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Increased skeletal VEGF enhances β-catenin activity and results in excessively ossified bones

Christa Maes, Steven Goossens UGent, Sona Bartunkova UGent, Benjamin Drogat UGent, Lieven Coenegrachts, Ingrid Stockmans, Karen Moermans, Omar Nyabi, Katharina Haigh UGent, Michaël Naessens UGent, et al. (2010) EMBO JOURNAL. 29(2). p.424-441
abstract
Vascular endothelial growth factor (VEGF) and beta-catenin both act broadly in embryogenesis and adulthood, including in the skeletal and vascular systems. Increased or deregulated activity of these molecules has been linked to cancer and bone-related pathologies. By using novel mouse models to locally increase VEGF levels in the skeleton, we found that embryonic VEGF over-expression in osteo-chondroprogenitors and their progeny largely pheno-copied constitutive beta-catenin activation. Adult induction of VEGF in these cell populations dramatically increased bone mass, associated with aberrant vascularization, bone marrow fibrosis and haematological anomalies. Genetic and pharmacological interventions showed that VEGF increased bone mass through a VEGF receptor 2- and phosphatidyl inositol 3-kinase-mediated pathway inducing beta-catenin transcriptional activity in endothelial and osteoblastic cells, likely through modulation of glycogen synthase kinase 3-beta phosphorylation. These insights into the actions of VEGF in the bone and marrow environment underscore its power as pleiotropic bone anabolic agent but also warn for caution in its therapeutic use. Moreover, the finding that VEGF can modulate beta-catenin activity may have widespread physiological and clinical ramifications. The EMBO Journal (2010) 29, 424-441. doi: 10.1038/emboj.2009.361; Published online 10 December 2009
Please use this url to cite or link to this publication:
author
organization
alternative title
Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones
year
type
journalArticle (original)
publication status
published
subject
keyword
CONDITIONAL INACTIVATION, HEMATOPOIETIC STEM-CELL, GLYCOGEN-SYNTHASE KINASE-3, ENDOTHELIAL GROWTH-FACTOR, OSTEOCLAST DIFFERENTIATION, CHRONIC IDIOPATHIC MYELOFIBROSIS, VEGF, BLOOD-BRAIN-BARRIER, vasculature, skeleton, osteoblast, beta-catenin, MYELOID METAPLASIA, SIGNALING CONTROLS, PROGENITOR CELLS
journal title
EMBO JOURNAL
Embo J.
volume
29
issue
2
pages
18 pages
Web of Science type
Article
Web of Science id
000273731200014
JCR category
BIOCHEMISTRY & MOLECULAR BIOLOGY
JCR impact factor
10.124 (2010)
JCR rank
15/284 (2010)
JCR quartile
1 (2010)
ISSN
0261-4189
DOI
10.1038/emboj.2009.361
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
853261
handle
http://hdl.handle.net/1854/LU-853261
date created
2010-02-05 13:46:23
date last changed
2016-12-19 15:40:55
@article{853261,
  abstract     = {Vascular endothelial growth factor (VEGF) and beta-catenin both act broadly in embryogenesis and adulthood, including in the skeletal and vascular systems. Increased or deregulated activity of these molecules has been linked to cancer and bone-related pathologies. By using novel mouse models to locally increase VEGF levels in the skeleton, we found that embryonic VEGF over-expression in osteo-chondroprogenitors and their progeny largely pheno-copied constitutive beta-catenin activation. Adult induction of VEGF in these cell populations dramatically increased bone mass, associated with aberrant vascularization, bone marrow fibrosis and haematological anomalies. Genetic and pharmacological interventions showed that VEGF increased bone mass through a VEGF receptor 2- and phosphatidyl inositol 3-kinase-mediated pathway inducing beta-catenin transcriptional activity in endothelial and osteoblastic cells, likely through modulation of glycogen synthase kinase 3-beta phosphorylation. These insights into the actions of VEGF in the bone and marrow environment underscore its power as pleiotropic bone anabolic agent but also warn for caution in its therapeutic use. Moreover, the finding that VEGF can modulate beta-catenin activity may have widespread physiological and clinical ramifications. The EMBO Journal (2010) 29, 424-441. doi: 10.1038/emboj.2009.361; Published online 10 December 2009},
  author       = {Maes, Christa and Goossens, Steven and Bartunkova, Sona and Drogat, Benjamin and Coenegrachts, Lieven and Stockmans, Ingrid and Moermans, Karen and Nyabi, Omar and Haigh, Katharina and Naessens, Micha{\"e}l and Haenebalcke, Lieven and Tuckermann, Jan P and Tjwa, Marc and Carmeliet, Pieter and Mandic, Vice and David, Jean-Pierre and Behrens, Axel and Nagy, Andras and Carmeliet, Geert and Haigh, Jody},
  issn         = {0261-4189},
  journal      = {EMBO JOURNAL},
  keyword      = {CONDITIONAL INACTIVATION,HEMATOPOIETIC STEM-CELL,GLYCOGEN-SYNTHASE KINASE-3,ENDOTHELIAL GROWTH-FACTOR,OSTEOCLAST DIFFERENTIATION,CHRONIC IDIOPATHIC MYELOFIBROSIS,VEGF,BLOOD-BRAIN-BARRIER,vasculature,skeleton,osteoblast,beta-catenin,MYELOID METAPLASIA,SIGNALING CONTROLS,PROGENITOR CELLS},
  language     = {eng},
  number       = {2},
  pages        = {424--441},
  title        = {Increased skeletal VEGF enhances \ensuremath{\beta}-catenin activity and results in excessively ossified bones},
  url          = {http://dx.doi.org/10.1038/emboj.2009.361},
  volume       = {29},
  year         = {2010},
}

Chicago
Maes, Christa, Steven Goossens, Sona Bartunkova, Benjamin Drogat, Lieven Coenegrachts, Ingrid Stockmans, Karen Moermans, et al. 2010. “Increased Skeletal VEGF Enhances Β-catenin Activity and Results in Excessively Ossified Bones.” Embo Journal 29 (2): 424–441.
APA
Maes, Christa, Goossens, S., Bartunkova, S., Drogat, B., Coenegrachts, L., Stockmans, I., Moermans, K., et al. (2010). Increased skeletal VEGF enhances β-catenin activity and results in excessively ossified bones. EMBO JOURNAL, 29(2), 424–441.
Vancouver
1.
Maes C, Goossens S, Bartunkova S, Drogat B, Coenegrachts L, Stockmans I, et al. Increased skeletal VEGF enhances β-catenin activity and results in excessively ossified bones. EMBO JOURNAL. 2010;29(2):424–41.
MLA
Maes, Christa, Steven Goossens, Sona Bartunkova, et al. “Increased Skeletal VEGF Enhances Β-catenin Activity and Results in Excessively Ossified Bones.” EMBO JOURNAL 29.2 (2010): 424–441. Print.