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

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Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones. / Maes, Christa; Goossens, Steven; Bartunkova, Sonia; Drogat, Benjamin; Coenegrachts, Lieve; Stockmans, Ingrid; Moermans, Karen; Nyabi, Omar; Haigh, Katharina; Naessens, Michael; Haenebalcke, Lieven; Tuckermann, Jan P; Tjwa, Marc; Carmeliet, Peter; Mandic, Vice; David, Jean-Pierre; Behrens, Axel; Nagy, Andras; Carmeliet, Geert; Haigh, Jody J.

In: EMBO J, Vol. 29, No. 2, 20.01.2010, p. 424-41.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Maes, C, Goossens, S, Bartunkova, S, Drogat, B, Coenegrachts, L, Stockmans, I, Moermans, K, Nyabi, O, Haigh, K, Naessens, M, Haenebalcke, L, Tuckermann, JP, Tjwa, M, Carmeliet, P, Mandic, V, David, J-P, Behrens, A, Nagy, A, Carmeliet, G & Haigh, JJ 2010, 'Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones', EMBO J, vol. 29, no. 2, pp. 424-41. https://doi.org/10.1038/emboj.2009.361

APA

Maes, C., Goossens, S., Bartunkova, S., Drogat, B., Coenegrachts, L., Stockmans, I., Moermans, K., Nyabi, O., Haigh, K., Naessens, M., Haenebalcke, L., Tuckermann, J. P., Tjwa, M., Carmeliet, P., Mandic, V., David, J-P., Behrens, A., Nagy, A., Carmeliet, G., & Haigh, J. J. (2010). Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones. EMBO J, 29(2), 424-41. https://doi.org/10.1038/emboj.2009.361

Vancouver

Maes C, Goossens S, Bartunkova S, Drogat B, Coenegrachts L, Stockmans I et al. Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones. EMBO J. 2010 Jan 20;29(2):424-41. https://doi.org/10.1038/emboj.2009.361

Bibtex

@article{0bf29bad440f4676909ad907417d8874,
title = "Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones",
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.",
keywords = "Animals, Bone and Bones, Cell Differentiation, Cell Proliferation, Cells, Cultured, Endothelial Cells, Gene Expression Regulation, Developmental, Humans, Mesoderm, Mice, Mice, Transgenic, Morphogenesis, Osteoblasts, Phosphatidylinositol 3-Kinases, Stem Cells, Stromal Cells, Vascular Endothelial Growth Factor A, beta Catenin",
author = "Christa Maes and Steven Goossens and Sonia Bartunkova and Benjamin Drogat and Lieve Coenegrachts and Ingrid Stockmans and Karen Moermans and Omar Nyabi and Katharina Haigh and Michael Naessens and Lieven Haenebalcke and Tuckermann, {Jan P} and Marc Tjwa and Peter Carmeliet and Vice Mandic and Jean-Pierre David and Axel Behrens and Andras Nagy and Geert Carmeliet and Haigh, {Jody J}",
year = "2010",
month = jan,
day = "20",
doi = "10.1038/emboj.2009.361",
language = "English",
volume = "29",
pages = "424--41",
journal = "EMBO J",
issn = "0261-4189",
publisher = "NATURE PUBLISHING GROUP",
number = "2",

}

RIS

TY - JOUR

T1 - Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones

AU - Maes, Christa

AU - Goossens, Steven

AU - Bartunkova, Sonia

AU - Drogat, Benjamin

AU - Coenegrachts, Lieve

AU - Stockmans, Ingrid

AU - Moermans, Karen

AU - Nyabi, Omar

AU - Haigh, Katharina

AU - Naessens, Michael

AU - Haenebalcke, Lieven

AU - Tuckermann, Jan P

AU - Tjwa, Marc

AU - Carmeliet, Peter

AU - Mandic, Vice

AU - David, Jean-Pierre

AU - Behrens, Axel

AU - Nagy, Andras

AU - Carmeliet, Geert

AU - Haigh, Jody J

PY - 2010/1/20

Y1 - 2010/1/20

N2 - 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.

AB - 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.

KW - Animals

KW - Bone and Bones

KW - Cell Differentiation

KW - Cell Proliferation

KW - Cells, Cultured

KW - Endothelial Cells

KW - Gene Expression Regulation, Developmental

KW - Humans

KW - Mesoderm

KW - Mice

KW - Mice, Transgenic

KW - Morphogenesis

KW - Osteoblasts

KW - Phosphatidylinositol 3-Kinases

KW - Stem Cells

KW - Stromal Cells

KW - Vascular Endothelial Growth Factor A

KW - beta Catenin

U2 - 10.1038/emboj.2009.361

DO - 10.1038/emboj.2009.361

M3 - SCORING: Journal article

C2 - 20010698

VL - 29

SP - 424

EP - 441

JO - EMBO J

JF - EMBO J

SN - 0261-4189

IS - 2

ER -