Fig. 2

ER stress in the pathogenesis of OA. a Pathological changes in OA regulated by ER stress. b IRE1-mTORC1-PERK signaling pathway synergistically regulates autophagy and apoptosis in OA chondrocytes. Attenuation of IRE1 signaling activates mTORC1, converting protective autophagy to apoptosis. c Mechanisms through which ER stress accelerates OA progression in synovitis. A vicious cycle of HIF-1α-GLUT1-AGEs-HIF-1α may exist in the fibroblast-like synoviocyte of patients with diabetes-related OA, aggravating OA progression. d ER stress is involved in meniscal lesion to accelerate OA progression. Palmitate degrades ATG5 through the ERAD pathway to inhibit autophagy and promote meniscus cell apoptosis. AGEs advanced glycation end products, ATG5 autophagy-related 5, ER endoplasmic reticulum, ERAD ER-associated degradation, GLUT1 glucose transporter 1, HIF-1α hypoxia-inducible factor-1α, IRE1 inositol-requiring enzyme 1, mTORC1 mechanistic target of rapamycin complex 1, OA osteoarthritis, PERK protein kinase R-like ER kinase, RAGE receptor for AGEs