Mechanosensitive structures. (a) Focal adhesions. Focal adhesions connect
ECM mechanical signals to the cytoskeleton, affecting cytoskeleton
arrangement and crosslinking; (b) Piezo1 and TRPV4. Activation of ion
channels by mechanical stimuli elicits specific ion flow, especially
calcium influx, to modulate downstream signaling pathways and cell
differentiation; (c) Primary cilium. When primary cilia bend under FSS,
TRPV4 ion channels open, allowing Ca2+ influx and MSCs
osteogenic differentiation. PTH1R translocation on primary cilia
prevents osteoclast activation by releasing IL-6 and CXCL5; (d) Cx43.
When osteocytes experience mechanical stimulation, the Cx43 protein is
phosphorylated, and the connexon is opened, allowing the exchange of
several effectors, such as calcium, ATP, PGE2, and Sost, between
connecting cells through gap junctions. Osteocytes with Cx43-silencing
undergo apoptosis via AKT/P27/Caspase-3 pathway. The graph was created
with BioRender.com.