Investigating the Role of Nuclear Receptor Peroxisome Proliferator-Activated Receptor δ in Obesity-Associated Osteoarthritis
Abstract
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.