Bushen Zhuangjin decoction inhibits TM-induced chondrocyte apoptosis mediated by endoplasmic reticulum stress.
Int J Mol Med
; 36(6): 1519-28, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26497741
ABSTRACT
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 â
¡ collagen. The ER stress-mediated apoptosis of tunicamycin (TM)stimulated chondrocytes was detected using 4-phenylbutyric acid (4PBA). We found that 4PBA 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 (ΔΨm) 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 TMinduced chondrocyte apoptosis mediated by ER stress, the mRNA and protein expression levels of binding immunoglobulin protein (Bip), Xbox binding protein 1 (Xbp1), activating transcription factor 4 (Atf4), C/EBPhomologous protein (Chop), caspase9, 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 TMstimulated chondrocytes not treated with BZD. Additionally, all our findings demonstrated that there was no significant difference between the TMstimulated chondrocytes treated with BZD and those treated with 4PBA. Taken together, our results indicate that BZD inhibits TMinduced chondrocyte apoptosis mediated by ER stress. Thus, BZD may be a potential therapeutic agent for use in the treatment of OA.
Texto completo:
1
Base de dados:
MEDLINE
Medicinas Tradicionais:
Medicinas_tradicionales_de_asia
/
Medicina_china
Assunto principal:
Medicamentos de Ervas Chinesas
/
Tunicamicina
/
Apoptose
/
Condrócitos
/
Estresse do Retículo Endoplasmático
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Int J Mol Med
Ano de publicação:
2015
Tipo de documento:
Article