Role of inducible nitric oxide synthase in porphyromonas gingivalis-induced oral bone loss and in host response to porphyromonas gingivalis infection in murine chamber model
Date
2003
DOI
Authors
Boustani, Gabriel A.
Version
OA Version
Citation
Abstract
Periodontal disease, the leading cause of tooth loss in the adult population, is an inflammatory disease that is triggered by bacteria. Epidemiological and experimental data show that Porphyromonas gingivalis, a gram-negative anaerobic bacterium is a causative agent of periodontal disease. Nitric oxide, a mediator of cardiovascular, homeostatic, neural and immune function, has been implicated in periodontal disease. The purpose of this study was to assess the role of inducible nitric oxide synthase in Porphyromonas gingivalis-induced oral bone loss and in response to murine chamber model infection. In the first study, we used a murine model (C57BL/6 wild type (WT) and knockout (iNOS-KO) iNOS mouse) in which alveolar bone loss is induced ty oral infection with Porphyromonas gingivalis. The results revealed that P. gingivalis-challenged iNOS-KO mice did mt show significant bone loss when compared to unchallenged iNOS-KO animals. In addition, iNOS-KO animals, independent of any bacterial challenge, showed a greater cemento-enamel junction-alveolar bone crest distance. In the second experiment, we investigated the role of iNOS in the host response to P. gingivalis infection using a murine subcutaneous chamber model. Subcutaneous chambers were implanted in 6-week old iNOS-KO, or wild type mice. Animals were then challenged with 5.5xlO [8] CFU of P. gingivalis strain A7436 and observed daily. Chamber fluid samples were collected at days 1, 3, 7, and 11 and analyzed for P. gingivalis (CFU/ml), total inflammatory cell counts, TNF-α, IL-1β, IL-6, and PGE [2] levels and neutrophil-mediated phagocytosis and killing using a fluorescent phagocytosis assay. Gross pathologic evaluation of P. gingivalis challenged iNOS KO mice revealed enhanced lesion formation and chamber rejection as compared to wild type mice at day ll. P. gingivalis counts in chamber fluids of iNOS-KO mice were elevated in comparison to wild type animals. The total number of inflammatory cells was rot significantly different between the groups throughout the study. Fluorescent phagocytosis assay data showed reduced numbers of live PMNs in the iNOS-KO group by day 3, and a concomitant reduction in the percentage of neutrophils associated with P. gingivalis. Similar levels of TNF-α and IL-1β levels in chamber fluids were detected for both groups. Our results provide evidence suggesting that NO is an important factor in limiting Porphyromonas gingivalis infection in a murine subcutaneous chamber model.
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Thesis (M.S.D.)--Boston University, Goldman School of Dental Medicine, 2003 (Periodontology and Oral Biology).
Includes bibliography (leaves 45-56).
Thesis (M.S.D.)--Boston University, Goldman School of Dental Medicine, 2003 (Periodontology and Oral Biology).
Includes bibliography (leaves 45-56).
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This work is protected by copyright. Downloading is restricted to the BU community. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.