TY - JOUR T1 - Osteoprotegerin, a new actor in vasculogenesis, stimulates endothelial colony-forming cells properties A1 - Benslimane-Ahmim,Z. A1 - Heymann,D. A1 - Dizier,B. A1 - Lokajczyk,A. A1 - Brion,R. A1 - Laurendeau,I. A1 - Bieche,I. A1 - Smadja,D. M. A1 - Galy-Fauroux,I. A1 - Colliec-Jouault,Sylvia A1 - Fischer,Anne-Marie A1 - Boisson-Vidal,Catherine AD - Fac Pharm, INSERM, U765, F-75270 Paris 06, France. AD - INSERM, UMR S 957, Nantes, France. AD - Nantes Atlantique Univ, Univ Nantes, Nantes, France. AD - Univ Paris Cite Paris Descartes, Fac Pharm, Paris, France. AD - INSERM, U745, Genet Mol Lab, Paris, France. AD - Hop Europeen Georges Pompidou, AP HP, Dept Haematol, Paris, France. AD - IFREMER, Nantes, France. UR - https://doi.org/10.1111/j.1538-7836.2011.04207.x DO - 10.1111/j.1538-7836.2011.04207.x KW - endothelial colony-forming cells KW - osteoprotegerin KW - receptor activator of nuclear factor-kappa B ligand KW - vasculogenesis N2 - Background: Osteoprotegerin (OPG), a soluble receptor of the tumour necrosis factor family, and its ligand, the receptor activator of nuclear factor-kappa B ligand (RANKL), are emerging as important regulators of vascular pathophysiology. Objectives: We evaluated their effects on vasculogenesis induced by endothelial colony-forming cells (ECFC) and on neovessel formation in vivo. Methods: Effects of OPG and RANKL on in vitro angiogenesis were evaluated after ECFC incubation with OPG or RANKL (0-50 ng mL(-1)). Effects on microvessel formation were evaluated with an in vivo murin Matrigel plug assay. Vascularization was evaluated by measuring plug hemoglobin and vascular endothelial growth factor (VEGF)-R2 content 14 days after implantation. Results: We found that ECFC expressed OPG and RANK but not RANKL mRNA. Treatment of ECFC with VEGF or stromal cell-derived factor-1 (SDF-1) upregulated OPG mRNA expression. OPG stimulated ECFC migration (P < 0.05), chemotaxis (P < 0.05) and vascular cord formation on Matrigel (R) (P < 0.01). These effects were correlated with SDF-1 mRNA overexpression, which was 30-fold higher after 4 h of OPG stimulation (P < 0.01). OPG-mediated angiogenesis involved the MAPK signaling pathway as well as Akt or mTOR cascades. RANKL also showed pro-vasculogenic effects in vitro. OPG combined with FGF-2 promoted neovessel formation in vivo, whereas RANKL had no effect. Conclusions: OPG induces ECFC activation and is a positive regulator of microvessel formation in vivo. Our results suggest that the OPG/RANK/RANKL axis may be involved in vasculogenesis and strongly support a modulatory role in tissue revascularization. Y1 - 2011/04 PB - Wiley-blackwell JF - Journal Of Thrombosis And Haemostasis SN - 1538-7933 VL - 9 IS - 4 SP - 834 EP - 843 ID - 14462 ER -