title: AlphaVbeta3 integrin ligands enhance volume-sensitive calcium influx in mechanically stretched osteocytes.
abstract: 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.
authors.affiliation: National Hyogo Chuo Hospital, 1314 Ohara, Sanda, Hyogo, 669-1515, Japan. akiom@fiberbit.net
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Gotoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamioka
authors.forename: Kohei
authors.initials: K
authors.lastname: Notoya
authors.forename: Hideki
authors.initials: H
authors.lastname: Sekiya
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Takagi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yoshimoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chihara
authors.forename: Teruko
authors.initials: T
authors.lastname: Takano-Yamamoto
authors.forename: Takuo
authors.initials: T
authors.lastname: Fujita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mikuni-Takagaki
mesh_terms: 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
chemical_list: 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