Dynamic interplay between connective tissues and the surrounding environment during aging

Diekman, Brian O.

doi:10.1080/03008207.2020.1682282

Cited by 3 publications

(1 citation statement)

References 11 publications

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“…SOX‐9 is a key transcription factor in cartilage tissue; its expression is important for chondrogenesis and chondrocyte survival. [ 38 ] A recent study showed that blockade of SOX‐9 with siRNA reduced the expression of type II collagen ( Col2a1 ) at both mRNA and protein levels, [ 39 ] while IL‐1β stimulation inhibits COL2A1 gene expression by suppressing SOX‐9 promoter activity in chondrocytes. [ 40 ] In the current study, we found a significant decrease in SOX‐9 induced by IL‐1α, resulting in the suppression of type II collagen at the gene level, which was rescued by the two doses of vorinostat, in a dose‐dependent manner.…”

Section: Discussionmentioning

confidence: 99%

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

Miao

Wang

et al. 2021

J Biochem & Molecular Tox

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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.

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Section: Discussionmentioning

confidence: 99%