Hyper-Physiologic Mechanical Loading Conditions Cause A Shift In The Epigenetic Landscape In Neo-Cartilage Organoids

Purpose: Osteoarthritis (OA) is a complex age-related multifactorial disease marked by articular cartilage degeneration. Chondrocytes, the sole cell type in articular cartilage, are responsible for maintaining the balance between an anabolic and catabolic state throughout life. A previous study showed that pathophysiology of OA is marked by a loss of epigenetic control of these post-mitotic cells to maintain their maturational arrested state. Among others, hyper-physiological mechanical stress is an important driver of the onset and progression of OA. In the current study, we postulate that hyper-physiological mechanical stress evokes persistent changes in set points of epigenetically regulated gene expression, that contribute to age-related loss of epigenetic control of their healthy maturational arrested state. We employed a human induced pluripotent stem cell (hiPSC) derived cartilage organoid model to study the epigenetically regulated transcriptome-wide changes in response to hyper-physiological mechanical loading conditions.