Targeted regulation of FoxO1 in chondrocytes prevents age-related osteoarthritis via autophagy mechanism.

Autophagy is designated as a biological recycling process to maintain cellular homeostasis by the sequestration of damaged proteins and organelles in plasma and cargo delivery to lysosomes for degradation and reclamation. This organelle recycling process promotes chondrocyte homeostasis and has been previously implicated in osteoarthritis (OA). Autophagy is widely involved in regulating chondrocyte degeneration markers such as MMPs, ADAMSTs and Col10 in chondrocytes. The critical autophagy-related (ATG) proteins have now been considered the protective factor against late-onset OA. The current research field proposes that the autophagic pathway is closely related to chondrocyte activity. However, the mechanism is complex yet needs precise elaboration. This review concluded that FoxO1, a forkhead O family protein, which is a decisive mediator of autophagy, facilitates the pathological process of osteoarthritis. Diverse mechanisms regulate the activity of FoxO1 and promote the initiation of autophagy, including the prominent AMPK and Sirt-2 cellular pathways. FoxO1 transactive is regulated by phosphorylation and acetylation processes, which modulates the downstream ATGs expression. Furthermore, FoxO1 induces autophagy by directly interacting with ATGs proteins, which control the formation of autophagosomes and lysosomes fusion. This review will discuss cutting-edge evidence that the FoxO-autophagy pathway plays an essential regulator in the pathogenesis of osteoarthritis.