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dc.contributor.authorReddi, Durga
dc.date.accessioned2015-09-02T12:09:35Z
dc.date.available2015-09-02T12:09:35Z
dc.date.issued2012
dc.identifier.citationReddi, D. 2012. Interactions of Porphyromonas gingivalis with bone marrow cells: implications on mediators of bone resorption. Queen Mary University of Londonen_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/8416
dc.descriptionPhDen_US
dc.description.abstractPeriodontitis is a multi-factorial disease characterised by the loss of connective tissue and underlying alveolar bone leading to the loss of teeth. Porphyromonas gingivalis (P. gingivalis) is a gram-negative black pigmented anaerobe associated with chronic periodontitis. Porphyromonas gingivalis possesses a range of virulence factors including gingipains, lipopolysaccharide (LPS) and fimbriae. Receptor activator of nuclear factor-κB ligand (RANKL) induces bone resorption whilst osteoprotegerin (OPG) blocks this process by binding to RANKL and acting as a decoy receptor. Cyclooxygenase-2 (COX-2) is an enzyme responsible for the synthesis of prostaglandin E2 (PGE2), a potent inflammatory mediator of bone resorption. Mitogen-activated protein kinases (MAPK) are intra-cellular signaling proteins that control fundamental cellular events, with implications in inflammation and bone metabolism. This thesis aimed to investigate the effect of P. gingivalis on bone marrow stromal cells, primarily on the regulation of molecular mechanisms involved in bone resorption, using gene and protein expression assays, and secondarily on changes in their global transcriptional profile, using microarray technology. It was determined that P. gingivalis upregulated RANKL and downregulated OPG gene and protein expression, resulting in an increased RANKL/OPG expression ratio. These regulations were partly attributed to its LPS and an unidentified synergistic factor. PGE2 was a key mediator in this regulation of RANKL expression. Further to this, P. gingivalis was shown to signal through p38 MAPK, contributing to the PGE2-mediated RANKL induction. The extension of this work using microarray technology demonstrated that in the present experimental system P. gingivalis positively regulates a broad spectrum of genes involved in promoting inflammation and bone destruction. This thesis shows that P. gingivalis can exert its virulence on bone marrow stromal cells. An interplay of bacterial and host factors leads to the activation of molecular mechanisms of bone resorption, which may be implicated in initiating periodontal disease. Moreover, the identified mediators of bone resorption may serve as potential targets for treating P. gingivalis-associated periodontitis.en_US
dc.description.sponsorshipBarts and the London Dental Institute (Support for Oral Science Bursary); Research Advisory Board of Barts and the London Charitable Foundation (Start-Up Grant 453/592); University of London Central Research Fund (AR/CRF/B).en_US
dc.language.isoenen_US
dc.publisherQueen Mary University of Londonen_US
dc.subjectDentistryen_US
dc.subjectPeriodontitisen_US
dc.titleInteractions of Porphyromonas gingivalis with bone marrow cells: implications on mediators of bone resorptionen_US
dc.typeThesisen_US
dc.rights.holderThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author


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    Theses Awarded by Queen Mary University of London

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