Medicine and Health Sciences Commons^™

Assessing Inflammation In The Pathology Of Knee Osteoarthritis, Zachary J. Koudys

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a joint disease that causes pain, stiffness, and loss of function. Inflammation of the synovium plays a role in the pathology of OA. Macrophages are the dominant immune cells in synovial tissue. Activated macrophages over-express the translocator protein (TSPO). [¹⁸F]FEPPA is a 2^nd generation positron emission tomography (PET) tracer that can target TSPO with high specificity. Hybrid [¹⁸F]FEPPA PET/MRI may enable accurate quantification of macrophage activity in vivo. In this work, [¹⁸F]FEPPA tracer uptake in knee synovial tissue was measured ex vivo using autoradiography and was validated to correlate to …

Three-Dimensional Ultrasound Imaging For Quantifying Knee Cartilage Volume, Samuel Papernick

Electronic Thesis and Dissertation Repository

Arthritis is the most common chronic health condition in Canada, with the most common form being osteoarthritis (OA). There is a great clinical need for an objective imaging-based point-of-care tool to assess OA status, progression, and response to treatment. This thesis aims to validate a handheld mechanical three-dimensional (3D) ultrasound (US) device against the current clinical standard of magnetic resonance imaging (MRI) for quantifying femoral articular cartilage (FAC) volume. Knee images of 25 healthy volunteers were acquired using 3D US and 3.0 Tesla MRI scans. Two raters manually segmented the trochlear FAC during separate sessions to assess intra- and inter-rater …

Analysis Of Subchondral Bone And Microvessels Using A Novel Vascular Perfusion Contrast Agent And Optimized Dual-Energy Computed Tomography, Justin J. Tse

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA), is a chronic debilitating disease that affects millions of individuals and is characterized by the degeneration of joint subchondral bone and cartilage. These tissue degenerations manifest as joint pain, limited range of joint motion, and overall diminished quality of life. Currently, the exact mechanism(s) and cause(s) by which OA initiates and progresses remain unknown. The multi-factorial complex nature of OA (i.e. age, diabetes, obesity, and prior injuries have all been shown to play a role in OA) contributes to the current lack of a cure or effective long-term treatment for OA.

One re-emerging and interesting hypothesis …

Liver X Receptor And Retinoid X Receptor In Cartilage Development And Homeostasis, Man-Ger Sun

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a heterogeneous and multifactorial degenerative disease characterized by cartilage degradation in the joint. Available treatment options target symptoms but do not address the underlying issue of joint tissue degeneration. A better understanding of the molecular mechanisms maintaining cartilage health is essential for developing novel therapeutic strategies. Previous studies have shown the nuclear receptor Liver X Receptor (LXR) to possess protective roles against cartilage breakdown in OA, however the underlying mechanisms behind this process remain unknown. Since LXR regulates transcription by forming obligate heterodimers with another nuclear receptor, the Retinoid X Receptor (RXR), I hypothesized that LXR and …

Peroxisome Proliferator Activated Receptor Delta In Osteoarthritis, Anusha Ratneswaran

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) affects 1 in 10 Canadians and is a leading cause of mobility disability worldwide. This condition is characterized by cartilage degeneration, subchondral bone damage and inflammation of the synovium, resulting in pain and joint failure. No treatments exist to stop the progression of this disease, and its underlying molecular mechanisms remain largely unknown. We previously identified the peroxisome proliferator activated receptor (PPAR) nuclear receptor pathway as altered in OA cartilage. In-vitro studies identified PPARd as a promoter of catabolic activity in chondrocytes, providing the foundation for my overarching hypothesis that PPARd inhibition is protective in OA.

I commenced …

Epidermal Growth Factor Receptor In Joint Health And Osteoarthritis, Michael A. Pest

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases in the world. Our laboratory has shown that epidermal growth factor receptor (EGFR) signalling is involved in the process of cartilage degeneration in OA. Regulation of EGFR signalling by mitogen-inducible gene 6 (Mig-6) and dual specificity phosphatase 1 (DUSP-1) allows for signal modulation, and mouse models have linked these proteins to joint pathologies. Failure to control EGFR signalling may be involved in OA progression leading to my overarching hypothesis: regulation of EGFR signalling is essential for maintenance of joint health.

I initially tested the role of Mig-6 in cartilage health …