PMID- 26497741 OWN - NLM STAT- MEDLINE DCOM- 20160912 LR - 20220113 IS - 1791-244X (Electronic) IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 36 IP - 6 DP - 2015 Dec TI - Bushen Zhuangjin decoction inhibits TM-induced chondrocyte apoptosis mediated by endoplasmic reticulum stress. PG - 1519-28 LID - 10.3892/ijmm.2015.2387 [doi] AB - Chondrocyte apoptosis triggered by endoplasmic reticulum (ER) stress plays a vital role in the pathogenesis of osteoarthritis (OA). Bushen Zhuangjin decoction (BZD) has been widely used in the treatment of OA. However, the cellular and molecular mechanisms responsible for the inhibitory effects of BZD on chondrocyte apoptosis remain to be elucidated. In the present study, we investigated the effects of BZD on ER stress-induced chondrocyte apoptosis using a chondrocyte in vitro model of OA. Chondrocytes obtained from the articular cartilage of the knee joints of Sprague Dawley (SD) rats were detected by immunohistochemical staining for type Ⅱ collagen. The ER stress-mediated apoptosis of tunicamycin (TM)‑stimulated chondrocytes was detected using 4-phenylbutyric acid (4‑PBA). We found that 4‑PBA inhibited TM-induced chondrocyte apoptosis, which confirmed the successful induction of chondrocyte apoptosis. BZD enhanced the viability of the TM-stimulated chondrocytes in a dose- and time-dependent manner, as shown by MTT assay. The apoptotic rate and the loss of mitochondrial membrane potential (DeltaPsim) of the TM-stimulated chondrocytes treated with BZD was markedly decreased compared with those of chondrocytes not treated with BZD, as shown by 4',6-diamidino-2-phenylindole (DAPI) staining, Annexin V-FITC binding assay and JC-1 assay. To further elucidate the mechanisms responsible for the inhibitory effects of BZD on TM‑induced chondrocyte apoptosis mediated by ER stress, the mRNA and protein expression levels of binding immunoglobulin protein (Bip), X‑box binding protein 1 (Xbp1), activating transcription factor 4 (Atf4), C/EBP‑homologous protein (Chop), caspase‑9, caspase-3, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were measured by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. In the TM-stimulated chondrocytes treated with BZD, the mRNA and protein expression levels of Bip, Atf4, Chop, caspase-9, caspase-3 and Bax were significantly decreased, whereas the mRNA and protein expression levels of Xbp1 and Bcl-2 were significantly increased compared with the TM‑stimulated chondrocytes not treated with BZD. Additionally, all our findings demonstrated that there was no significant difference between the TM‑stimulated chondrocytes treated with BZD and those treated with 4‑PBA. Taken together, our results indicate that BZD inhibits TM‑induced chondrocyte apoptosis mediated by ER stress. Thus, BZD may be a potential therapeutic agent for use in the treatment of OA. FAU - Lin, Pingdong AU - Lin P AD - College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China. FAU - Weng, Xiaping AU - Weng X AD - College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China. FAU - Liu, Fayuan AU - Liu F AD - Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China. FAU - Ma, Yuhuan AU - Ma Y AD - College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China. FAU - Chen, Houhuang AU - Chen H AD - Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China. FAU - Shao, Xiang AU - Shao X AD - Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China. FAU - Zheng, Wenwei AU - Zheng W AD - Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China. FAU - Liu, Xianxiang AU - Liu X AD - Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China. FAU - Ye, Hongzhi AU - Ye H AD - College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China. FAU - Li, Xihai AU - Li X AD - Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151022 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Bax protein, rat) RN - 0 (DNA-Binding Proteins) RN - 0 (Ddit3 protein, rat) RN - 0 (Drugs, Chinese Herbal) RN - 0 (GRP78 protein, rat) RN - 0 (Heat-Shock Proteins) RN - 0 (Phenylbutyrates) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Regulatory Factor X Transcription Factors) RN - 0 (Transcription Factors) RN - 0 (X-Box Binding Protein 1) RN - 0 (Xbp1 protein, rat) RN - 0 (bcl-2-Associated X Protein) RN - 0 (bushen zhuangjin) RN - 11089-65-9 (Tunicamycin) RN - 147336-12-7 (Transcription Factor CHOP) RN - 7WY7YBI87E (4-phenylbutyric acid) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspase 9) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Blotting, Western MH - Caspase 3/genetics/metabolism MH - Caspase 9/genetics/metabolism MH - Cells, Cultured MH - Chondrocytes/cytology/*drug effects/metabolism MH - DNA-Binding Proteins/genetics/metabolism MH - Drugs, Chinese Herbal/*pharmacology MH - Endoplasmic Reticulum Stress/*drug effects MH - Gene Expression/drug effects MH - Heat-Shock Proteins/genetics/metabolism MH - Membrane Potential, Mitochondrial/drug effects MH - Phenylbutyrates/pharmacology MH - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism MH - Rats, Sprague-Dawley MH - Regulatory Factor X Transcription Factors MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transcription Factor CHOP/genetics/metabolism MH - Transcription Factors/genetics/metabolism MH - Tunicamycin/*pharmacology MH - X-Box Binding Protein 1 MH - bcl-2-Associated X Protein/genetics/metabolism PMC - PMC4678159 EDAT- 2015/10/27 06:00 MHDA- 2016/09/13 06:00 PMCR- 2015/10/22 CRDT- 2015/10/27 06:00 PHST- 2015/03/22 00:00 [received] PHST- 2015/10/08 00:00 [accepted] PHST- 2015/10/27 06:00 [entrez] PHST- 2015/10/27 06:00 [pubmed] PHST- 2016/09/13 06:00 [medline] PHST- 2015/10/22 00:00 [pmc-release] AID - ijmm-36-06-1519 [pii] AID - 10.3892/ijmm.2015.2387 [doi] PST - ppublish SO - Int J Mol Med. 2015 Dec;36(6):1519-28. doi: 10.3892/ijmm.2015.2387. Epub 2015 Oct 22.