Characterising the effect of age and sex on post-transcriptional regulation in synovial joint tissues

Abstract

Age and sex are major risk factors for joint degeneration and disease susceptibility. While epigenetic and post-transcriptional mechanisms are known to be influenced by these factors, their effects on mRNA kinetics and configuration in musculoskeletal tissues remain poorly defined. To address this gap, we used an equine model to examine how age and sex impact mRNA stability in joint tissues. We measured global transcript half-life in primary chondrocytes from young and old female and young male horses using SLAM-seq. Polyadenylation patterns were additionally analysed in cartilage and synovium across age groups. Our findings demonstrated that age and sex exert distinct regulatory influences on post-transcriptional gene expression in joint tissues. Specifically, ageing alters polyadenylation site usage and transcript turnover in cartilage, even in absence of overt pathology, suggesting that molecular ageing may precede and predispose to joint degeneration. We also found that mean RNA half-life differed significantly between young females and males, with male chondrocytes showing greater transcript stability. This difference suggests that sex-specific regulatory mechanisms may influence RNA stability, which could contribute to differential susceptibility to joint degeneration. Together, these results point to age and sex as key drivers of post-transcriptional regulation with potential roles in shaping joint health trajectories. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/677035v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@99310borg.highwire.dtl.DTLVardef@162ee69org.highwire.dtl.DTLVardef@125108org.highwire.dtl.DTLVardef@860828_HPS_FORMAT_FIGEXP M_FIG C_FIG