Expressão imuno-hitoquímica das proteínas RANK, RANKL e OPG em cistos radiculares e cistos dentígeros

Receptor ativador nuclear κappa B (RANK), ligante do receptor ativador nuclear κappa B (RANKL) e osteoprotegerina (OPG) são membros da família do fator de necrose tumoral relacionados com o metabolismo ósseo. A formação, diferenciação e atividade dos osteoclastos são reguladas por estas três proteínas. RANK é um receptor transmembrana presente em diversos tipos celulares, principalmente em células de linhagem macrofágica, linfócitos, células dendríticas e fibroblastos e quando ativado pelo seu ligante, RANKL, promove a diferenciação e ativação de células osteoclásticas responsáveis pelo processo de reabsorção óssea. A OPG impede a ligação RANK/RANKL atuando como um receptor inibitório para a atividade osteolítica. O objetivo deste estudo foi comparar a expressão imuno-histoquímica destes biomarcadores em cistos radiculares (n=20) e cistos dentígeros (n=20). A expressão imuno-histoquímica destes marcadores foi avaliada no epitélio e na cápsula dos cistos por escores e percentuais médios de imunomarcação. Para o epitélio, a análise semi-quantitativa revelou um padrão similar dos escores de imunomarcação de RANK, RANKL e OPG nas lesões, não havendo diferença estatística significante (p=0.589, p=0.688, p=0.709, respectivamente). Para a cápsula cística a análise quantitativa, mostrou diferença estatística significante entre os percentuais médios de imunomarcação do RANK e RANKL (p=0,001 e p=0,005, respectivamente) nos cistos. A correlação dos escores de imunomarcação de RANKL e OPG no epitélio do CR e do CD revelou diferença estatística significante (p=0,029, p=0,003, respectivamente). No epitélio dos CRs e dos CDs observou-se uma maior imunoexpressão da OPG comparada a do RANKL. Os resultados apontam a presença de RANK, RANKL e OPG nos cistos radiculares e cistos dentígeros, sugerindo a atuação destas proteínas no desenvolvimento e expansão das lesões no osso adjacente

Exprassão imuno-histoquímica dos fatores de reabsorção óssea em lesões centrais e periféricas de células gigantes

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

Estudo da associação dos genes RANk, RANKL e OPG com a osteopatia diabética

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES

Análise imuno-histoquímica das proteínas RANK, RANKL e OPG em dentes de ratos reimplantados

The RANK / RANKL / OPG sy stem plays an important role in bone formation and resorption . This finding has been regarded as one of the m ost important advances in the understanding of bone biology with respect to osteoclastogenesis. The aim of this study was to investigate the expression of RANKL / RANK / OPG markers in reimplanted t eeth of rats, and to observe the relationship between the expression of these markers and to oth and bone resorption. Thirty male Wistar rats (Rattus norvegicus albinos) had their maxillary right incisors extrac ted , and were divided into 2 groups according to the period that the extracted teeth were kept in dry air before reimplantation : G1 (n = 15) - 5 minutes , and G2 (n = 15) - 60 minutes . After reimplantation, teeth were analyzed at intervals of 1, 3 and 7 da ys. After these experimental periods, the animals were euthanized. Longitudinal sections with 5μm thick were obtained and stained with Hematoxylin and Eosin for histological analysis , while 3μm thick sections were subjected to immunohistochemical analysis of OPG , RANK and RANKL. The results showed that the RANK / RANKL / OPG system actively participates in both the repair process, as well as tooth and bone resorption . Extr a - alveolar time of 60 minutes before replantation caused minor expressions of RANKL a nd OPG, not influencing the expression of RANK; RANKL immunostaining showed higher in both groups when compared to other biomarkers, participating in all phases of bone and tooth resorption; RANKL was associated to both osteoclastogenesis and c ell ular proliferation , and was expressed in both groups.

Efeitos da azilsartana sobre a doença periodontal em um modelo experimental com ratos wistar

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 (p˂0.05) and IL-1b (p˂0.05) levels and increased in Il-10 levels (p˂0.05). 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.