Role of endoplasmic reticulum stress pathway in hydrostatic pressure-induced apoptosis in rat mandibular condylar chondrocytes
Role of endoplasmic reticulum stress pathway in hydrostatic pressure-induced apoptosis in rat mandibular condylar chondrocytes
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内质网应激通路在静水压诱导大鼠下颌髁突软骨细胞凋亡中的作用
DOI：
10.1007/s11010-016-2933-5
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发表时间：
2017-02
影响因子：
4.3
通讯作者：
Wu HL
中科院分区：
文献类型：
--
作者：
Xu Ting;Xu Ting;Xu Gaoli;Gu Zhiyuan;Wu Huiling;Gu ZY;Wu HL
过度的机械负荷会导致软骨细胞凋亡和不可逆的软骨退化，但其潜在的分子机制尚不清楚。本研究的目的是探讨内质网（ER）应激途径在静水压（HP）诱导的大鼠下颌髁突软骨细胞凋亡中的可能作用。从大鼠下颌髁软骨中分离软骨细胞并进行 HP。通过 Cell Counting Kit-8 和流式细胞术测定细胞活力和凋亡。通过实时定量PCR和蛋白质印迹分析检测内质网应激相关分子的表达。此外，还通过蛋白质印迹评估了凋亡相关蛋白（bax、bcl-2 和 cleaved-caspase-3）的表达。为了探索 ER 应激功能，在暴露于 HP 之前用 salubrinal 预处理软骨细胞。通过实时 PCR 评估 II 型胶原蛋白、聚集蛋白聚糖、MMP-13 和 ADAMTS-5 的表达。结果表明，HP 以幅度和时间依赖性方式降低细胞活力。 HP 通过增加软骨细胞中 GRP78、CHOP、caspase-12、PERK 和 peIF2α 的表达来诱导 ER 应激通路的激活。此外，随着应激时间的延长，bax和cleaved-caspase-3的表达增加，而bcl-2的表达减少。此外，salubrinal 抑制 HP 诱导的细胞凋亡，上调 II 型胶原和聚集蛋白聚糖 mRNA 表达，并下调 MMP-13 和 ADAMTS-5 mRNA 表达以响应 HP。这些结果表明HP通过ER应激介导的细胞凋亡途径诱导下颌髁突软骨细胞凋亡。 salubrinal 抑制 ER 应激可防止软骨细胞发生 HP 诱导的细胞凋亡和基质降解。
Excessive mechanical loads induce chondrocyte apoptosis and irreversible cartilage degeneration, but the underlying molecular mechanism is poorly understood. The aim of this study was to investigate the possible role of endoplasmic reticulum (ER) stress pathway in hydrostatic pressure (HP)-induced apoptosis in rat mandibular condylar chondrocytes. Chondrocytes were isolated from rat mandibular condylar cartilage and subjected to HP. Cell viability and apoptosis were assessed by Cell Counting Kit-8 and flow cytometry assay. Expression of ER stress-associated molecules was detected by quantitative real-time PCR and western blot analysis. In addition, expression of apoptosis-related proteins (bax, bcl-2, and cleaved-caspase-3) was assessed by western blot. To explore ER stress function, chondrocytes were pretreated with salubrinal before exposure to HP. Expression of type II collagen, aggrecan, MMP-13, and ADAMTS-5 was evaluated by real-time PCR. The results indicated that HP reduced cell viability in a magnitude- and time-dependent manner. HP-induced activation of ER stress pathway by increasing expression of GRP78, CHOP, caspase-12, PERK, and peIF2α in chondrocytes. Moreover, the expression of bax and cleaved-caspase-3 was increased, while the expression of bcl-2 was decreased in response to HP as the stress time prolonged. In addition, salubrinal suppressed HP-induced apoptosis, upregulated type II collagen and aggrecan mRNA expression, and downregulated MMP-13 and ADAMTS-5 mRNA expression in response to HP. These results demonstrate that HP induces apoptosis in mandibular condylar chondrocytes through ER stress-mediated apoptotic pathway. Suppression of ER stress by salubrinal prevents chondrocytes from undergoing apoptosis and matrix degradation induced by HP.
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影响因子：
21.3
作者：
Tabas, Ira;Ron, David
通讯作者：
Ron, David
影响因子：
3.2
作者：
Nugent, Ashleigh E.;Speicher, Danielle M.;Horton, Walter E., Jr.
通讯作者：
Horton, Walter E., Jr.
影响因子：
4.8
作者：
Morishima, N;Nakanishi, K;Yasuhiko, Y
通讯作者：
Yasuhiko, Y
DOI：
10.1016/b978-0-08-102723-3.00239-0
发表时间：
2021
期刊：
Reference Module in Biomedical Sciences
影响因子：
--
作者：
Stephen E. Epstein;C. Siegall;Sadatoshi Biro;Yao Fu;David FitzGerald;Ira Pastan
通讯作者：
Stephen E. Epstein;C. Siegall;Sadatoshi Biro;Yao Fu;David FitzGerald;Ira Pastan
Salubrinal在各种压缩机械刺激下对颞下颌关节软骨和软骨下骨的保护作用
影响因子：
3.7
作者：
Wen J;Jiang Y;Zhang C;Chen S;Li H
通讯作者：
Li H