Revealing role of PGC1-alpha in chondrocyte and knee joint health
Abstract
Osteoarthritis is a common chronic disorder of joints which leads to the reduction of articular cartilage and pain. This research depicts the function of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1α) in chondrocytes that maintains mitochondrial function and its role in OA pathogenesis. We analyzed the impact of the PGC1α inhibitor SR-18292 in gene expression and mitochondrial function using immature murine articular chondrocytes (IMACs) in primary culture. There was an important and marked downregulation of mitochondrial-related genes (Esrra, Nrf1, Tfam) in response to SR-18292 treatment, as indicated by quantitative real-time PCR and RNA sequencing studies. Additional fluorescence imaging showed markedly decreased mass and mitochondrial membrane potential. These findings reinforced the premise that PGC1α had a key role in maintenance of mitochondrial health in chondrocytes and that its inhibition may drive OA development.