Vorinostat ameliorates IL‐1α‐induced reduction of type II collagen by inhibiting the expression of ELF3 in chondrocytes. Issue 9 (11th July 2021)

• Record Type: Journal Article
• Authors: Miao, Xudong; Wu, Yongping; Wang, Ping; Zhang, Qiang; Zhou, Chenhe; Yu, Xinning; Cao, Le
• Is Part Of: Journal of biochemical and molecular toxicology. Volume 35:Issue 9(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-11
• Subjects: chondrocytes -- ELF3 -- osteoarthritis -- type II collagen -- vorinostat; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Toxicology -- Periodicals; 574
• DOI: 10.1002/jbt.22844
• Languages: English
• ISSNs: 1095-6670

Abstract

Abstract: Osteoarthritis (OA) is a common joint disease that ultimately causes physical disability and imposes an economic burden on society. Cartilage destruction plays a key role in the development of OA. Vorinostat is an oral histone deacetylase (HDAC) inhibitor and has been used for the treatment of T‐cell lymphoma. Previous studies have reported the anti‐inflammatory effect of HDAC inhibitors in both in vivo and in vitro models. However, it is unknown whether vorinostat exerts a protective effect in OA. In this study, our results demonstrate that treatment with vorinostat prevents interleukin 1α (IL‐1α)‐induced reduction of type II collagen at both gene and protein levels. Treatment with vorinostat reduced the IL‐1α‐induced production of mitochondrial reactive oxygen species (ROS) in T/C‐28a2 cells. Additionally, vorinostat rescued the IL‐1α‐induced decrease in the expression of the collagen type II a1 ( Col2a1 ) gene and the expression of Sry‐related HMG box 9 (SOX‐9). Importantly, we found that vorinostat inhibited the expression of matrix metalloproteinase‐13 (MMP‐13), which is responsible for the degradation of type II collagen. Furthermore, vorinostat suppressed the expression of E74‐like factor 3 (ELF3), which is a key transcription factor that plays a pivotal role in the IL‐1α‐induced reduction of type II collagen. Also, the overexpression of ELF3 abolished the protective effects of vorinostat against IL‐1α‐induced loss of type 2 collagen by inhibiting the expression of SOX‐9 whilst increasing the expression of MMP‐13. In conclusion, our findings suggest that vorinostat might prevent cartilage destruction by rescuing the reduction of type II collagen, mediated by the suppression of ELF3.