , Mucosa Intestinal , Linfócitos , Camundongos Endogâmicos C57BL , Animais , Imunidade Inata/imunologia , Camundongos , Linfócitos/imunologia , Citrobacter rodentium/imunologia , Infecções por Enterobacteriaceae/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Camundongos Knockout , Interleucina 22 , Imunidade nas Mucosas/imunologia , Células Th17/imunologiaRESUMO
AIM: Trehalose, which is a disaccharide formed by a 1,1 linkage of two glucose molecules, was suggested to have a suppressive effect on bone resorption. In this study, we examined the effects of topical application of trehalose on osteoclast differentiation in a rat periodontitis model. MATERIAL AND METHODS: Rats were divided into four groups. One group received no treatment. In the other groups, experimental periodontitis was induced by ligature placement. These rats with experimental periodontitis received topical application of pure water (vehicle group), 30 mg/ml trehalose solution (30 mg/ml trehalose group) or 60 mg/ml trehalose solution (60 mg/ml trehalose group) to the gingival sulcus respectively. RESULTS: The vehicle group showed higher numbers of polymorphonuclear leucocytes, receptor activator of nuclear factor kappa B ligand (RANKL)-positive cells and osteoclasts compared with the no treatment group respectively. Trehalose-applied groups exhibited lower numbers of these cells compared with the vehicle group. Gene expressions of tumour necrosis factor-α, RANKL and toll-like receptor 4 were suppressed by trehalose. In addition, protein expressions of RANKL inducing pathway were less activated by trehalose. CONCLUSION: Topical application of trehalose could suppress osteoclast differentiation by inactivation of RANKL inducing pathway in the rat periodontitis model.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Periodontite/metabolismo , Periodontite/patologia , Trealose/farmacologia , Animais , Western Blotting , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/biossíntese , Expressão Gênica , Masculino , Ligante RANK/antagonistas & inibidores , Ligante RANK/biossíntese , Ligante RANK/genética , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/biossíntese , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genéticaRESUMO
AIM: Lipopolysaccharide is a bacterial virulence factor implicated in chronic periodontitis, which may penetrate the junctional epithelial barrier and basement membrane to insult underlying stroma. We sought to identify lipopolysaccharide-induced global gene expression changes responsible for signalling between stroma and epithelium during disease onset. MATERIALS AND METHODS: Using a rat lipopolysaccharide periodontitis model, junctional epithelium and underlying stromal tissue were separately collected from healthy and diseased animals by laser-capture microdissection and subject to gene expression microarray analysis. Key gene products identified were validated in gingival epithelial and fibroblast cell cultures. RESULTS: Global gene expression patterns distinguishing health versus disease were found in and between both tissue types. In stroma, the most significantly altered gene ontology function group (Z ≥ 4.00) was cytokines, containing most significantly (±2-fold; p < 0.05) upregulated genes amphiregulin, IL1-ß and Fas ligand, all positive, diffusible modulators of the epithelial growth factor receptor pathway. In epithelium, the most significant changes were in downregulated FOS-related antigen-1 gene, somatostatin receptor-2 gene and mucin-4 gene, all negative modulators of the epithelial growth factor receptor pathway. CONCLUSION: These results establish a periodontitis model for studying gene product interactions and suggests that the onset of junctional epithelial disease hyperproliferation involves a concerted stromal-epithelial signalling axis.
