Duhuo Jisheng decoction inhibits endoplasmic reticulum stress in chondrocytes induced by tunicamycin through the downregulation of miR-34a

被引:42
作者
Liu, Fayuan [1 ,4 ]
Weng, Xiaping [2 ]
Lin, Pingdong [2 ]
Zheng, Chunsong [1 ,3 ]
Xu, Huifeng [1 ,3 ]
Liu, Xianxiang [1 ]
Ye, Hongzhi [1 ]
Li, Xihai [1 ]
机构
[1] Fujian Univ Tradit Chinese Med, Acad Integrat Med, Fuzhou 350122, Fujian, Peoples R China
[2] Fujian Univ Tradit Chinese Med, Coll Pharm, Fuzhou 350122, Fujian, Peoples R China
[3] Fujian Univ Tradit Chinese Med, Fujian Key Lab Integrat Med Geriatr, Fuzhou 350122, Fujian, Peoples R China
[4] Putian Xiuyuqu Hosp, Putian 351146, Fujian, Peoples R China
基金
中国国家自然科学基金;
关键词
Duhuo Jisheng decoction; chondrocyte; endoplasmic reticulum stress; apoptosis; miR-34a; UNFOLDED PROTEIN RESPONSE; ER STRESS; INDUCED APOPTOSIS; SIGNALING PATHWAY; CARTILAGE MATRIX; IMMUNE-SYSTEM; CELL-DEATH; OSTEOARTHRITIS; MICRORNAS; PROLIFERATION;
D O I
10.3892/ijmm.2015.2331
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
100103 [病原生物学]; 100218 [急诊医学];
摘要
Our previous study showed that Duhuo Jisheng decoction (DHJSD) inhibited chondrocyte apoptosis by the mitochondria-dependent signaling pathway. Endoplasmic retieulum (ER) stress is upstream of the mitochondria-dependent signaling pathway and has been shown to promote chondrocyte apoptosis that occurs in osteoarthritis (OA). The present study aimed to evaluate whether DHJSD inhibits the chondrocyte apoptosis by regulating ER stress. DHJSD enhanced the viability of tunicamycin (TM)-exposed chondrocytes, a model of ER stress-induced apoptosis, in a dose- and time-dependent manner, as shown by MTT assay. The present results showed that DHJSD and sodium 4-phenylbutyrate (PBA), an ER stress inhibitor, reduced TM-induced chondrocyte apoptosis by 4',6-diamidino-2-phenylindole staining. To gain insight into the mechanisms of DHJSD that are responsible for enhancing the viability and inhibiting TM-induced chondrocyte apoptosis, the associated mRNA expressions and protein levels were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis, respectively. The results showed that the expression levels of Xbp1, Xbp1s and Bcl-2 were increased, and the expression levels of Bip, Atf4, Chop, Bax, caspase-9 and -3 were decreased in the TM-exposed chondrocytes treated with DHJSD or PBA compared with that in the TM-exposed chondrocytes. To identify the possible mechanisms, the expression of miR-34a was examined by the TaqMan microRNA assay, and was downregulated in the TM-exposed chondrocytes treated with DHJSD or PBA compared with that in the TM-exposed chondrocytes. DHJSD inhibits ER stress in chondrocytes induced by exposure to TM by downregulating miR-34a, suggesting that DHJSD may be a potential therapeutic agent for OA.
引用
收藏
页码:1311 / 1318
页数:8
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