Vascular Endothelial Growth Factor-d Activates Vegfr-3 Expressed in Osteoblasts Inducing Their Differentiation.
From: Dipartimento di Biologia Molecolare, Sezione Reumatologia, Universitá degli Studi di Siena, Via Fiorentina 1, 53100 Siena, Italy.
The Journal of biological chemistry
- Publish Date: Jun 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 26
- Pages: 17961-7
- Medium: Print
- Language: English
- Citation (JAMA): Orlandini Maurizio, Spreafico Adriano, Bardelli Monia, et al. Vascular Endothelial Growth Factor-d Activates Vegfr-3 Expressed in Osteoblasts Inducing Their Differentiation.. J. Biol. Chem. Jun 2006;281:17961-7
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.
Mesh Headings (Keywords): Aged, Animals, Animals, Newborn, Cell Differentiation, Cells, Cultured, Endothelium, Vascular, Female, Humans, Male, Mice, Middle Aged, Osteoblasts, Osteocalcin, Osteogenesis, RNA, Small Interfering, Recombinant Proteins, Signal Transduction, Umbilical Veins, Vascular Endothelial Growth Factor D, Vascular Endothelial Growth Factor Receptor-3
Check for Full Text / PubMed Unique Identifier (PMID): 16624815
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