Osteoprotegerin, a new actor in vasculogenesis, stimulates endothelial colony-forming cells properties.
J Thromb Haemost
; 9(4): 834-43, 2011 Apr.
Article
em En
| MEDLINE
| ID: mdl-21255246
ABSTRACT
BACKGROUND:
Osteoprotegerin (OPG), a soluble receptor of the tumour necrosis factor family, and its ligand, the receptor activator of nuclear factor-κB 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(®) (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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Vasos Sanguíneos
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Neovascularização Fisiológica
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Osteoprotegerina
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article