α_vβ₃ Integrin ligands enhance volume-sensitive calcium influx in mechanically stretched osteocytes

We propose that specific osteocyte-matrix interactions regulate the volume-sensitive calcium influx pathway, which we have shown is mediated by stretch-activated cation channels (SA-Cat) and is essential for the stretch-activated anabolic response in bone. The current study measured the hypotonic swelling-induced increase in cytosolic calcium concentration, [Ca ²⁺]_i, in rat osteocytes, and found that cells adherent to different matrices behave differently. Osteopontin and vitronectin, matrix molecules that bind the α_Vβ₃ integrin, induced larger responses to the hypotonic swelling than other matrix molecules that bind other integrins. Addition of echistatin, which is a soluble α_Vβ₃ ligand, significantly enhanced the hypotonic [Ca²⁺]_i increase in addition to inducing an immediate increase in [Ca²⁺]_i by itself. These results strongly support the contention that α_Vβ₃ integrin signaling in osteocytes interacts with that in mechanotransduction, which is downstream of SA-Cat.