IRE1 is an important central regulator of unfolded protein response (UPR) in the endoplasmic 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 endoribonuclease 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.

中文翻译：

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IRE1信号调节骨关节炎中的软骨细胞凋亡和死亡命运

IRE1 是内质网 (ER) 中未折叠蛋白反应 (UPR) 的重要中央调节因子，因为它能够根据压力感应调节细胞命运。当错误折叠的蛋白质在软骨细胞 ER 中积累时，IRE1 与 BIP/GRP78 分解并经历二聚体/寡聚化和反式自磷酸化。这两个过程是通过 IRE1 的酶活性介导的，以激活核糖核酸内切酶，并通过 XBP1 信使 RNA 的非常规剪接产生 XBP1。从而促进UPR靶基因的转录和细胞凋亡。软骨细胞中肌醇需要酶 1α (IRE1α) 的缺乏会下调促存活因子 XBP1S 和 Bcl-2，从而通过增加促凋亡因子 caspase-3、p-JNK 和 CHOP 来增强软骨细胞的凋亡。同时，IRE1α的激活增加了软骨细胞的活力并减少了细胞凋亡。然而，对 IRE1 反应和细胞死亡命运的理解仍然存在争议。这篇综述提供了关于 IRE1 在软骨细胞中的作用的最新数据，以及关于 IRE1 调节在软骨修复和骨关节炎治疗中的潜在功效的新见解。