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1.
Sci Rep ; 12(1): 4094, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260755

RESUMO

Residual ridge resorption (RRR) is a chronic and progressive bone resorption following tooth loss. It causes deterioration of the oral environments and leads to the pathogenesis of various systemic diseases. However, the molecular mechanisms and risk factors for RRR progression are still unclear and controversial. In this study, we developed a tooth extraction model using mice for analyzing long-term morphological and gene expression changes in the alveolar bone. We further applied ovariectomy to this model to elucidate the effects of osteoporosis on RRR progression. As a result, the alveolar bone loss was biphasic and consisted of rapid loss in the early stages and subsequently slow and sustained bone loss over a long period. Histological analysis indicated that ovariectomy prolonged the activation of osteoclasts in the alveolar bone. Furthermore, the expressions of Tnfsf11 and Sema4d kept increasing for a long time in OVX mice. Administration of neutralization antibodies for receptor activator of NF-κB ligand (RANKL) effectively suppressed RRR. Similarly, inhibition of Semaphorin 4D (Sema4D) also improved alveolar bone loss. This study demonstrated that reduced ovarian function may be a risk factor for RRR and that RANKL and Sema4D suppression are potential treatments.


Assuntos
Perda do Osso Alveolar , Conservadores da Densidade Óssea , Reabsorção Óssea , Semaforinas , Perda do Osso Alveolar/patologia , Animais , Antígenos CD/metabolismo , Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/metabolismo , Feminino , Humanos , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Osteoclastos/metabolismo , Osteogênese , Ovariectomia/efeitos adversos , Ligante RANK/metabolismo , Semaforinas/genética , Semaforinas/metabolismo
2.
Clin Implant Dent Relat Res ; 24(1): 83-93, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35019228

RESUMO

BACKGROUND: There have been several reports about the prognosis of teeth adjacent to edentulous spaces for implant-supported fixed prostheses (ISFPs) and removable partial dentures (RPDs). However, there are few reports about the prognosis of the other remaining teeth comparing ISFPs with RPDs. PURPOSE: The aim of this study was to evaluate and compare the prognosis of the remaining teeth for ISFPs and RPDs in terms of survival and complication-free rates. METHODS: Subjects were partially edentulous patients with ISFPs or RPDs inserted in 2003-2016. Teeth adjacent to edentulous spaces (A-teeth), teeth not adjacent to edentulous spaces (R-teeth), and teeth opposing edentulous spaces (O-teeth) were investigated. The endpoints were tooth extraction and complications. A multivariate cox regression model was used to estimate the risk factors for survival of the investigated teeth. RESULTS: A total of 233 (ISFP: 89, RPD: 144) patients were included in the statistical analyses. An IFSP prosthesis, when compared to an RPD prosthesis did not significantly decrease the tooth loss rate for A-teeth (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.30-1.92), for R-teeth (HR: 0.54; 95% CI: 0.28-1.05), or for O-teeth (HR: 0.45; 95% CI: 0.10-2.09). CONCLUSIONS: In partially edentulous spaces, the difference between ISFPs and RPDs does not affect the prognosis of teeth adjacent to edentulous spaces, teeth not adjacent to edentulous spaces, and teeth opposing edentulous spaces. Namely, our findings suggest that it depends largely on the tooth type, jaw, endodontic therapy performed, not on the type of prostheses.


Assuntos
Implantes Dentários , Prótese Parcial Removível , Arcada Parcialmente Edêntula , Prótese Dentária Fixada por Implante/efeitos adversos , Humanos , Prognóstico , Estudos Retrospectivos
3.
FASEB J ; 35(5): e21420, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33774855

RESUMO

Although an aberrant reduction in pancreatic ß-cell mass contributes to the pathogenesis of diabetes, the mechanism underlying the regulation of ß-cell mass is poorly understood. Here, we show that diacylglycerol kinase δ (DGKδ) is a key enzyme in the regulation of ß-cell mass. DGKδ expression was detected in the nucleus of ß-cells. We developed ß-cell-specific DGKδ knockout (ßDGKδ KO) mice, which showed lower blood glucose, higher plasma insulin levels, and better glucose tolerance compared to control mice. Moreover, an increased number of small islets and Ki-67-positive islet cells, as well as elevated cyclin B1 expression in the islets, were detected in the pancreas of ßDGKδ KO mice. DGKδ knockdown in the ß-cell line MIN6 induced significant increases in bromodeoxyuridine (BrdU) incorporation and cyclin B1 expression. Finally, we confirmed that streptozotocin-induced hyperglycemia and ß-cell loss were alleviated in ßDGKδ KO mice. Thus, suppressing the expression or enzymatic activity of DGKδ that functions as a suppressor of ß-cell proliferation could be a novel therapeutic approach to increase ß-cell mass for the treatment of diabetes.


