Mechanosensory role and clinical potential of primary cilia in bone and tooth

Mechanical stimulation plays a crucial role in the health of hard tissues, involving multiple factors such as the extracellular matrix, cytoskeleton, dendritic processes, ion channels, integrin-based focal adhesions, and connexin-based intercellular junctions. Recent evidence highlights the pivotal role of primary cilia in mechanosensation related to the development and regeneration of hard tissues. Notably, mechanosensation by primary cilia is influenced by four key characteristics: length, rigidity, orientation, and basal body. Primary cilia employ several mechanosensory mechanisms, including ion channels, the cytoskeleton, and integrins. Disruption of primary cilia impairs mechanosensation, leading to compromised hard tissues homeostasis and other detrimental effects. Enhancing primary ciliary mechanosensation and chemosensation through drugs that increase primary ciliary length or protect and activate primary cilia can safeguard hard tissue health. This review aims to summarize the mechanosensory role and clinical potential of primary cilia in hard tissues, emphasizing their critical role in cellular responses to mechanical stimuli.