IRE1 signaling regulates chondrocyte apoptosis and death fate in the osteoarthritis

Rongxiang Huang; Zhang Hui; Sun WeiDuan LiWencui LiWang DapingMurad Alahdal

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IRE1 signaling regulates chondrocyte apoptosis and death fate in the osteoarthritis

机译：IRE1信号调节软骨细胞凋亡骨关节炎死亡的命运

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IRE1 is an important central regulator of unfolded protein response (UPR) in the en-doplasmic reticulum (ER) because of its ability to regulate cell fate as a function of stress sensing. When misfolded proteins accumulated in chondrocytes ER, IRE1 disintegrates with BIP/GRP78 and undergoes dimer/oligomerization and transautophosphorylation. These two processes are mediated through an enzyme activity of IRE1 to activate en-doribonuclease and generates XBP1 by unconventional splicing of XBP1 messenger RNA. Thereby promoting the transcription of UPR target genes and apoptosis. The deficiency of inositol-requiring enzyme 1α (IRE1α) in chondrocytes downregulates prosurvival factors XBP1S and Bcl-2, which enhances the apoptosis of chondrocytes through increasing proapoptotic factors caspase-3, p-JNK, and CHOP. Meanwhile, the activation of IRE1α increases chondrocyte viability and reduces cell apoptosis. However, the understanding of IRE1 responses and cell death fate remains controversial. This review provides updated data about the role IRE1 plays in chondrocytes and new insights about the potential efficacy of IRE1 regulation in cartilage repair and osteoarthritis treatment.

机译：IRE1是一个重要的中央监管机构展开en-doplasmic蛋白质反应(UPR)网(ER)由于其调节的能力细胞命运的压力传感。错误折叠的蛋白质积累在软骨细胞呃,IRE1毕普/ GRP78和分解经历了二聚体/寡聚化和transautophosphorylation。通过酶活性的IRE1介导激活en-doribonuclease并生成XBP1的非常规XBP1信使RNA剪接。从而促进转录的UPR的目标基因和细胞凋亡。inositol-requiring酶1α(IRE1α)软骨细胞会使prosurvival因素XBP1S和bcl - 2,这增强了细胞凋亡软骨细胞通过增加proapoptotic因素caspase-3, p-JNK,切。软骨细胞的激活IRE1α增加生存能力,减少细胞凋亡。的理解IRE1反应和细胞死亡的命运仍然是有争议的。提供更新的数据IRE1扮演的角色在软骨细胞和新见解IRE1监管的潜在功效骨关节炎软骨修复和治疗。

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《Journal of cellular physiology.》 |2022年第1期|118-127|共10页
作者
Rongxiang Huang; Zhang Hui; Sun WeiDuan LiWencui LiWang DapingMurad Alahdal;
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作者单位

Shenzhen Key Laboratory of Tissue Engineering, Shenzhen Laboratory of Digital Orthopedic;

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正文语种英语
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关键词
ERN1 gene; Chondrocyte; OsteoarthritisApoptosisErbiumXBP1 gene;

机译：ERN1基因;软骨细胞;OsteoarthritisApoptosisErbiu;

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IRE1 signaling regulates chondrocyte apoptosis and death fate in the osteoarthritis

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