Date of Award
Master of Science
Dr. Frank Beier
Osteoarthritis (OA) is a degenerative joint disease characteristic of articular cartilage breakdown. Molecular mechanisms of OA are not well understood. Roles of the PPAR6 and AMPK pathways in cartilage have been suggested but are not well defined. We hypothesized that the AMPK and PPAR6 pathways control cartilage ECM turnover by altering chondrocyte gene expression. Mouse primary chondrocytes and adult knee joint explant cultures were treated with either a PPAR5 (GW1516) or an AMPK agonist (AICAR). Cell culture was analyzed by palmitate oxidation assay, MTT assay and Real time PCR. Histological stains and immunohistochemistry were used to analyze explant culture tissues. Changes in gene expression of catabolic factors were demonstrated for both treatments, as well as a decrease in matrix proteoglycan staining. GW1516 also increased fatty acid oxidation, while AICAR decreased cell number. Results indicate involvement of both pathways in early OA changes and suggest that both could be novel therapeutic targets.
LeBlanc, Emily Ann, "PPARÔ AND AMPK PATHWAYS IN CARTILAGE" (2011). Digitized Theses. 3482.