990 resultados para Ligante do receptor ativador do fator nuclear
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The Giant Cell Lesions, both the Central Giant Cells Lesions (CGCL) as the Peripheral Giant Cells Lesions (PGCL), correspond to a group of oral lesions that are histologically similar entities; however they show a variable clinical behaviour. The purpose of this study was to compare the immunohistochemical expression of bone resorption factors RANK (Receptor Activator of Nuclear Factor kappa B), RANKL (Receptor Activator of Nuclear Factor kappa B Ligand) and OPG (Osteoprotegerin) between CGCL and PGCL. Additionally, these bone resorption factors were examined in terms of aggressiveness of these lesions. The sample consisted of 61 cases, 30 cases of PGCL and 31 CGCL (16 non-aggressive and 15 aggressive). The analysis was performed by quantification of mononuclear cells (MO) and giant multinucleated cells (CG) immunopositive to anti-RANK, anti-RANKL and anti-OPG antibodies in 10 fields. Moreover, according to the proportion between the amount of cells positive for RANKL and OPG, the cases were categorized into: RANKL>OPG, OPG>RANKL e RANKL=OPG. CGCL showed a higher amount of MO (p=0.002) and total cells (p=0.003) both positives to RANKL compared with the PGCL. Additionally, the CGCL revealed a significant association with the ratio of RANKL>OPG (p=0.001). Analysis of the bone resorption factors revealed no significant differences between aggressive and non-aggressive CGCL (p>0.05). It was observed a positive correlation between the markers themselves, and a negative correlation between lesion size and quantity of OPG positive MO cells (p=0,004) and total cells (p=0,009). Through these results, we suggest that the greatest CGCL resorptive potential compared to the PGCL, may have occurred to the high expression of RANKL. Furthermore differences in the biological behavior of aggressive and non-aggressive CGCL appear to be related to the expression of these bone resorption factors
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The odontogenic keratocysts are distinguished from other odontogenic cystic lesions by their potentially aggressive clinical behavior and association, in some cases, with Gorlin syndrome. Studies have suggested that syndrome keratocysts, in comparison with sporadic lesions, have higher growth and infiltration capacity and higher recurrence tendency. The aim of this study was to analyze, by means of immunohistochemistry, the expressions of receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG), the angiogenic index (CD34) and the presence of myofibroblasts (α-SMA) in primary and recurrent sporadic keratocysts and in keratocysts associated with Gorlin syndrome. The sample was composed by 30 sporadic keratocysts (22 primary and 8 recurrent) and 22 syndrome keratocysts. In the epithelium and in the fibrous capsule of the lesions, the immunoexpression of RANKL and OPG was evaluated by determination of the percentage of positive cells, according to the following scores: 0 (less than 10% of positive cells), 1 (11% - 50% of positive cells), 2 (51% - 75% of positive cells) and 3 (more than 76% of positive cells). In addition, cases were classified according to the RANKL score/ OPG score ratio, as follows: RANKL > OPG, RANKL < OPG, and RANKL = OPG. The angiogenic index was analyzed by counting the microvessels immunoreactive to anti-CD34 antibody in 5 fields (200). The analysis of myofibroblasts was performed by counting the cells immunoreactive to anti-α-SMA antibody in 10 fields (400). The analysis of the expressions of RANKL and OPG in the epithelial lining and in the fibrous capsule did not reveal significant differences between groups (p > 0.05). Regarding the RANKL/ OPG ratio in the epithelial lining, most sporadic primary (54.5%) and syndrome lesions (59.1%) showed RANKL < OPG ratio and RANKL = OPG ratio, respectively (p > 0.05). With respect to the RANKL/ OPG ratio in the fibrous capsule, the majority of sporadic primary (81.8%) and sporadic recurrent lesions (75.0%) and most syndrome lesions (45.5%) showed RANKL = OPG ratio (p > 0.05). The mean number of microvessels was 69.2 in sporadic primary lesions, 67.6 in recurrent lesions, and 71.6 in syndrome lesions, with no significant differences between groups (p > 0.05). The mean number of myofibroblasts was 34.4 in sporadic primary lesions, 29.3 in recurrent lesions, and 33.7 in syndrome lesions, with no significant differences between groups (p > 0.05). In conclusion, the results of the present study suggest that the differences in the biological behavior between sporadic keratocysts and keratocysts associated with Gorlin syndrome may not be related to the expressions of RANKL and OPG, the RANKL/ OPG ratio, the angiogenic index or the number of myofibroblasts in these lesions
