PGC1alpha in cartilage development and osteoarthritis
Anatomy and Physiology
Developmental Biology
Structural Biology
Final Report Abstract
Our detailed study of PGC-1α knockout in cartilage tissue showed altered mitochondrial performance in isolated chondrocytes which got more profound with increasing age. Spare respiratory capacity, and ATP production was significantly decreased in the absence of PGC-1α, while there was no change in mitochondrial mass. However, knockout mice showed only mild and not sustainable effects on cartilage structure during early tissue development including increases growth plate width. However, we found more dramatic consequences during further cartilage development. PGC-1α animals showed profound articular cartilage damage during ageing. OARSI scoring resulted in a significantly increased damage for both knockout lines ( Col2- Cre+/- and AcanCreERT+/-) analyzed in this study compared to control animals. The damage of the four knee joint compartments was accompanied by an intense calcification of the medial collateral ligament as well as by an altered expression pattern of SOX9, β-catenin, and PDK4. Unfortunately, we can not comment on the effect of PGC-1α loss in a post traumatic model of OA. Taken together, our study corroborates the importance of mitochondria activity in cartilage development and maintenance. While, the loss of PGC-1α has low impact on cartilage composition and morphology during early development the compromised chondrocytes mitochondrial performance of knockout chondrocytes showed far-reaching consequences for cartilage maintenance and health, making PGC-1α an interesting target for OA therapy.
