Role of α_v 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 α_vβ₃ or integrin α_vβ₅ blocking antibody inhibits endothelial cell migration. In contrast, treatment with anti-α_vβ₃ antibody or anti-α_vβ₅ 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 α_v activity. Taken together, these results suggest that integrins α_vβ₃ and/or α_vβ₅ contribute to endothelial cell proliferation and migration induced by OPG.