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Periodontal disease is an infection initiated by oral periodontal pathogens that trigger an immune response culminating in tissue destruction. This destruction is mediated by the host by inducing the production and activation of lytic enzymes, cytokines and the stimulation of osteoclastogenesis. The aim of this study was to compare the immunohistochemical expression of factors involved in bone resorption, RANKL (Ligand Receptor Activator of Nuclear Factor kappa B), OPG (Osteoprotegerin) and TNF-α (tumor necrosis factor alpha) between the gingival healthy, gingivitis and chronic periodontitis and correlate them with clinical parameters. The sample consisted of 83 cases and 12 clinically healthy gums, 42 gingivitis and 29 periodontitis, from 74 adolescent and adult patients with a mean age of 35 years, without systemic changes and non-smokers, predominantly female and race brown. There was no statistically significant difference for the expression of anti-RANKL (p = 0.581) and RANKL / OPG ratio (p = 0.334) when comparing the three conditions, but the anti-OPG and anti-TNF-α showed statistically significant between the types of injury (p = 0.001 and p <0.001, respectively), showing greatest expression in periodontitis. In cases of periodontitis, the variable clinical attachment loss (PIC) was statistically significant and positive correlation, respectively, with immunostaining of anti-RANKL (p = 0.002, p = 0.001 and r = 0.642), anti-OPG (p = 0.018, p = 0.014 and r = 0.451), anti-TNF-α (p = 0.032, p = 0.014 and r = 0.453) and the percentage ratio of RANKL / OPG (p = 0.018, p = 0.002 and r = 0.544). The tooth mobility (MB) showed a statistically significant difference only with immunohistochemical anti-RANKL (p = 0.026), and probing depth (PD) was positively correlated with anti-RANKL (p = 0.028 and r = 0.409), both in cases of periodontitis. Only in cases of gingivitis TNF-α was positively correlated with RANKL (p = 0.012 and r = 0.384) and the RANKL / OPG ratio (p = 0.027 and r = 0.341). Given these results, we conclude that the greatest expression of TNF-α in periodontitis demonstrates a relationship with the progression and severity of periodontal disease and the correlation between all antibodies and clinical attachment loss demonstrates their involvement in periodontal bone resorption
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Coordenao de Aperfeioamento de Pessoal de Nvel Superior (CAPES)
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Coordenao de Aperfeioamento de Pessoal de Nvel Superior (CAPES)
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Ps-graduao em Cincias Fisiolgicas - FOA
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Conselho Nacional de Desenvolvimento Cientfico e Tecnolgico (CNPq)
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Conselho Nacional de Desenvolvimento Cientfico e Tecnolgico (CNPq)
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Osteoclastogenesis may be regulated via activation of the RANK/RANKL (receptor activator of nuclear factor-kappa B/ receptor activator of nuclear factor-kappa B ligand) system, which is mediated by osteoblasts. However, the bone loss mechanism induced by T3 (triiodothyronine) is still controversial. In this study, osteoblastic lineage rat cells (ROS 17/2.8) were treated with T3 (10(-8) M 10(-9) 10 M, and 10(-10) M), and RANKL mRNA (messenger RNA) expression was measured by semiquantitative RT-PCR. Our results show that T3 concentrations used did not significantly enhance RANKL expression compared to controls without hormone treatment. This data suggests that other mechanisms, unrelated to the RANK/RANKL system, might be to activate osteoclast differentiation in these cells.
