Xiaoliang Yuan, Haiqing Liu, Linfu Li, Hai Liu, Jianqiong Yang, Weimei Shi, Yuan Feng, Hao Huang* and Longhuo Wu* Pages 1693 - 1704 ( 12 )
Endoplasmic reticulum (ER) has evolved an adaptive mechanism called unfolded protein response (UPR) at the initial stage to restore cellular homeostasis. The three ER transmembrane sensors, such as IRE1α, PERK, and ATF6, are the key factors to decide cell fates. They exhibit both advantageous and disadvantageous effects, depending on the micro-environmental state of cells. ER stress has been implicated in chondrocytes proliferation, differentiation, and hypertrophy through regulating transcriptional factors SOX9, Ihh, BMP-2, RUNX, and HIF1/2α. In addition, the chronic ER stress induced by the mutant proteins becomes the pathophysiology of chondrodysplasia. On the other hand, ER stress may induce chondrocytes apoptosis, leading to the degeneration of cartilage. eIF2α-CHOP and JNK activation are the remarkably apoptotic responses to ER stress, while XBP1s and Bip exhibit pro-survival effects. These factors might potentially become therapeutic targets for joint diseases management. This article reviews the pro-survival and pro-apoptotic effects of ER stress as well as their implications in cartilage and chondrocytes.
ER stress, UPR, chondrocytes, IRE1α-XBP1/IRE1α-RIDD, PERK- eIF2α, CHOP.
Department of Respiratory Medicine, the First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, College of Pharmacy, Gannan Medical University, Ganzhou 341000, College of Pharmacy, Gannan Medical University, Ganzhou 341000, College of Pharmacy, Gannan Medical University, Ganzhou 341000, Department of Clinical Research Center, the First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, College of Pharmacy, Gannan Medical University, Ganzhou 341000, Department of Biochemistry and Molecular Biology, Institute of Bioinformatics, University of Georgia, Athens 30602, GA, College of Pharmacy, Gannan Medical University, Ganzhou 341000, College of Pharmacy, Gannan Medical University, Ganzhou 341000