衣霉素诱导的内质网应激影响软骨细胞的活力和自噬活性。,Journal of Clinical Laboratory Analysis

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衣霉素诱导的内质网应激影响软骨细胞的活力和自噬活性。
Journal of Clinical Laboratory Analysis ( IF 2.6 ) Pub Date : 2020-06-26 , DOI: 10.1002/jcla.23437
Hao Wu ₁ , Zhichao Meng ₁ , Yang Jiao ₁ , Yali Ren ₂ , Xin Yang ₁ , Heng Liu ₁ , Rui Wang ₁ , Yunpeng Cui ₁ , Liping Pan ₁ , Yongping Cao ₁

Affiliation

骨关节炎 (OA) 归因于关节软骨内软骨细胞的减少，研究表明内质网 (ER) 应激和自噬在软骨细胞的存活中起重要作用。然而，内质网应激与软骨细胞自噬之间的关系仍不清楚。在这项研究中，我们研究了内质网应激下软骨细胞凋亡和自噬活性的变化。用衣霉素处理后，软骨细胞的凋亡率增加。蛋白质印迹分析显示未折叠蛋白反应 (UPR) 相关蛋白的水平增加，随后轻链 3B-II (LC3B-II) 和 Beclin-1 的表达升高。超微结构研究表明，在衣霉素处理下形成了大量的前自噬体结构或自噬体。然而，siRNA抑制GRP78后，软骨细胞的自噬活性受到显着抑制。暴露于衣霉素后，用 3-甲基腺嘌呤预处理的软骨细胞的凋亡率远高于正常软骨细胞。我们的研究表明，衣霉素诱导的持续 UPR 表达导致软骨细胞凋亡和自噬与 GRP78 结合的激活。阻断自噬加速了内质网应激诱导的细胞凋亡，证实了自噬在软骨细胞稳态中的保护作用。这些发现促进了我们对软骨细胞凋亡的理解，并为预防软骨细胞凋亡提供了潜在的分子靶点。暴露于衣霉素后，用 3-甲基腺嘌呤预处理的软骨细胞的凋亡率远高于正常软骨细胞。我们的研究表明，衣霉素诱导的持续 UPR 表达导致软骨细胞凋亡和自噬与 GRP78 结合的激活。阻断自噬加速了内质网应激诱导的细胞凋亡，证实了自噬在软骨细胞稳态中的保护作用。这些发现促进了我们对软骨细胞凋亡的理解，并为预防软骨细胞凋亡提供了潜在的分子靶点。暴露于衣霉素后，用 3-甲基腺嘌呤预处理的软骨细胞的凋亡率远高于正常软骨细胞。我们的研究表明，衣霉素诱导的持续 UPR 表达导致软骨细胞凋亡和自噬与 GRP78 结合的激活。阻断自噬加速了内质网应激诱导的细胞凋亡，证实了自噬在软骨细胞稳态中的保护作用。这些发现促进了我们对软骨细胞凋亡的理解，并为预防软骨细胞凋亡提供了潜在的分子靶点。我们的研究表明，衣霉素诱导的持续 UPR 表达导致软骨细胞凋亡和自噬与 GRP78 结合的激活。阻断自噬加速了内质网应激诱导的细胞凋亡，证实了自噬在软骨细胞稳态中的保护作用。这些发现促进了我们对软骨细胞凋亡的理解，并为预防软骨细胞凋亡提供了潜在的分子靶点。我们的研究表明，衣霉素诱导的持续 UPR 表达导致软骨细胞凋亡和自噬与 GRP78 结合的激活。阻断自噬加速了内质网应激诱导的细胞凋亡，证实了自噬在软骨细胞稳态中的保护作用。这些发现促进了我们对软骨细胞凋亡的理解，并为预防软骨细胞凋亡提供了潜在的分子靶点。

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

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.

更新日期：2020-06-26

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