Evidence map›Paper›PMID 24647000›Full record

ArticleNature2014

Endothelial Notch activity promotes angiogenesis and osteogenesis in bone.

Saravana K Ramasamy, Anjali P Kusumbe, Lin Wang, Ralf H Adams

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02750046 (Collection of Bone Specimens for Testing of A Special Vessel Subtype), which is not on this map. Cited by 597 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
597citing papers in PubMed, 3 pooled it
18.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02750046 naunknown statusnot on this mapstarted 2016, after this paper: background citation

Collection of Bone Specimens for Testing of A Special Vessel Subtype

TypeinterventionalSponsorSecond Affiliated Hospital of Soochow UniversityRan2016 to 2018Enrolled30ConditionsFemoral Neck FracturesArmstotal hip arthroplasty or proximal femoral nails
3 · Its place in the literature

Who cites it

597 citing papers in PubMed, 3 syntheses or guidelines pooled it, 995 citations in OpenAlex.

  1. Pooled it
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  6. Thioredoxin-2 Alleviates Osteoporosis by Restraining FOXO3a Nuclear Translocation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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537 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Saravana K Ramasamy *Max-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, Münster, German.
Anjali P Kusumbe *Max-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, Münster, German.
Lin WangMax-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, Münster, German.
Ralf H AdamsMax-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, Münster, German.
Max Planck Institute for Molecular Biomedicine · DEUniversity of Münster · DE

Funding

European Research Council 339409
6 · The paper itself

Abstract

Blood vessel growth in the skeletal system and osteogenesis seem to be coupled, suggesting the existence of molecular crosstalk between endothelial and osteoblastic cells. 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 tumours. 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.

Indexed as

Neovascularization, PhysiologicOsteogenesisAnimalsAnimals, NewbornBlood VesselsBone and BonesBone DevelopmentCalcification, PhysiologicCarrier ProteinsCell ProliferationChondrocytesEndothelium, VascularFemaleMaleMiceMice, Inbred C57BLCarrier ProteinsNoggin ProteinReceptors, Notch

Identifiers

PMID24647000
PMCPMC4943529
OpenAlexW2087363756

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.