Fig. 7
Illustration of ion channels involved in osteocyte mechanobiology. During osteocyte mechanotransduction, the earliest event that takes place is an increase in the intracellular Ca2+ concentration of the cells.113 This calcium mobilization process is first triggered by the activation of MSICs.114 Among all the MSICs, Piezo1 is a promising mechanogating ion channel in osteocyte mechanobiology. Piezo1 is a curved channel that is highly engaged with the cell membrane.119 Mechanical stimulation increases the osteocyte membrane tension, which further induces the opening of Piezo1 channels. Downstream effectors of Piezo1 channels include the Akt–Sost pathway,124 YAP/TAZ–Wnt pathway,120 and intracellular calcium signaling.124 Upon MSIC opening, ions are exchanged between the cytoplasm and extracellular environment. This process further changes the plasma membrane charge balance and induces the opening of VSCs.125 Interestingly, the calcium that undergoes flux induced by mechanical stimulation is derived from not only external fluid and medium but also sites of internal calcium storage, such as the endoplasmic reticulum.128 This calcium mobilization can activate downstream effectors, such as actomyosin, Erk1/2, PGE2, PAK, and osteopontin.115 Calcium mobilization also regulates ATP release in osteocytes upon mechanical stimulation.113
