RESUMO
Nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) plays an important role in host defense, as well as in inflammation-induced tissue lesions. Here we evaluated the role of NO in bone loss in bacterial infection-induced apical periodontitis by using iNOS-deficient mice (iNOS(-/-)). The iNOS(-/-) mice developed greater inflammatory cell recruitment and osteolytic lesions than WT mice. Moreover, tartrate-resistant acid-phosphatase-positive (TRAP(+)) osteoclasts were significantly more numerous in iNOS(-/-) mice. Furthermore, the increased bone resorption in iNOS(-/-) mice also correlated with the increased expression of receptor activator NF-kappaB (RANK), stromal-cell-derived factor-1 alpha (SDF-1 alpha/CXCL12), and reduced expression of osteoprotegerin (OPG). These results show that NO deficiency was associated with an imbalance of bone-resorption-modulating factors, leading to severe infection-stimulated bone loss.
Assuntos
Perda do Osso Alveolar/enzimologia , Infecções Bacterianas/enzimologia , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Periodontite Periapical/enzimologia , Fosfatase Ácida/análise , Actinomicose/enzimologia , Perda do Osso Alveolar/patologia , Animais , Infecções por Bacteroidaceae/enzimologia , Biomarcadores/análise , Contagem de Células , Movimento Celular , Quimiocina CXCL12/análise , Exposição da Polpa Dentária/microbiologia , Isoenzimas/análise , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Osteoclastos/patologia , Osteólise/metabolismo , Osteólise/patologia , Osteoprotegerina/análise , Periodontite Periapical/patologia , Ligante RANK/análise , Receptor Ativador de Fator Nuclear kappa-B/análise , Fosfatase Ácida Resistente a TartaratoRESUMO
Proteinase-activated receptor-2 (PAR2) belongs to a novel subfamily of G-protein-coupled receptors with seven-transmembrane domains. This receptor is widely distributed throughout the body and seems to be importantly involved in inflammatory processes. PAR2 can be activated by serine proteases such as trypsin, mast cell tryptase, and bacterial proteases, such as gingipain produced by Porphyromonas gingivalis. This review describes the current stage of knowledge of the possible mechanisms that link PAR2 activation with periodontal disease, and proposes future therapeutic strategies to modulate the host response in the treatment of periodontitis.
Assuntos
Periodontite/enzimologia , Receptor PAR-2/fisiologia , Receptores Ativados por Proteinase/fisiologia , Infecções por Bacteroidaceae/enzimologia , Humanos , Inflamação/enzimologia , Inflamação/fisiopatologia , Periodontite/fisiopatologia , Porphyromonas gingivalis , Receptores Ativados por Proteinase/metabolismoRESUMO
Proteinase-activated receptor-2 (PAR2) belongs to a novel subfamily of G-protein-coupled receptors with seven-transmembrane domains. This receptor is widely distributed throughout the body and seems to be importantly involved in inflammatory processes. PAR2 can be activated by serine proteases such as trypsin, mast cell tryptase, and bacterial proteases, such as gingipain produced by Porphyromonas gingivalis. This review describes the current stage of knowledge of the possible mechanisms that link PAR2 activation with periodontal disease, and proposes future therapeutic strategies to modulate the host response in the treatment of periodontitis.