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dc.contributor.authorBlaker, Carina Louise
dc.date.accessioned2019-02-12T02:36:34Z
dc.date.available2019-02-12T02:36:34Z
dc.date.issued2018-09-30
dc.identifier.urihttp://hdl.handle.net/2123/19983
dc.description.abstractPost-traumatic osteoarthritis (PTOA) accounts for approximately 12% of all lower limb OA. Compared to other OA-phenotypes PTOA has the advantage of a known initiating event/time, enabling early identification of at-risk patients. However, with only ~50% of those with apparently similar joint injuries progressing to PTOA, one of the challenges in the field is defining the factors which separate progressors from non-progressors. Do these factors involve tissue-specific injury; biomechanical instability; or the impact trauma at the time of injury? The aims of this thesis were to investigate the role of injury mechanism on the progression of PTOA through the assessment of structural, symptomatic and biomechanical changes in three mouse models of knee injury: (1) surgical ACL transection (ACLT: joint instability, no impact trauma), (2) mechanical ACL rupture (ACLR: joint instability plus a single impact trauma) and (3) sub-critical knee injury (no joint instability, single impact trauma). The two mouse models of ACL injury (ACLT, ACLR) replicated variable PTOA risk seen in patients. Similar to ACL injured patients, joint instability and symptoms (pain/sensitization) were not related to tissue-specific pathologies or structural PTOA progression. Specific tissue pathologies and their associations were identified in the more progressive ACLR model, aligning with OA-cartilage risk factors in patients: synovial inflammation, subchondral bone remodelling, and meniscal pathology. The interaction of OA pathology both within and between knee compartments was found to be dependent on injury mechanism, but not instability or pain. The role and consequences of loading history in joint degeneration was explored in the sub-critical joint injury model. While a single loading event did not induce PTOA, it resulted in focal osteochondral lesions, reduced ACL strength, and altered joint sensitisation. The results of this thesis highlight the importance of joint injury mechanism on PTOA risk, defining key injury- and compartment-specific joint tissue pathology associations, and identifying sub-critical injuries as risk factors for both critical injury and subsequent PTOA.en_AU
dc.publisherUniversity of Sydneyen_AU
dc.publisherFaculty of Medicine and Healthen_AU
dc.publisherKolling Institute of Medical Researchen_AU
dc.rightsThe author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.en_AU
dc.subjectOsteoarthritisen_AU
dc.subjectAnimal Modelsen_AU
dc.subjectKnee Injuryen_AU
dc.subjectACLen_AU
dc.subjectJoint Biomechanicsen_AU
dc.subjectPainen_AU
dc.titleTHE IMPACT OF JOINT INJURY Understanding the Role of Injury Mechanism in the Structural and Symptomatic Progression of Osteoarthritis Using Mouse Models of Knee Injuryen_AU
dc.typePhD Doctorateen_AU
dc.type.pubtypeDoctor of Philosophy Ph.D.en_AU
dc.description.disclaimerAccess is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.en_AU


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