This study revealed a decreased mitochondrial bioenergetic reserve as a pathogenic factor in degenerative arthropathy and chondrocalcinosis in aging. They evaluated the ATP depletion in chondrocytes together with mitochondrial ultrastructural changes before and during spontaneous knee osteoarthritis (OA) in Hartley guinea pigs and found that nitric oxide (NO) release from knee cartilage was enhanced in OA. NO causes suppression of mitochondrial oxidative phosphorylation to generate ATP through anaerobic glycolysis. The ATP depletion progresses as knee chondrocytes age. Moreover, they also found progressive elevations of chondrocyte ATP-scavenging nucleotide pyrophosphatase/phosphodiesterase (NPP) and its enzymatic en product, both stimulating chondrocalcinosis.