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.

中文翻译：

---

Vorinostat 通过抑制软骨细胞中 ELF3 的表达改善 IL-1α 诱导的 II 型胶原减少

骨关节炎（OA）是一种常见的关节疾病，最终导致身体残疾并给社会带来经济负担。软骨破坏在 OA 的发展中起着关键作用。Vorinostat 是一种口服组蛋白脱乙酰酶 (HDAC) 抑制剂，已用于治疗 T 细胞淋巴瘤。先前的研究已经报道了 HDAC 抑制剂在体内和体外模型中的抗炎作用。然而，伏立诺他是否对 OA 具有保护作用尚不清楚。在这项研究中，我们的结果表明，伏立诺他治疗可以防止白细胞介素 1α (IL-1α) 诱导的基因和蛋白质水平上的 II 型胶原蛋白减少。伏立诺他治疗减少了 T/C-28a2 细胞中 IL-1α 诱导的线粒体活性氧 (ROS) 的产生。此外，伏立诺他还挽救了 IL-1α 诱导的 II 型胶原蛋白 a1 ( Col2a1 ) 基因表达和 Sry 相关 HMG box 9 (SOX-9) 表达的降低。重要的是，我们发现伏立诺他抑制基质金属蛋白酶-13 (MMP-13) 的表达，而基质金属蛋白酶-13 负责 II 型胶原蛋白的降解。此外，伏立诺他抑制了 E74 样因子 3 (ELF3) 的表达，ELF3 是一种关键转录因子，在 IL-1α 诱导的 II 型胶原蛋白减少中发挥着关键作用。此外，ELF3 的过度表达通过抑制 SOX-9 的表达同时增加 MMP-13 的表达，消除了伏立诺他对 IL-1α 诱导的 2 型胶原丢失的保护作用。总之，我们的研究结果表明，伏立诺他可能通过挽救由抑制 ELF3 介导的 II 型胶原蛋白的减少来防止软骨破坏。