Imperial College London
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DrSaravanaRamasamy

Faculty of Medicine, National Heart & Lung Institute

Advanced Research Fellow
 
 
 
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Contact

 

+44 (0)20 3313 1182s.ramasamy Website

 
 
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Location

 

CRB 2003Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ramasamy:2014:10.1038/nature13146,
author = {Ramasamy, SK and Kusumbe, AP and Wang, L and Adams, RH},
doi = {10.1038/nature13146},
journal = {Nature},
pages = {376--380},
title = {Endothelial Notch activity promotes angiogenesis and osteogenesis in bone},
url = {http://dx.doi.org/10.1038/nature13146},
volume = {507},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Blood vessel growth in the skeletal system and osteogenesis seem to be coupled, suggesting the existence of molecular crosstalk between endothelial and osteoblastic cells1,2. Understanding the nature of the mechanisms linking angiogenesis and bone formation should be of great relevance for improved fracture healing or prevention of bone mass loss. Here we show that vascular growth in bone involves a specialized, tissue-specific form of angiogenesis. Notch signalling promotes endothelial cell proliferation and vessel growth in postnatal long bone, which is the opposite of the well-established function of Notch and its ligand Dll4 in the endothelium of other organs and tumours3,4. Endothelial-cell-specific and inducible genetic disruption of Notch signalling in mice not only impaired bone vessel morphology and growth, but also led to reduced osteogenesis, shortening of long bones, chondrocyte defects, loss of trabeculae and decreased bone mass. On the basis of a series of genetic experiments, we conclude that skeletal defects in these mutants involved defective angiocrine release of Noggin from endothelial cells, which is positively regulated by Notch. Administration of recombinant Noggin, a secreted antagonist of bone morphogenetic proteins, restored bone growth and mineralization, chondrocyte maturation, the formation of trabeculae and osteoprogenitor numbers in endothelial-cell-specific Notch pathway mutants. These findings establish a molecular framework coupling angiogenesis, angiocrine signals and osteogenesis, which may prove significant for the development of future therapeutic applications.
AU  - Ramasamy,SK
AU  - Kusumbe,AP
AU  - Wang,L
AU  - Adams,RH
DO  - 10.1038/nature13146
EP  - 380
PY  - 2014///
SN  - 0028-0836
SP  - 376
TI  - Endothelial Notch activity promotes angiogenesis and osteogenesis in bone
T2  - Nature
UR  - http://dx.doi.org/10.1038/nature13146
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000333029000038&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/nature13146
VL  - 507
ER  -
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