Mechano-biology optimized cellular exercise for early OA regenerative therapy

Mechanical signals are key factors that contribute to homeostasis in the joint but also involved in the development of osteoarthritis (OA), the most common chronic joint disease affecting millions worldwide. Tissue loading and unloading cycles represent mechanical stimuli essential for the cells to maintain cartilage integrity by mechanotransduction. However, in early stages of OA this protective effect of physiological loading appears compromised, and chondrocytes shift their anabolism-catabolism balance. 

The mechanisms underlying this impaired response to loading remain elusive, hampering the development of strategies that delay or reverse disease progression. In this project I will address a fundamental knowledge gap: why is the protective effect of loading compromised in early OA? I hypothesise that the protective response to loading depends on the chondrocyte’s mechanical memory, which is inadequately tuned in the altered mechanical environment of early OA, yet can be ‘retrained’ through optimizing mechanotransduction pathways. To test this hypothesis, I will (i) outline the mechanisms of mechanical memory in chondrocytes, (ii) elucidate the impact of mechanical environment in the early OA and (iii) test the potential of biomechanical modulation of these parameters as a therapy to withstand the phenotypic molecular shift of early OA chondrocytes. 

If successful, the mechano-biological optimization of cartilage homeostasis could be a game-changer for treatment of OA.