Intervertebral Disc Inflammation: The Effect Of Il-1ra Deficiency On Development, Aging And Injury Of The Murine Caudal Intervertebral Disc

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dc.contributor.advisorMatyas, John
dc.contributor.authorSwamy, Ganesh
dc.contributor.committeememberSalo, Paul
dc.contributor.committeememberJirik, Frank
dc.contributor.committeememberDuncan, Neil
dc.date2018-02
dc.date.accessioned2018-01-31T22:57:19Z
dc.date.available2018-01-31T22:57:19Z
dc.date.issued2018-01
dc.description.abstractIntervertebral disc inflammation: The effect of IL-1Ra deficiency on development, aging and injury of the murine caudal intervertebral disc Inflammation is a coordinated, balanced and redundant cellular response to threats to homeostasis, and leads to tissue repair and regeneration. In the musculoskeletal system, inflammation is central in such reparative processes as fracture healing and wound repair. Inflammation in the intervertebral disc has been broadly implicated in mainly catabolic or degenerative cellular and matrix processes, and cited as the driver of intervertebral disc (IVD) degeneration. We pursued the hypothesis that increased IL-1 activity accelerates the natural history of IVD degeneration. In this study, we assembled a multi-modal platform to evaluate murine caudal IVD structure (through structured histomorphometry and stereology) and function (through dynamic and elastic biomechanics). We also examined gene expression of whole murine IVD (through QPCR analysis) to evaluate IVD response patterns and localized inflammatory gene expression (through immunohistochemistry). Through detailed study of structure, function and molecular response in vivo, the role of inflammation was contrasted between natural aging in genetically normal mice, mice deficient in IL-1Ra, and in both genotypes in the well-characterized pinprick model. In the first set of investigations, we characterized normal aging of the C57BL/6J caudal IVD, from age 3 to 36 months. In the second set of investigations, we characterized the natural history of IVD changes in the IL-1Ra (-/-) mouse on a C57BL/6J background. In our last set of investigations, we examined the effect of injury via the caudal pinprick injury. When synthesized, there is a predictable structure and functional change in aging caudal IVDs, which is accelerated in IL-1Ra (-/-) mice. Inflammatory gene expression is co-regulated with antagonist genes in the IVD. Despite marked changes in gene expression profiles in injury, wild-type and IL-1Ra (-/-) mice demonstrate similar structural and functional changes. The studies described herein have served to increase the importance of IL-1 related inflammation as a driver of degenerative changes in the IVD, and set the stage for further mechanistic analyses.en_US
dc.identifier.citationSwamy, G. (2018). Intervertebral Disc Inflammation: The Effect Of Il-1ra Deficiency On Development, Aging And Injury Of The Murine Caudal Intervertebral Disc (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/5449en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/5449
dc.identifier.urihttp://hdl.handle.net/1880/106368
dc.language.isoeng
dc.publisher.facultyCumming School of Medicine
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity 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.classificationMedicine and Surgeryen_US
dc.titleIntervertebral Disc Inflammation: The Effect Of Il-1ra Deficiency On Development, Aging And Injury Of The Murine Caudal Intervertebral Disc
dc.typedoctoral thesis
thesis.degree.disciplineMedical Science
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
ucalgary.thesis.checklistI confirm that I have submitted all of the required forms to Faculty of Graduate Studies.en_US
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