WISP1 Is Involved in the Pathogenesis of Kashin-Beck Disease via the Autophagy Pathway.
WISP1 Is Involved in the Pathogenesis of Kashin-Beck Disease via the Autophagy Pathway.
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WISP1通过自噬途径参与大骨节病的发病机制
DOI：
10.3390/ijms242216037
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发表时间：
2023-11-07
影响因子：
5.6
通讯作者：
Zhang, Feng
中科院分区：
文献类型：
--
作者：
Li, Ping;Cheng, Bolun;Yao, Yao;Yu, Wenxing;Liu, Li;Cheng, Shiqiang;Zhang, Lu;Ma, Mei;Qi, Xin;Liang, Chujun;Chu, Xiaomeng;Ye, Jing;Sun, Shiquan;Jia, Yumeng;Guo, Xiong;Wen, Yan;Zhang, Feng
目的：大骨节病（KBD）是我国一种地方性慢性骨软骨病。本研究旨在探讨Wnt诱导的信号通路蛋白1（WISP 1）在大骨节病发病中的功能相关性及其可能机制。设计：收集大骨节病和对照组软骨标本，进行组织切片观察和软骨细胞原代培养。首先，在光镜和电镜下进行形态学和组织病理学观察。采用qRT-PCR、Western blot和免疫组织化学方法检测大骨节病软骨细胞和对照软骨细胞中WISP 1的表达水平以及与自噬途径和细胞外基质（ECM）合成相关的分子标志物。此外，应用慢病毒转染技术，建立了基于大骨节病软骨细胞的WISP 1基因敲除细胞模型。使用人重组WISP 1（rWISP 1）对C28/I2人软骨细胞系进行体外干预实验。结果：大骨节病软骨细胞内出现自溶酶体。WISP 1在大骨节病软骨细胞中的表达明显增强。此外，T-2毒素，大骨节病发病的危险因素，可以上调WISP 1在C28/I2的表达。自噬标志物ATG 4C和LC 3 II在低浓度T-2毒素处理后上调，在高浓度处理后下调。敲低KBD软骨细胞中WISP 1表达后，MAP 1 LC 3B减少，而ATG 4C和COL 2A 1增加。rWISP 1蛋白处理C28/I2软骨细胞后，ATG 4C和LC 3 II的表达先上调后下调。结论：WISP 1可能通过自噬在大骨节病的发病机制中发挥作用。
Objective: Kashin-Beck disease (KBD) is a kind of endemic and chronic osteochondropathy in China. This study aims to explore the functional relevance and potential mechanism of Wnt-inducible signaling pathway protein 1 (WISP1) in the pathogenesis of KBD. Design: KBD and control cartilage specimens were collected for tissue section observation and primary chondrocyte culture. Firstly, the morphological and histopathological observations were made under a light and electron microscope. Then, the expression levels of WISP1 as well as molecular markers related to the autophagy pathway and extracellular matrix (ECM) synthesis were detected in KBD and control chondrocytes by qRT-PCR, Western blot, and immunohistochemistry. Furthermore, the lentiviral transfection technique was applied to make a WISP1 knockdown cell model based on KBD chondrocytes. In vitro intervention experiments were conducted on the C28/I2 human chondrocyte cell line using human recombinant WISP1 (rWISP1). Results: The results showed that the autolysosome appeared in the KBD chondrocytes. The expression of WISP1 was significantly higher in KBD chondrocytes. Additionally, T-2 toxin, a risk factor for KBD onset, could up-regulate the expression of WISP1 in C28/I2. The autophagy markers ATG4C and LC3II were upregulated after the low-concentration treatment of T-2 toxin and downregulated after the high-concentration treatment. After knocking down WISP1 expression in KBD chondrocytes, MAP1LC3B decreased while ATG4C and COL2A1 increased. Moreover, the rWISP1 protein treatment in C28/I2 chondrocytes could upregulate the expression of ATG4C and LC3II at the beginning and downregulate them then. Conclusions: Our study suggested that WISP1 might play a role in the pathogenesis of KBD through autophagy.
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影响因子：
5.6
作者：
Pascarelli NA;Collodel G;Moretti E;Cheleschi S;Fioravanti A
通讯作者：
Fioravanti A
DOI：
10.1016/j.biocel.2015.03.007
发表时间：
2015-05-01
影响因子：
4
作者：
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通讯作者：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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