4-Phenylbutyric acid presents therapeutic effect on osteoarthritis via inhibiting cell apoptosis and inflammatory response induced by endoplasmic reticulum stress
Autor: | Wenjie Zheng, Yue Zhenshuang, Tang Yanghua, Xiong Zhenfei, Hong-fei Shen, Zhongqing Hu, Lin-ru Zeng |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
TUNEL assay 030102 biochemistry & molecular biology Chemistry Process Chemistry and Technology Endoplasmic reticulum medicine.medical_treatment Biomedical Engineering Bioengineering General Medicine CHOP Matrix metalloproteinase Applied Microbiology and Biotechnology 03 medical and health sciences 030104 developmental biology Cytokine Downregulation and upregulation Apoptosis Drug Discovery Unfolded protein response medicine Cancer research Molecular Medicine Biotechnology |
Zdroj: | Biotechnology and Applied Biochemistry. 65:540-546 |
ISSN: | 0885-4513 |
DOI: | 10.1002/bab.1642 |
Popis: | Osteoarthritis (OA) is a common bone and joint disease with a wild range of risk factors, which is associated with endoplasmic reticulum (ER) stress. The aim of our study was to discuss the possible mechanism of ER stress associated with OA in vivo and explore novel therapeutic method against OA. OA-induced damages in cartilage tissues were evaluated by HE, Safranin O/fast green, and TUNEL staining. The inflammatory factors concentration and the expression of FAP, MMP2, MMP9, Bax, Bcl-2, CHOP, and GRP78 were evaluated by ELISA, real-time PCR, and Western blot analyses. As results, 4-phenylbutyric acid (4-PBA)-treated OA cartilage tissues presented alleviated tissue damage with less apoptotic cells and cytokine production in comparison with advanced-OA tissues. Downregulation of Bax/Bcl-2, CHOP, GRP78, inflammatory factors, and reactive oxygen species generation, and the increase of MMP level detected after 4-PBA treatment indicated an inhibitory effect of 4-PBA on cell apoptosis, inflammatory response, and ER stress in OA. In conclusion, we indicate that ER stress causes cell apoptosis and inflammatory response, resulting in the tissue damage within OA. At the same time, 4-PBA exhibited protective effect on cartilage cells against OA through the inhibition of ER stress. |
Databáze: | OpenAIRE |
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