Assuntos
Periodontite Crônica/metabolismo , Periodontite Crônica/microbiologia , Receptores ErbB/fisiologia , Porphyromonas gingivalis/fisiologia , Transdução de Sinais/efeitos dos fármacos , Anfirregulina , Animais , Células Cultivadas , Família de Proteínas EGF , Inserção Epitelial/citologia , Inserção Epitelial/metabolismo , Células Epiteliais , Proteína Ligante Fas/genética , Fibroblastos , Perfilação da Expressão Gênica , Glicoproteínas/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Interleucina-1beta/genética , Microdissecção e Captura a Laser , Lipopolissacarídeos/farmacologia , Masculino , Mucina-4/genética , Proteínas Proto-Oncogênicas c-fos/genética , Ratos , Ratos Wistar , Receptores de Somatostatina/genética , Células Estromais/metabolismoRESUMO
BACKGROUND: Dyslipidemia increases circulating levels of oxidized low-density lipoprotein (OxLDL) and this may induce alveolar bone loss through toll-like receptor (TLR) 2 and 4. The purpose of this study was to investigate the effects of dyslipidemia on osteoclast differentiation associated with TLR2 and TLR4 in periodontal tissues using a rat dyslipidemia (apolipoprotein E deficient) model. METHODS: Levels of plasma OxLDL, and the cholesterol and phospholipid profiles in plasma lipoproteins were compared between apolipoprotein E-deficient rats (16-week-old males) and wild-type (control) rats. In the periodontal tissue, we evaluated the changes in TLR2, TLR4, receptor activator of nuclear factor kappa B ligand (RANKL) and tartrate resistant acid phosphatase (TRAP) expression. RESULTS: Apolipoprotein E-deficient rats showed higher plasma levels of OxLDL than control rats (p<0.05), with higher plasma levels of total cholesterol (p<0.05) and LDL-cholesterol (p<0.05) and lower plasma levels of high-density lipoprotein cholesterol (p<0.05). Their periodontal tissue also exhibited a higher ratio of RANKL-positive cells and a higher number of TRAP-positive osteoclasts than control rats (p<0.05). Furthermore, periodontal gene expression of TLR2, TLR4 and RANKL was higher in apolipoprotein E-deficient rats than in control rats (p<0.05). CONCLUSION: These findings underscore the important role for TLR2 and TLR4 in mediating the osteoclast differentiation on alveolar bone response to dyslipidemia.
Assuntos
Perda do Osso Alveolar/genética , Apolipoproteínas E/deficiência , Dislipidemias/genética , Periodonto/metabolismo , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Fosfatase Ácida/genética , Fosfatase Ácida/metabolismo , Perda do Osso Alveolar/sangue , Perda do Osso Alveolar/patologia , Animais , Apolipoproteínas E/genética , Diferenciação Celular , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/patologia , Regulação da Expressão Gênica , Isoenzimas/genética , Isoenzimas/metabolismo , Lipoproteínas LDL/sangue , Masculino , Osteoclastos/metabolismo , Osteoclastos/patologia , Periodonto/patologia , Ligante RANK/genética , Ligante RANK/metabolismo , Ratos , Ratos Transgênicos , Transdução de Sinais , Fosfatase Ácida Resistente a Tartarato , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
PURPOSE: Periodontal disease in pregnant women, evaluated by probing pocket depth (PPD) or clinical attachment level (CAL), significantly increases the risk of subsequent preterm birth (PB) and/or low birth weight (LBW). However, PPD and CAL do not always reflect current periodontal tissue inflammation. Therefore, assessment of bleeding on probing index (BOP), an indicator of periodontal inflammation, may be appropriate. The objective of this cross-sectional study was to investigate the relationship between periodontal inflammation and fetal growth in pregnant women after periodontal treatment. METHODS: We recruited 203 pregnant women (mean age 31.8 ± 4.5 years), including 20 subjects with periodontal inflammation and 183 periodontally healthy controls, after periodontal treatment. Fetal growth parameters as well as periodontal conditions were recorded. RESULTS: Perinatal gestational age was 39.4 ± 1.3 weeks; 8 subjects had a PB and 12 had an infant with a LBW. Results of multiple stepwise regression analysis indicated that birth length was negatively correlated with BOP% (ß = -0.175; p = 0.002). Fetal femur length, and birth length and weight among mothers with low periodontal inflammation were significantly higher than those among mothers with high periodontal inflammation (p < 0.05). The LBW rate in the high periodontal inflammation group was significantly higher than that in the low periodontal inflammation group (p < 0.05). CONCLUSIONS: These results suggest that periodontal inflammation is correlated with fetal femur length, birth weight, and birth length.
