Master of Science
Musculoskeletal Health Research
Osteoarthritis (OA) is a heterogeneous disease, differentiated based by risk factors that drive joint damage. Peroxisome proliferator-activated receptor delta (PPARd) is a nuclear receptor previously implicated in cartilage damage in OA. Given its deleterious role in post-traumatic OA and in regulating metabolism, we hypothesized that PPARd inhibition will protect against obesity-associated OA. Diet-induced obesity was used to induce OA in mice. Mice fed the western diet for 40 weeks exhibited mild OA, with subchondral bone remodelling occurring alongside cartilage damage. Cartilage-specific Ppard knockout (KO) mice were generated to study its role in metabolic OA. Both wildtype and PPARd KO mice developed severe cartilage damage after 50 weeks on the western diet. Additionally, cartilage-expressed PPARd may play a role in mediating Prg4 expression in the liver. Altogether these data were not able to support the hypothesis but instead emphasized the context-dependent role of PPARd in obesity-associated OA.
Summary for Lay Audience
Osteoarthritis (OA) is a degenerative joint disease that directly impacts over 10% of the North American adult population and is responsible for an increasing financial drain on the economy. Currently, the pathophysiology of OA is not fully understood, and treatment is focused upon suppression of present symptoms. Along with aging, injury and genetics, obesity has been identified as one of the main risk factors for OA. Peroxisome proliferator-activated receptor delta (PPARd) is a protein that is known to play a role in both metabolism and skeletal tissue health. This study aims to understand the role of PPARd in obesity-associated OA by comparing transgenic mouse models fed either normal or high-fat diets. By examining these models using histological techniques, this study will enhance our understanding of cellular mechanisms that promote the onset OA and potentially identify PPARd as a therapeutic target for the disease.
To, Bethia C., "Investigating the Role of Nuclear Receptor Peroxisome Proliferator-Activated Receptor δ in Obesity-Associated Osteoarthritis" (2020). Electronic Thesis and Dissertation Repository. 6861.