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

Abstract

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.

Resveratrol Attenuates the Mitochondrial RNA-Mediated Cellular Response to Immunogenic Stress

“…We chose OA and TN as two representative stressors that target mitochondria or ER, respectively. OA is an inhibitor of ATP synthase in the electron transfer system often used to induce mitochondrial dysfunction [ 10 , 46 , 47 ], and TN is known to induce ER stress by promoting the accumulation of unfolded proteins in the ER lumen [ 48 , 49 , 50 ]. With these stressors, we analyzed first whether they could induce the expression of mtRNAs, and then whether RES could counter the downstream effects of these stressors.…”

Molecular and Cellular Effects of Chemical Chaperone—TUDCA on ER-Stressed NHAC-kn Human Articular Chondrocytes Cultured in Normoxic and Hypoxic Conditions

“…In this respect, we performed our experiments in both normoxic (21% O 2 ) and hypoxic (1% O 2 ) conditions, first evaluating the expression of HIF1α in treated chondrocytes ( Figure 2 A–D). Although 20% of oxygen is unachievable in chondrocyte cells, and only 5–8% of O 2 is normally present in these cells, using ≈20% O 2 is commonly accepted model of normoxic conditions in plethora of different cell types [ 53 ]. Thus, it has also been translated into chondrocyte-based in vitro research as standard cell culture condition, called “normoxia’’ [ 54 , 55 ].…”

Endoplasmic Reticulum Stress in Osteoarthritis: A Novel Perspective on the Pathogenesis and Treatment

“…Excessive and prolonged ER stress can lead to chondrocyte apoptosis, while mild ER stress can activate autophagy via the GRP78 pathway and protect chondrocytes from apoptosis [4]. However, the complicated crosstalk among ER stress, autophagy, and apoptosis has not been completely elucidated.…”