Assuntos
Desenvolvimento Fetal , Periodontite/complicações , Complicações na Gravidez , Adulto , Peso ao Nascer , Pressão Sanguínea , Estatura , Estudos Transversais , Diagnóstico Bucal , Feminino , Fêmur/embriologia , Idade Gestacional , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Doenças Periodontais/complicações , Doenças Periodontais/microbiologia , Gravidez , Resultado da Gravidez , Nascimento Prematuro , Fatores de RiscoRESUMO
BACKGROUND: Self-rated oral health is a valid and useful summary indicator of overall oral health status and quality of life. However, few studies on perception of oral health have been conducted among Japanese young adults. This study investigated whether oral health behavior, subjective oral symptoms, or clinical oral status were associated with self-rated oral health in Japanese young adults. METHODS: This cross-sectional survey included 2,087 students (1,183 males, 904 females), aged 18 and 19 years, at Okayama University, Japan. A self-administered questionnaire was distributed and an oral examination was performed. RESULTS: In a structural equation modeling analysis, the score of decayed, missing and filled teeth (DMFT) significantly affected self-rated oral health (p <0.05) and the effect size was highest. Malocclusion, subjective symptoms of temporomandibular disorders (TMD) and stomatitis, and poor oral health behavior significantly induced self-rated poor oral health with small effect sizes (p <0.05). Clinical periodontal conditions and Oral Hygiene Index-simplified were not related to self-rated oral health. CONCLUSION: Self-rated oral health was influenced by subjective symptoms of TMD and stomatitis, oral health behavior, the score of DMFT, and malocclusion. The evaluation of these parameters may be a useful approach in routine dental examination to improve self-rated oral health in university students.
Assuntos
Comportamentos Relacionados com a Saúde , Doenças da Boca/classificação , Saúde Bucal , Autoimagem , Doenças Dentárias/classificação , Adolescente , Atitude Frente a Saúde , Cariostáticos/uso terapêutico , Estudos Transversais , Índice CPO , Assistência Odontológica , Feminino , Fluoretos Tópicos/uso terapêutico , Humanos , Japão , Masculino , Má Oclusão/classificação , Índice de Higiene Oral , Índice Periodontal , Estomatite Aftosa/classificação , Transtornos da Articulação Temporomandibular/diagnóstico , Escovação Dentária , Universidades , Adulto JovemRESUMO
Oral microbiota play a pivotal role in maintaining homeostasis, safeguarding the oral cavity, and preventing the onset of disease. Oral dysbiosis has the potential to trigger pro-inflammatory effects and immune dysregulation, which can have a negative impact on systemic health. It is regarded as a key etiological factor for periodontitis. The emergence and persistence of oral dysbiosis have been demonstrated to mediate inflammatory pathology locally and at distant sites. The heightened inflammation observed in oral dysbiosis is dependent upon the secretion of interleukin-17A (IL-17A) by various innate and adaptive immune cells. IL-17A has been found to play a significant role in host defense mechanisms by inducing antibacterial peptides, recruiting neutrophils, and promoting local inflammation via cytokines and chemokines. This review seeks to present the current knowledge on oral dysbiosis and its prevention, as well as the underlying role of IL-17A in periodontitis induced by oral dysbiosis and its impact on systemic inflammatory disease.
RESUMO
Some studies have reported a significant association between periodontal condition and obesity status. We hypothesized that visceral fat area (VFA) and subcutaneous fat area (SFA) volumes might be correlated with periodontal condition. The purpose of the present cross-sectional study was to investigate the association between periodontal condition and fat distribution in Japanese adults. A total of 158 participants, aged 35-74 years, underwent a health check-up including fat distribution and oral examinations. All of the participants underwent magnetic resonance imaging to quantify VFA and SFA. Periodontal condition was evaluated using the periodontal pocket depth (PPD) and clinical attachment level. The VFA volumes differed among the PPD score and clinical attachment level (CAL) code groups. On the other hand, no significant differences in SFA volume were observed among different periodontal conditions. Multiple regression analysis showed that VFA was positively correlated with a greater CAL (standardized coefficient ß = 0.123, p = 0.009), but not with a greater PPD score. A larger VFA was positively associated with a greater CAL in Japanese adults, whereas no association was found between SFA and periodontal condition.