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

(2010) EMBO JOURNAL. 29(2). p.424-441
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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
Keywords
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

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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.
@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},
}

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