AlphaVbeta3 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 alpha(V)beta(3) integrin, induced larger responses to the hypotonic swelling than other matrix molecules that bind other integrins. Addition of echistatin, which is a soluble alpha(V)beta(3) ligand, significantly enhanced the hypotonic [Ca(2+)](i) increase in addition to inducing an immediate increase in [Ca(2+)](i) by itself. These results strongly support the contention that alpha(V)beta(3) integrin signaling in osteocytes interacts with that in mechanotransduction, which is downstream of SA-Cat.
Miyauchi
Akimitsu
A
National Hyogo Chuo Hospital, 1314 Ohara, Sanda, Hyogo, 669-1515, Japan. akiom@fiberbit.net
Gotoh
Masayuki
M
Kamioka
Hiroshi
H
Notoya
Kohei
K
Sekiya
Hideki
H
Takagi
Yasuyuki
Y
Yoshimoto
Yoshio
Y
Ishikawa
Hitoshi
H
Chihara
Kazuo
K
Takano-Yamamoto
Teruko
T
Fujita
Takuo
T
Mikuni-Takagaki
Yuko
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002448:Cell Adhesion; D048429:Cell Size; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008024:Ligands; D009842:Oligopeptides / Q000494:pharmacology; D010011:Osteocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D053495:Osteopontin / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction; D013314:Stress, Mechanical; D013379:Substrate Specificity
D039302:Integrin alphaVbeta3; D008024:Ligands; D009842:Oligopeptides; C092614:glycyl-arginyl-glycyl-glutamyl-serine; D053495:Osteopontin; D015638:Cytochalasin D; C049554:glycyl-arginyl-glycyl-aspartyl-serine; D002118:Calcium