The endoplasmic reticulum stress induced by tunicamycin affects the viability and autophagy activity of chondrocytes.

Osteoarthritis (OA) is attributed to a reduction in chondrocytes within joint cartilage, and research has shown that endoplasmic reticulum (ER) stress and autophagy play important roles in the survival of chondrocytes. However, the relationship between ER stress and autophagy in chondrocytes remains unclear. In this study, we investigated the changes in apoptotic and autophagic activity in chondrocytes under ER stress. Following treatment with tunicamycin, the rate of apoptosis among chondrocytes increased. Western blot analysis showed the levels of unfolded protein response (UPR) related proteins increased, followed by elevated expression of light chain 3B-II (LC3B-II) and Beclin-1. An ultrastructural investigation showed that a large number of pre-autophagosomal structures or autophagosomes formed under tunicamycin treatment. However, the autophagy activity was significantly inhibited in chondrocytes after suppression of GRP78 by siRNA. The apoptosis ratio of chondrocytes pre-treated with 3-methyladenine was much higher than that of normal chondrocytes after exposure to tunicamycin. Our study revealed that the tunicamycin-induced persistent UPR expression led to apoptosis of chondrocytes and activation of autophagy incorporation with GRP78. Blocking autophagy accelerated the apoptosis induced by ER stress, which confirmed the protective function of autophagy in the homeostasis of chondrocytes. These findings advance our understanding of chondrocyte apoptosis and provide potential molecular targets for preventing apoptotic death of chondrocytes.