Papel do receptor B1 de cininas na patogênese da periodontite experimental.
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2013
Authors
Gonçalves-Zillo, Thais Oliveira [UNIFESP]
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Pesquero, João Bosco [UNIFESP]
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Tese de doutorado
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Abstract
Objetivo: A patogenese da doenca periodontal envolve diferentes aspectos da imunidade e da remodelacao ossea. Assim, o objetivo deste estudo foi avaliar o papel do receptor B1 de cininas (B1R) na periodontite experimental e osteoclastogenese. Material e Metodos: Foi utilizado um modelo experimental de periodontite induzida por ligadura (PEx) em camundongos nocautes para o B1R (B1R-/-) para testar o papel deste receptor na modulacao da perda ossea in vivo. A analise ex vivo dos linfonodos submandibulares confirmou a ativacao do linfocitos T no modelo de ligadura. O efeito autonomo da delecao do B1R foi avaliado em osteoclastos diferenciados a partir de precursores da medula ossea de camundongos. Resultados: Os camundongos B1R-/- exibiram aumento da perda ossea alveolar e aumento da secrecao de interleucina (IL) - 17 ex vivo nos linfonodos submantibulares em resposta a PEx, quando comparados ao animal selvagem (Wt). A analise ex vivo dos linfondos submandibulares revelou niveis de fator de necrose tumoral (TNF)-α reduzidos, enquanto a quantidade de interferon (IFN)-γ permaneceu inalterada. A PEx, entretanto, nao foi capaz de modificar os niveis de IL-10 em animais B1R-/-. Os osteoclastos de camundongos B1R-/- apresentaram aumento do numero de celulas multinucleadas, positivas para a coloracao com a fosfatase acida resistente ao tartrato (TRAP+) quando comparado com o tipo selvagem. O uso de inibidor da enzima conversora de angiotensina, enzima que degrada cininas, como uma estrategia farmacologica para aumentar a disponibilidade de cininas, reduziu a destruicao do osso em ratos e camundongos. Conclusao: Juntos, os nossos resultados indicam que o B1R participa na patogenese da perda ossea induzida por ligadura, demonstrando, assim, o seu papel no desenvolvimento da doenca periodontal.
Aim : The pathophysiology of periodontal diseases involves different aspects of immunity and bone remodeling. Thus, the purpose of this study was to evaluate the role of kinin B1 receptor (B1 R - / - ) in experimental periodontitis and osteoclastogenesis. Material and Methods: Here we used a model of ligature- induced experimental periodontitis (PEx) in mice lacking B1 R (B1 R - / - ) to test the role of this receptor in modulating bone loss in vivo. Ex vivo analysis of submandible lymph nodes were used to confirm T lymphocyte activation. Autonomous effect of B1 R deletion was evaluated in primary osteoclasts precursor from mouse bone marrow. Results: B1 R - / - mice exhibit increased bone loss and increased interleukin (IL) - 17 secretion by lymphnode cells in response to PEx when compared to wild type, whereas tumor necrosis factor (TNF) - α levels were decreased and interferon (IFN)- γ remained unaltered. PEx failed to modify IL - 10 levels in B1 R - / - . Osteoclasts from B1R - / - mice also displayed increased differentiation into functional multinucleated tartrate - resistant acid phosphatase - positive (TRAP+) osteoclasts when compared to wild type. Furthermore, treatment of mice or rats with angiotensin - converting enzyme (ACE) inhibitor, a pharmacological strategy to increase kinin availability once ACE degrades kinins into inactive peptides, could prevent bone destruction. Conclusion: Taken together, our results indicate that B1R participates in the pathogenesis of ligature - induced bone loss, thereby demonstrating its role in the development of periodontal disease
Aim : The pathophysiology of periodontal diseases involves different aspects of immunity and bone remodeling. Thus, the purpose of this study was to evaluate the role of kinin B1 receptor (B1 R - / - ) in experimental periodontitis and osteoclastogenesis. Material and Methods: Here we used a model of ligature- induced experimental periodontitis (PEx) in mice lacking B1 R (B1 R - / - ) to test the role of this receptor in modulating bone loss in vivo. Ex vivo analysis of submandible lymph nodes were used to confirm T lymphocyte activation. Autonomous effect of B1 R deletion was evaluated in primary osteoclasts precursor from mouse bone marrow. Results: B1 R - / - mice exhibit increased bone loss and increased interleukin (IL) - 17 secretion by lymphnode cells in response to PEx when compared to wild type, whereas tumor necrosis factor (TNF) - α levels were decreased and interferon (IFN)- γ remained unaltered. PEx failed to modify IL - 10 levels in B1 R - / - . Osteoclasts from B1R - / - mice also displayed increased differentiation into functional multinucleated tartrate - resistant acid phosphatase - positive (TRAP+) osteoclasts when compared to wild type. Furthermore, treatment of mice or rats with angiotensin - converting enzyme (ACE) inhibitor, a pharmacological strategy to increase kinin availability once ACE degrades kinins into inactive peptides, could prevent bone destruction. Conclusion: Taken together, our results indicate that B1R participates in the pathogenesis of ligature - induced bone loss, thereby demonstrating its role in the development of periodontal disease
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Citation
GONÇALVES-ZILLO, Thais Oliveira. Papel do receptor B1 de cininas na patogênese da periodontite experimental. 2013. 78 f. Tese (Doutorado em Ciências) – Escola Paulista de Medicina, Universidade Federal de São Paulo. São Paulo, 2013.