Document Type

Thesis

Degree Name

Master of Science (MSc)

Department

Biology

Program Name/Specialization

Integrative Biology

Faculty/School

Faculty of Science

First Advisor

Stephanie DeWitte-Orr

Advisor Role

Primary advisor

Second Advisor

Diane Gregory

Abstract

Low back pain (LBP) affects up to 80% of the global population at some point during their life. The costs associated with LBP are estimated at $100 billion per year, putting significant strains on our healthcare system. As intervertebral disc (IVD) herniation is one of the major causes of LBP we decided to focus on herniation facilitated inflammatory responses, where damage caused by herniation triggers an innate immune response which likely results in pain, inflammation, and recruitment of specialized innate immune cells like macrophages to the affected area. Since the role of the inflammatory response is relatively uncharacterized in the IVD, the goals of this research were to 1) characterize this early innate immune response by isolating annulus fibrosus (AF) and nucleus pulposus (NP) cells from rat-tail IVDs and growing them in culture, 2) determine the pattern recognition receptors (PRR) repertoire of these cells used to initiate inflammation and 3) identify their ability to mount an inflammatory response following an appropriate damage associated molecular pattern (DAMP) stimulus. Furthermore we determined the effects of this inflammatory response at the tissue level on the biomechanical properties of functional spine units collected from rat-tails. During the course of this experiment we discovered that changes in cytokine production at the cellular level as a result of DAMP stimulation and the resulting inflammatory response had tangible consequences to IVD biomechanics at the tissue level. Injecting discs with 5.0 μg/mL of decorin, while showing no effects 24 hours post injection, resulted in significant increases in IVD compliance 6 days post injection (p=0.016) compared to PBS injected controls. Increased laxity as a result of DAMP mediated inflammation supports our hypothesis of IVD degeneration as a condition of the inflammatory response. This will open new avenues exploring the possibility of novel therapeutics targeting upstream PPRs stopping inflammation before the degenerative cascade takes effect.

Convocation Year

2018

Convocation Season

Fall

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