Assuntos
Encéfalo/enzimologia , Proliferação de Células , Diabetes Mellitus Experimental/complicações , Diacilglicerol Quinase/fisiologia , Hiperglicemia/prevenção & controle , Células Secretoras de Insulina/metabolismo , Animais , Hiperglicemia/etiologia , Hiperglicemia/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais
4.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(7): 1031-1038, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30980919

RESUMO

Decreased levels of the δ isozyme of diacylglycerol kinase (DGK) in skeletal muscle attenuate glucose uptake and, consequently, are critical for the pathogenesis of type 2 diabetes. We recently found that free myristic acid (14:0), but not free palmitic acid (16:0), increased the DGKδ protein levels and enhanced glucose uptake in C2C12 myotube cells. However, it has been unclear how myristic acid regulates the level of DGKδ2 protein. In the present study, we characterized the myristic acid-dependent increase of DGKδ protein. A cycloheximide chase assay demonstrated that myristic acid, but not palmitic acid, markedly stabilized DGKδ protein. Moreover, other DGK isozymes, DGKη and ζ, as well as glucose uptake-related proteins, such as protein kinase C (PKC) α, PKCζ, Akt and glycogen synthase kinase 3ß, failed to be stabilized by myristic acid. Furthermore, DGKδ was not stabilized in cultured hepatocellular carcinoma cells, pancreas carcinoma cells or neuroblastoma cells, and only a moderate stabilizing effect was observed in embryonic kidney cells. A proteasome inhibitor and a lysosome inhibitor, MG132 and chloroquine, respectively, partly inhibited DGKδ degradation, suggesting that myristic acid prevents, at least in part, the degradation of DGKδ by the ubiquitin-proteasome system and the autophagy-lysosome pathway. Overall, these results strongly suggest that myristic acid attenuates DGKδ protein degradation in skeletal muscle cells and that this attenuation is fatty acid-, protein- and cell line-specific. These new findings provide novel insights into the molecular mechanisms of the pathogenesis of type 2 diabetes mellitus.


Assuntos
Diacilglicerol Quinase/metabolismo , Músculo Esquelético/citologia , Ácido Mirístico/farmacologia , Estabilidade Proteica/efeitos dos fármacos , Animais , Linhagem Celular , Diabetes Mellitus Tipo 2/etiologia , Glucose/farmacocinética , Humanos , Isoenzimas/metabolismo , Camundongos , Músculo Esquelético/metabolismo , Proteólise/efeitos dos fármacos
5.
Diabetologia ; 60(10): 2076-2083, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28707095

RESUMO

AIMS/HYPOTHESIS: Previously, we demonstrated that myristic acid (14:0) increases levels of diacylglycerol kinase (DGK) δ, a key enzyme involved in type 2 diabetes exacerbation, and enhances glucose uptake in C2C12 myotube cells. Moreover, results from a population-based cohort study suggest that consumption of high-fat dairy products, which contain high amounts of myristic acid, is associated with a lower risk of developing type 2 diabetes. Taken together, we hypothesised that intake of myristic acid reduces type 2 diabetes risk in vivo. The aim of this study was to examine the glucose-lowering effect of myristic acid in Nagoya-Shibata-Yasuda (NSY) mice, a spontaneous model for studying obesity-related type 2 diabetes. METHODS: Male NSY mice were orally administered vehicle (n = 9), 300 mg/kg of myristic acid (n = 14) or 300 mg/kg of palmitic acid (16:0) (n = 9) every other day from 4 weeks of age. Glucose and insulin tolerance tests were performed at weeks 18, 24 and 30, and weeks 20 and 26, respectively. DGKδ levels were measured in skeletal muscle from 32-36-week-old NSY mice via western blot. RESULTS: Chronic oral administration of myristic acid ameliorated glucose tolerance (24-28% decrease in blood glucose levels during glucose tolerance tests) and reduced insulin-responsive blood glucose levels (~20% decrease) in male NSY mice compared with vehicle and palmitic acid groups at 24-30 weeks of age (the age at which the severity of type 2 diabetes is exacerbated in NSY mice). Myristic acid also attenuated the increase in body weight seen in NSY mice. Furthermore, the fatty acid increased DGKδ levels (~1.6-fold) in skeletal muscle of NSY mice. CONCLUSIONS/INTERPRETATION: These results suggest that the chronic oral administration of myristic acid improves hyperglycaemia by decreasing insulin-responsive glucose levels and reducing body weight, and that the fatty acid accounts for the diabetes protective properties of high-fat dairy products. Myristic acid is a potential candidate for the prevention and treatment of type 2 diabetes mellitus and its related diseases.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Ácido Mirístico/uso terapêutico , Animais , Diabetes Mellitus Tipo 2/sangue , Diacilglicerol Quinase/metabolismo , Hiperglicemia/sangue , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Ácido Mirístico/farmacologia , Resultado do Tratamento
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