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Periodontal diseases, highly prevalent disease in worldwide population, manifest primarily in two distinct entities: plaque-induced gingivitis and periodontitis. Periodontitis is a chronic inflammatory disease characterized of different levels of collagen, cementum, and alveolar bone destruction. Recent experimental studies demonstrated anti-inflammatory and antirreabsortive effect of antihypertensive agents of the angiotensin II receptor blockers class on periodontal disease. The aim of this study was to evaluate the effects of azilsartan (AZT), a potent inhibitor of the angiotensin II receptor which has minimal adverse effects on bone loss, inflammation, and the expression of matrix metallo proteinases (MMPs), receptor activator of nuclear factor kB ligand (RANKL), receptor activator of nuclear factor kB (RANK), osteoprotegerin (OPG), cyclooxygenase-2 (COX-2), and cathepsin K in periodontal tissue in a rat model of ligature-induced periodontitis. Male Wistar albino rats were randomly divided into 5 groups of 20 rats each: (1) nonligated, water; (2) ligated, water; (3) ligated, 1 mg/kg AZT; (4) ligated, 5 mg/kg AZT; and (5) ligated, 10 mg/kg AZT. All groups were treated with water or AZT for 10 days. Periodontal tissues were analyzed by morphometric exam, histopathology and immunohistochemical detection of MMP-2, MMP-9, COX-2, RANKL, RANK, OPG, and cathepsin K. Levels of IL-1b, IL-10, TNF-a, myeloperoxidase (MPO), and glutathione (GSH) were determined by ELISA. Treatment with 5 mg/kg AZT resulted in reduced MPO (p0.05) and IL-1b (p0.05) levels and increased in Il-10 levels (p0.05). It was observed a reduced expression of MMP-2, MMP-9, COX-2, RANK, RANKL, cathepsin K, and a increased expression of OPG in the animals subjected to experimental periodontitis and threated with AZT (5 mg/kg). Conclusions: These findings suggest an anti-inflammatory and anti-reabsortive effects of AZT on ligature-induced periodontitis in rats.
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Coordenao de Aperfeioamento de Pessoal de Nvel Superior (CAPES)
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Dissertao para obteno do grau de Mestre no Instituto Superior de Cincias da Sade Egas Moniz
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Considerando que as doenas cardiovasculares representam a maior causa de mortalidade e morbidade em pases ocidentais, a aterosclerose se destaca pelo fato de predispor os pacientes ao infarto do miocrdio, a acidentes vasculares cerebrais e a doenas vasculares perifricas. Neste contexto, a oxidao de lipoprotenas do plasma, particularmente LDL, um dos fatores de risco para eventos cardiovasculares, pois reconhecida e internalizada por macrfagos, ocasionando a sua diferenciao em foam cells. Diversos fatores participam deste processo de diferenciao, como a expresso de receptores de scavenger CD 36, proporcionando aumento na captao de LDL oxidada, aumento na sntese endgena de colesterol e ativao de fatores nucleares que iniciam a transcrio de protenas especficas e fatores de crescimento que disparam a aterognese. Os fenmenos celulares relacionados apoptose tambm so de especial importncia, tanto no desenvolvimento da leso aterosclertica como na estabilidade da placa e formao de trombos. As prostaglandinas (PGs) ciclopentennicas (CP-PGs), em particular a PGA2 e a 15-desxi-12,14-PGJ2 so uma classe especial de PGs que, em diminutas concentraes, disparam a expresso das protenas de choque trmico (hsp), que so citoprotetoras. Alm disso, CP-PGs bloqueiam a ativao do fator nuclear pr-inflamatrio NF-B tornando-as potentes agentes antiinflamatrios. Embora as PGs das famlias A e J guardem uma srie de caractersticas em comum, a 15-desxi-12,14- PGJ2 o ligante fisiolgico do