Epigenetic regulation and mechanobiological adaptation in tenocytes during maturation

Tendons are essential for musculoskeletal function, facilitating movement by transmitting forces from muscles to bones. However, aging alters the tendon microenvironment, disrupting the delicate interactions between tenocytes and the extracellular matrix (ECM), contributing to tissue degeneration. While prior studies have characterized the mechanical and structural changes in tendons during maturation, the epigenetic regulation of tenocyte function during aging remains poorly understood. Here, we investigate age-dependent mechanobiological and epigenetic changes in murine tenocytes. Our findings demonstrate that mature tenocytes generate higher traction forces and migrate faster. Furthermore, we reveal increased chromatin condensation in mature tenocytes, accompanied by elevated levels of the repressive histone mark H3K27me3 and reduced levels of the activating mark H3K4me3. Chromatin immunoprecipitation sequencing indicates that these histone modifications regulate genes associated with cellular contractility, ECM production, and mechanotransduction, highlighting the critical role of epigenetic mechanisms in governing tenocyte function. These findings suggest that age-related epigenetic changes may contribute to both the maintenance of tissue homeostasis and the suppression of degenerative diseases in tendons, providing new avenues for therapeutic strategies aimed at restoring tenocyte function and enhancing tendon regeneration.