[alpha]V[beta]3 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^sup 2+^]^sub i^, in rat osteocytes, and found that cells adherent to different matrices behave differently. Osteopontin and vitronectin, matrix molecules that bind the α^sub V^β^sub 3^ integrin, induced larger responses to the hypotonic swelling than other matrix molecules that bind other integrins. Addition of echistatin, which is a soluble α^sub V^β^sub 3^ ligand, significantly enhanced the hypotonic [Ca^sup 2+^]^sub i^ increase in addition to inducing an immediate increase in [Ca^sup 2+^]^sub i^ by itself. These results strongly support the contention that α^sub V^β^sub 3^ integrin signaling in osteocytes interacts with that in mechanotransduction, which is downstream of SA-Cat.[PUBLICATION ABSTRACT]