Fig. 5.

Regulation of chondrocyte autophagy and metabolism by AMPK and mTOR signaling pathways. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a heterotrimeric complex that contains subunits α, β, and γ. LKB1 (liver kinase B1), CAMKK2 (calcium-sensitive kinase) and TAK1 (transforming growth factor-β-activated protein kinase-1) are three major enzymes that can introduce AMPK phosphorylation. In OA chondrocytes, inhibited AMPK phosphorylation decreases ULK1 expression, which is an essential initiator of autophagy. Decreased phosphorylation of AMPK also downregulates the expression of PGC-1α through SIRT-1 in articular chondrocytes, leading to mitochondrial dysfunction