The aim of this Wellcome Trust funded research project is to test the hypothesis that the primary cilium acts as a fundamental mechanoreceptor in articular chondrocytes triggering mechanosensitive intracellular calcium signalling via a purinergic pathway that involves the release of ATP. We will elucidate the underlying physiological mechanisms involved in ATP release and how this pathway is modulated by loading conditions. We will further investigate the effect of pathway activation on subsequent downstream anabolic and catabolic responses and the presence of signalling elements in diseased cartilage.