The Role Of Inflammation In A New Rabbit Model Of Post-Traumatic Osteoarthritis
| atmire.migration.oldid | 1976 | |
| dc.contributor.advisor | Frank, Cyril | |
| dc.contributor.author | Huebner, Kyla | |
| dc.date.accessioned | 2014-04-04T16:23:54Z | |
| dc.date.available | 2014-06-17T07:00:20Z | |
| dc.date.issued | 2014-04-04 | |
| dc.date.submitted | 2014 | en |
| dc.description.abstract | Osteoarthritis (OA) is a debilitating chronic disease. A significant proportion of the population suffering from OA develop it post-injury. This is particularly worrisome as this population is often young, and current interventions do little to prevent or delay the development of OA. Anterior cruciate ligaments (ACL) are commonly damaged during injuries, and reconstruction fails to prevent subsequent development of OA. Many studies are assessing mechanical changes to the joint after injury as the cause of OA; however, if mechanics are maintained after surgical intervention, biological changes in the joint must be contributing to the development of OA. Inflammation has become an area of interest in the pathogenesis of OA. There is little understanding of the pathophysiology of the development of post-traumatic OA (PTOA) and without this, few interventions will be successful in preventing OA. Using a novel animal model of PTOA developed and validated for this purpose, which produced no gross mechanical instability, I tested the hypothesis that after an isolated intra-articular bone injury, inflammation is critical in the development of PTOA. The major findings of this dissertation confirm this central hypothesis and are as follows: First, intra-articular drill holes reproducibly result in cartilage damage as seen in OA without gross mechanical instability. Second, the use of intra-articular glucocorticoids inhibits inflammation and prevents cartilage damage in this model, confirming the role of inflammation in causing damage. Third, IL-1Ra partially inhibits synovial and fat pad inflammation and partially protects articular cartilage. Fourth, feG which inhibits leukocyte migration is ineffective in inhibiting joint inflammation and cartilage damage, suggesting leukocyte migration alone is not a major factor in OA. These studies suggest that PTOA has a significant inflammatory component resulting in cartilage damage. While my work suggests that post-injury use of glucocorticoids may have a role in inhibiting cartilage damage, further study of the specific inflammatory mechanisms and the use of more targeted anti-inflammatory treatments will elucidate better management of joint injuries and provide a framework for not only better understanding PTOA, but for preventing its development. | en_US |
| dc.description.embargoterms | indefinite | en_US |
| dc.identifier.citation | Huebner, K. (2014). The Role Of Inflammation In A New Rabbit Model Of Post-Traumatic Osteoarthritis (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28326 | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/28326 | |
| dc.identifier.uri | http://hdl.handle.net/11023/1404 | |
| dc.language.iso | eng | |
| dc.publisher.faculty | Graduate Studies | |
| dc.publisher.institution | University of Calgary | en |
| dc.publisher.place | Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | |
| dc.subject | Biophysics--Medical | |
| dc.subject | Medicine and Surgery | |
| dc.subject.classification | Osteoarthritis | en_US |
| dc.subject.classification | Inflammation | en_US |
| dc.subject.classification | Dexamethason | en_US |
| dc.subject.classification | Knee | en_US |
| dc.subject.classification | Orthopedics | en_US |
| dc.title | The Role Of Inflammation In A New Rabbit Model Of Post-Traumatic Osteoarthritis | |
| dc.type | doctoral thesis | |
| thesis.degree.discipline | Medical Science | |
| thesis.degree.grantor | University of Calgary | |
| thesis.degree.name | Doctor of Philosophy (PhD) | |
| ucalgary.item.requestcopy | true |