Role of alphav integrin in osteoprotegerin-induced endothelial cell migration and proliferation.
Osteoprotegerin (OPG) is a decoy receptor for the receptor activator of nuclear factor kappaB ligand (RANKL). However, the role of OPG in the endothelium remains unknown. In this study, we demonstrate that OPG stimulates the proliferation and migration of human microvascular endothelial cells (HMVECs). In addition, we show that treatment with integrin alpha(v)beta(3) or integrin alpha(v)beta(5) blocking antibody inhibits endothelial cell migration. In contrast, treatment with anti-alpha(v)beta(3) antibody or anti-alpha(v)beta(5) antibody alone did not inhibit OPG-induced proliferation. However, OPG-induced proliferation was inhibited when these antibodies were applied simultaneously. Furthermore, OPG evoked activation of extracellular signal-regulated kinase (ERK) 1/2, which has been linked to integrin alpha(v) activity. Taken together, these results suggest that integrins alpha(v)beta(3) and/or alpha(v)beta(5) contribute to endothelial cell proliferation and migration induced by OPG.
Kobayashi-Sakamoto
Michiyo
M
Department of Disease Control and Molecular Epidemiology, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, 1757, Hokkaido 061-0293, Japan. mkoba@hoku-iryo-u.ac.jp
Isogai
Emiko
E
Hirose
Kimiharu
K
Chiba
Itsuo
I
D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D039564:Integrin alphaV / Q000502:physiology*; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053244:Osteoprotegerin / Q000494:pharmacology* / Q000502:physiology; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D019096:Vitronectin / Q000502:physiology
D039564:Integrin alphaV; D039302:Integrin alphaVbeta3; D053244:Osteoprotegerin; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; C506030:TNFRSF11B protein, human; D019096:Vitronectin; C064660:integrin alphaVbeta5