Cellular senescence is a biological state of a cell that triggers inflammation and gradually contributes to pathological conditions. Unlike programmed cell death, prolonged inhibition of cell division induces a metabolic state in senescent cells, in which they release pro-inflammatory factors that drive inflammation affecting the tissue microenvironment. Along with prolonged excessive mechanical stress, low-grade inflammation raised by senescent chondrocytes may contribute to articular cartilage defects, which are prevalent in ageing populations. Moreover, the use of chemotherapeutics used to improve cell differentiation can modulate senescence-associated effects in primary cells. We have inspected transcriptomic data of equine primary chondrocytes of the 4th passage expanded in a 2D culture system, stimulated with a low dose of trichostatin A (TSA) - a common histone deacetylase inhibitor (HDACi), to identify senescence-associated transcriptional response. We have identified downregulation of cell cycle and proliferation-related genes in TSA-stimulated chondrocytes. Cell cycle-related gene downregulation in equine chondrocytes, including those encoding CDK4 and pRb, without the involvement of the gene encoding p16INK4a, was observed. Upregulation of genes involved in oxidative phosphorylation and the proteasome pathway is consistent with a potentially protective effect of TSA on mitochondrial homeostasis. The unexpected transcriptional decline in FOXO signalling was characteristic of TSA-induced cartilage cells. Selective upregulation of immune-related genes in TSA-stimulated chondrocytes may reflect TSA-mediated modulation of the senescence-associated transcriptional response. The obtained results contribute to ongoing discussions regarding the use of HDACi as a therapeutic agent for the treatment of damaged articular cartilage.
