Vascular endothelial growth factor (VEGF)-D is a member of the VEGF family of angiogenic growth factors that recognizes and activates the vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3 on blood and/or lymphatic vessels. We show that in the long bones of newborn mice, VEGF-D and VEGFR-3 are expressed in the osteoblasts of the growing plate. The treatment of primary human osteoblasts with recombinant VEGF-D induces the expression of osteocalcin and the formation of mineralized nodules in a dose-dependent manner. A monoclonal neutralizing antibody, anti-VEGF-D, or silencing of VEGFR-3 by lentiviral-mediated expression of VEGFR-3 small hairpin RNA affects VEGF-D-dependent osteocalcin expression and nodule formation. Moreover, in primary human osteoblasts, VEGF-D expression is under the control of VEGF, and inhibition of VEGF-D/VEGFR-3 signaling, by monoclonal antibodies or VEGFR-3 silencing, affects VEGF-dependent osteoblast differentiation. These experiments establish that VEGF-D/VEGFR-3 signaling plays a critical role in osteoblast maturation and suggest that VEGF-D is a downstream effector of VEGF in osteogenesis.

Orlandini, M., Spreafico, A., Bardelli, M., Rocchigiani, M., Salameh, A., Nucciotti, S., et al. (2006). Vascular endothelial growth factor-D activates VEGFR-3 expressed in osteoblasts inducing their differentiation. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 281(26), 17961-17967 [10.1074/jbc.M600413200].

Vascular endothelial growth factor-D activates VEGFR-3 expressed in osteoblasts inducing their differentiation

Orlandini, Maurizio;Rocchigiani, Marina;Frediani, Bruno;
2006-01-01

Abstract

Vascular endothelial growth factor (VEGF)-D is a member of the VEGF family of angiogenic growth factors that recognizes and activates the vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3 on blood and/or lymphatic vessels. We show that in the long bones of newborn mice, VEGF-D and VEGFR-3 are expressed in the osteoblasts of the growing plate. The treatment of primary human osteoblasts with recombinant VEGF-D induces the expression of osteocalcin and the formation of mineralized nodules in a dose-dependent manner. A monoclonal neutralizing antibody, anti-VEGF-D, or silencing of VEGFR-3 by lentiviral-mediated expression of VEGFR-3 small hairpin RNA affects VEGF-D-dependent osteocalcin expression and nodule formation. Moreover, in primary human osteoblasts, VEGF-D expression is under the control of VEGF, and inhibition of VEGF-D/VEGFR-3 signaling, by monoclonal antibodies or VEGFR-3 silencing, affects VEGF-dependent osteoblast differentiation. These experiments establish that VEGF-D/VEGFR-3 signaling plays a critical role in osteoblast maturation and suggest that VEGF-D is a downstream effector of VEGF in osteogenesis.
2006
Orlandini, M., Spreafico, A., Bardelli, M., Rocchigiani, M., Salameh, A., Nucciotti, S., et al. (2006). Vascular endothelial growth factor-D activates VEGFR-3 expressed in osteoblasts inducing their differentiation. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 281(26), 17961-17967 [10.1074/jbc.M600413200].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/20961