Figure 1.

Down-regulation of SOST in osteocytes by mechanotransduction. Integrin αVβ3 in dendritic processes sense fluid flow shear stress (FFSS) applied on the extracellular matrix (ECM). The subsequent activation of phosphoinositide 3-kinase (PI3K) phosphorylates Akt, which activates integrin-mediated connexin 43 (Cx43) channel opening on the cellular body. Prostaglandin E2 (PGE2) is transported out of the osteocyte and binds to EP2 and EP4 receptors, which further activates the Akt and extracellular signal-regulated kinase (ERK) pathways and β-catenin, which down-regulates SOST expression. FFSS activates also Ca²⁺ influx through Piezo1 channels, which enables enhanced Akt activation. Black dotted arrows indicate transport through membrane channels. Created with BioRender.com, accessed on 15 February 2022.