The Role of Autophagy in Chondrocyte Metabolism and Osteoarthritis: A Comprehensive Research Review

Abstract

Chondrocytes are the sole cellular constituents of normal cartilage. The degeneration and apoptosis of these cells are considered the main cause of osteoarthritis (OA). Previous studies have suggested that the enhancement of autophagy in chondrocytes can delay the progression of osteoarthritis by affecting intracellular metabolic activity, i.e., by regulating the metabolism of nutrients, which can delay cell aging and death. In this review, we explored the relationship between autophagy and chondrocyte metabolism and provided new ideas for the prevention and treatment of OA.

Figure 1

Process and regulatory mechanism of autophagy. MTOR inhibits the initiation of autophagy by inhibiting the Atg1 (mammalian ULK1). Various substances and stimuli can induce autophagy through the mTOR pathway, such as amino acids, energy, and oxidative stress. In chondrocytes, when mTOR is activated, it inhibits the expression of ULK1 and then affects the formation of ULK1, FIP200, and Atg13 complexes to inhibit the assembly of autophagic bodies. The function of beclin-1 in autophagy is regulated by Bcl-2, and Bcl-2 inhibits autophagy by combining and isolating beclin-1 under nutrient rich conditions. The induction of autophagy requires the dissociation of beclin-1 from Bcl-2. The formation of phagophore is driven by the beclin-1 associated class III PI3 Kinase with phosphatidylinositol3-phosphate-containing vesicles. The phagophore undergoes elongation and completion driven by two ubiquitin-related conjugation systems, the LC3-PE and Atg12-Atg5. Then, the autophagosome is fused with the lysosome. Finally, the substance degrades in the autolysosome and provides nutrients for the cells.

Figure 2

Chondrocyte homeostasis. The homeostasis of chondrocytes requires the extracellular matrix, oxidant defense mechanism, and autophagy. There is an inseparable relationship between the synthesis and metabolism of extracellular matrix and the activity of chondrocytes. Chondrocyte homeostasis plays an indispensable role in cell replication, differentiation, and development.