Duhuo Jisheng decoction inhibits endoplasmic reticulum stress in chondrocytes induced by tunicamycin through the downregulation of miR-34a.
Our previous study showed that Duhuo Jisheng decoction (DHJSD) inhibited chondrocyte apoptosis by the mitochondria-dependent signaling pathway. Endoplasmic reticulum (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.
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Fayuan
F
Liu
College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Xiaping
X
Weng
College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Pingdong
P
Lin
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Chunsong
C
Zheng
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Huifeng
H
Xu
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Xianxiang
X
Liu
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Hongzhi
H
Ye
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Xihai
X
Li
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D019902:Chondrocytes / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics; D010003:Osteoarthritis / Q000188:drug therapy / Q000235:genetics; D010654:Phenylbutyrates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014415:Tunicamycin / Q000494:pharmacology*
D004365:Drugs, Chinese Herbal; C560944:MIRN34 microRNA, rat; D035683:MicroRNAs; D010654:Phenylbutyrates; C000598415:duhuo jisheng; D014415:Tunicamycin; C075773:4-phenylbutyric acid