Vorinostat ameliorates IL‐1α‐induced reduction of type II collagen by inhibiting the expression of ELF3 in chondrocytes

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.

Single-cell RNA sequence presents atlas analysis for chondrocytes in the talus and reveals the potential mechanism in coping with mechanical stress

“…BHELHE40 is reported to be a target of HIF-1 and also participates in chondrocyte development ( Shen et al, 1997 ; Miyazaki et al, 2002 ; Shen et al, 2002 ), which is in accordance with the possible function of MirCs. ELF3 is demonstrated to be a harmful gene in preventing OA progression and also participates in dysregulation of COL2A1 , which corresponds to the potential role of SpCs ( Otero et al, 2017 ; Miao et al, 2021 ). The roles of CEBPG and CHURC1 in chondrocytes required further exploration.…”

Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect

“…An imbalance in the anabolism and catabolism of chondrocytes contributes to reduced force absorption ( Chen et al, 2021 ; Tao et al, 2021 ). Collagen II, as one of the most important indexes of anabolism, is the main component of cartilage protein and provides a network structure that can obtain stability from other collagen types and non-collagen proteins and impart tensile strength to articular cartilage ( Miao et al, 2021 ). In addition, aggrecan, another major anabolic indicator and cartilage protein, can incorporate water molecules into cartilage to provide compressive strength ( Buckwalter et al, 2005 ; Pearle et al, 2005 ).…”