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PROVEC SIGNED

Promoting Osteogenesis through Vascular Endothelial Cells

Total Cost €

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EC-Contrib. €

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Partnership

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 PROVEC project word cloud

Explore the words cloud of the PROVEC project. It provides you a very rough idea of what is the project "PROVEC" about.

trigger    successful    generate    single    signaling    regeneration    thereby    capillaries    osteoblast    endothelial    diseased    lineage    manipulation    mapping    expression    biology    mouse    vascular    27    regenerating    diseases    osteoblasts    confocal    fate    skeletal    monitored    combination    osteoprogenitors    cultures    hypoxia    form    pharmacological    modulation    notch    micro    lack    computational    models    euros    subpopulations    million    genetics    animal    transplantation    cells    insights    found    generates    genetic    imaging    ambitions    ct    completion    expansion    therapeutic    cultured    photon    cell    microscopy    appropriate    health    bone    aging    functional    treatments    heterogeneity    alone    crosstalk    organization    osteoporosis    osteoclasts    animals    gene    relevance    sufficient    rna    37    seq    endowed    healthy    sequencing    organoid    3d    inducible    provec    mineral    specialization    patients    vasculature    beneficial    mice    billion    ecs    density    living    preclinical    powerful    regulation    human    fundamental    disease    systemically    induce    annual   

Project "PROVEC" data sheet

The following table provides information about the project.

Coordinator
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV 

Organization address
address: HOFGARTENSTRASSE 8
city: MUENCHEN
postcode: 80539
website: n.a.

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 2˙205˙875 €
 EC max contribution 2˙205˙875 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-ADG
 Funding Scheme ERC-ADG
 Starting year 2019
 Duration (year-month-day) from 2019-02-01   to  2024-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (MUENCHEN) coordinator 2˙205˙875.00

Map

 Project objective

The skeletal system and its vasculature form a functional unit with great relevance in health, regeneration, and disease. Our recent work has provided fundamental insights into the organization of the bone vasculature in mouse, its changes during aging, the heterogeneity and functional specialization of bone capillaries and endothelial cells, the regulation of these properties by Notch and hypoxia-inducible factor signaling, and the crosstalk with osteoblast lineage cells. Most importantly, we found that the manipulation of ECs in the aging animal can trigger the expansion of osteoprogenitors and thereby induce bone formation. PROVEC will now systemically identify and characterize endothelial cell subpopulations, their gene expression and functional properties in the healthy, aging, diseased and regenerating skeletal system. Preclinical models will establish whether endothelial cells are involved in the response to therapeutic treatments aiming at osteoblasts or osteoclasts, or if the modulation of ECs alone is sufficient to generate beneficial effects. Finally, PROVEC will investigate whether cultured mouse and human ECs can be endowed with beneficial properties to enhance bone formation in 3D organoid cultures and after transplantation into mice, which will be monitored by imaging in living animals. To achieve its ambitions aims, PROVEC will use a powerful combination of mouse genetics, disease models, genetic fate mapping, RNA-seq and single cell sequencing, computational biology, confocal and 2-photon microscopy, micro-CT imaging, pharmacological treatments, and cell biology methods to establish if and how vascular endothelial cells can be used to increase bone mineral density in preclinical models. The successful completion of PROVEC would be highly relevant for diseases such as osteoporosis, which affects around 27.5 million patients in the EU, generates annual costs of about 37 billion Euros, and for which we currently lack appropriate treatments.

 Publications

year authors and title journal last update
List of publications.
2020 Kishor K Sivaraj, Backialakshmi Dharmalingam, Vishal Mohanakrishnan, Hyun-Woo Jeong, Katsuhiro Kato, Silke Schröder, Susanne Adams, Gou Young Koh, Ralf H Adams
YAP1 and TAZ negatively control bone angiogenesis by limiting hypoxia-inducible factor signaling in endothelial cells
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.50770
eLife 9 2020-02-06

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