Role of αv integrin in osteoprotegerin-induced endothelial cell migration and proliferation

Osteoprotegerin (OPG) is a decoy receptor for the receptor activator of nuclear factor κB 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 αvβ3 or integrin αvβ5 blocking antibody inhibits endothelial cell migration. In contrast, treatment with anti-αvβ3 antibody or anti-αvβ5 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 αv activity. Taken together, these results suggest that integrins αvβ3 and/or αvβ5 contribute to endothelial cell proliferation and migration induced by OPG.