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dc.contributor.advisorCrotti, Tania-
dc.contributor.authorWilliams, Bonnie Maureen-
dc.description.abstractRheumatoid arthritis (RA) is a chronic autoimmune condition, affecting approximately 1% of the population. RA is characterised by a chronic inflammatory response resulting in destruction of soft and hard tissues within the synovial joints. Disease progression in RA is complex, with multiple signalling pathways identified as crucial to T-cell mediated inflammation and increased osteoclastogenesis in the progression of joint destruction. Cell-adhesion molecules and alterations in apoptotic and autophagic pathways in cells located in the synovial joints have recently emerged as key components of the progression of inflammation and bone destruction in RA. Despite the growing knowledge of these mechanisms, control of bone destruction is still challenging and the prognosis of joint pain is often poor despite optimal control of inflammation. For this reason, it is imperative to utilise appropriate cell culture and in vivo models to identify key signalling pathways and develop targeted therapeutics that may inhibit inflammation, bone destruction and pain concomitantly upon diagnosis or prior to the onset of visible symptoms. The aim of this research was to use in vitro human osteoclast assays in conjunction with a modified collagen-antibody induced arthritis (CAIA) murine model of inflammatory arthritis to determine the effects of emerging novel compounds on inflammation, bone loss and pain-like behaviour. These studies also explored the pathology and progression of pain in a mild and moderate form of the CAIA model whilst extending micro-computed tomography analysis to include assessment of local inflammation and bone volume in the hind paws. The results of these studies support that novel compounds targeting cell adhesion molecules and NF-kB intracellular signalling have the potential to treat inflammatory induced bone loss. The findings presented also highlight the complex mechanisms associated with progression of joint destruction and pain-like behaviour in inflammatory arthritis. Further studies are necessary to elucidate the specific roles of each novel compound and further test the effectiveness of these compounds as potential therapies for RA.en
dc.subjectRheumatoid arthritisen
dc.titlePharmacological Modulation of Inflammation, Bone Loss and Pain in a Murine Model of Inflammatory Arthritisen
dc.contributor.schoolAdelaide Medical Schoolen
dc.provenanceThis electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at:
dc.description.dissertationThesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2019en
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