Fig. 1.
Impaired chondrocyte AMPK and SIRT1 activity disrupts cartilage matrix homeostasis. Aging, inflammation and biomechanical injury in the joint can decrease phosphorylation of AMPKα Thr172 (indicating AMPK activity) and expression of SIRT1 in articular chondrocytes, likely through down-regulation of activity of the major upstream AMPK kinase LKB1 and up-regulation of protein phosphatase PP2Cα, and PTB1B. As a result, the balance between chondrocyte catabolic and anabolic function is disrupted. Overactive chondrocyte catabolic responses ultimately lead to cartilage matrix degradation.