fator nuclear pr-aterognico PPAR-, enquanto as PGs da famlia A ativam apenas a via citoprotetora das hsp. Este trabalho teve como objetivo avaliar os efeitos das CP-PGs sobre a expresso gnica de fatores relacionados diferenciao de macrfagos em foam cells, bem como protenas reguladoras do processo de apoptose, em clulas da linhagem pr-monoctica humana U937. Para tal, as clulas foram tratadas com CPPGs em presena e/ou ausncia de LDL nat e LDL ox, o RNA foi extrado para a realizao de RT-PCR para PPAR-, CD 36, HMG-CoA redutase e protenas de apoptose Caspase 3, p53 e Bcl-xL. O tratamento estatstico utilizado foi anlise de varincia (ANOVA one-way) e teste t de student, com resultados expressos como mdias + desvios-padro da mdia, com P<0,05. Os resultados obtidos demontraram que as CP-PGs PGA2 (20M-24h) e PGJ2 (1,5M-24h) inibiram a expresso gnica do fator nuclear PPAR- (64 % (PGA2), 88 % (15- d-PGJ2)) nas clulas U937, em presena de LDL oxidada, quando comparado ao controle. PGA2 inibiu a expresso de HMG-CoA redutase (33 %), enzima chave da sntese de colesterol intracelular, e o tratamento com as CP-PGs tambm inibiu a apoptose nas clulas tratadas em presena de LDL oxidada. Os dados sugerem que as CP-PGs apresentam grande potencial para o tratamento da aterosclerose, j que, alm de apresentarem efeito antiinflamatrio, inibem a expresso do fator nuclear pr-aterognico PPAR-, do receptor de scavenger CD36 (apenas a 15-desxi-12,14-PGJ2) e da enzima HMG-CoA redutase. O bloqueio da apoptose nas clulas estudadas pode estar relacionado citoproteo oferecida por estas PGs. Embora investigaes in vivo deste laboratrio tenham mostrado a eficcia do tratamento com CP-PGs em camundongos portadores de aterosclerose, estudos adicionais so necessrios para esclarecer-se o efeito antiaterognico das mesmas.
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Receptor ativador nuclear κappa B (RANK), ligante do receptor ativador nuclear κappa B (RANKL) e osteoprotegerina (OPG) so membros da famlia do fator de necrose tumoral relacionados com o metabolismo sseo. A formao, diferenciao e atividade dos osteoclastos so reguladas por estas trs protenas. RANK um receptor transmembrana presente em diversos tipos celulares, principalmente em clulas de linhagem macrofgica, linfcitos, clulas dendrticas e fibroblastos e quando ativado pelo seu ligante, RANKL, promove a diferenciao e ativao de clulas osteoclsticas responsveis pelo processo de reabsoro ssea. A OPG impede a ligao RANK/RANKL atuando como um receptor inibitrio para a atividade osteoltica. O objetivo deste estudo foi comparar a expresso imuno-histoqumica destes biomarcadores em cistos radiculares (n=20) e cistos dentgeros (n=20). A expresso imuno-histoqumica destes marcadores foi avaliada no epitlio e na cpsula dos cistos por escores e percentuais mdios de imunomarcao. Para o epitlio, a anlise semi-quantitativa revelou um padro similar dos escores de imunomarcao de RANK, RANKL e OPG nas leses, no havendo diferena estatstica significante (p=0.589, p=0.688, p=0.709, respectivamente). Para a cpsula cstica a anlise quantitativa, mostrou diferena estatstica significante entre os percentuais mdios de imunomarcao do RANK e RANKL (p=0,001 e p=0,005, respectivamente) nos cistos. A correlao dos escores de imunomarcao de RANKL e OPG no epitlio do CR e do CD revelou diferena estatstica significante (p=0,029, p=0,003, respectivamente). No epitlio dos CRs e dos CDs observou-se uma maior imunoexpresso da OPG comparada a do RANKL. Os resultados apontam a presena de RANK, RANKL e OPG nos cistos radiculares e cistos dentgeros, sugerindo a atuao destas protenas no desenvolvimento e expanso das leses no osso adjacente
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Coordenao de Aperfeioamento de Pessoal de Nvel Superior (CAPES)
