Evidence map›Paper›PMID 22886301›Full record

ArticleThe Journal of clinical investigation2012

Intracellular VEGF regulates the balance between osteoblast and adipocyte differentiation.

Yanqiu Liu, Agnes D Berendsen, Shidong Jia, Sutada Lotinun, Roland Baron, Napoleone Ferrara, Bjorn R Olsen

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
175citing papers in PubMed, 1 pooled it
15.6field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

175 citing papers in PubMed, 1 synthesis or guideline pooled it, 352 citations in OpenAlex.

  1. Pooled it
  2. A BioLiving Periosteum Evokes Centripetal Regeneration in Challenging Bone Defects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  7. Optimizing type H vessels formationBioactive materials · 2025
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  11. Extracellular vesicles in bone aging: therapeutic strategies and applications.Extracellular vesicles and circulating nucleic acids · 2025
    Review
  12. Article
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  16. Article
  17. Sphingosine-1-phosphate promotes osteogenesis by stimulating osteoblast growth and neovascularization in a vascular endothelial growth factor-dependent manner.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024
    Article
  18. Article
  19. Review
  20. [Research progress on mechanism of traumatic brain injury promoting fracture healing].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2024
    Article

115 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Yanqiu LiuDepartment of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, USA. yanqiu_liu@post.harvard.edu
Agnes D Berendsen
Shidong Jia
Sutada Lotinun
Roland Baron
Napoleone Ferrara
Bjorn R Olsen
Harvard University · US

Funding

Pathogenic mechanisms of venous anomaliesP01AR048564 · NIAMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI OLSEN, BJORN REINO · 2003 to 2013
$13.4M
STRUCTURE OF TYPE I AND TYPE II PROCOLLAGENSR01AR036819 · NIAMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI OLSEN, BJORN REINO · 1986 to 2016
$8.7M
COLLAGEN GENE STRUCTURE AND EXPRESSIONR01AR036820 · NIAMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI OLSEN, BJORN REINO · 1986 to 2013
$6.7M
BIOGENESIS OF EXTRACELLULAR MATRIXR37AR036819 · NIAMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI OLSEN, BJORN R · 1992 to 2001
$827k
COLLAGEN GENE STRUCTURE AND EXPRESSIONR37AR036820 · NIAMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI OLSEN, BJORN R · 1993 to 1995
–
NIAMS NIH HHS AR36819NIAMS NIH HHS AR36820NIAMS NIH HHS AR48564NIAMS NIH HHS P01 AR048564NIAMS NIH HHS R01 AR036819NIAMS NIH HHS R01 AR036820NIAMS NIH HHS R37 AR036819
6 · The paper itself

Abstract

Osteoporotic bones have reduced spongy bone mass, altered bone architecture, and increased marrow fat. Bone marrow stem cells from osteoporotic patients are more likely to differentiate into adipocytes than control cells, suggesting that adipocyte differentiation may play a role in osteoporosis. VEGF is highly expressed in osteoblastic precursor cells and is known to stimulate bone formation. Here we tested the hypothesis that VEGF is also an important regulator of cell fate, determining whether differentiation gives rise to osteoblasts or adipocytes. Mice with conditional VEGF deficiency in osteoblastic precursor cells exhibited an osteoporosis-like phenotype characterized by reduced bone mass and increased bone marrow fat. In addition, reduced VEGF expression in mesenchymal stem cells resulted in reduced osteoblast and increased adipocyte differentiation. Osteoblast differentiation was reduced when VEGF receptor 1 or 2 was knocked down but was unaffected by treatment with recombinant VEGF or neutralizing antibodies against VEGF. Our results suggested that VEGF controls differentiation in mesenchymal stem cells by regulating the transcription factors RUNX2 and PPARγ2 as well as through a reciprocal interaction with nuclear envelope proteins lamin A/C. Importantly, our data support a model whereby VEGF regulates differentiation through an intracrine mechanism that is distinct from the role of secreted VEGF and its receptors.

Indexed as

Cell DifferentiationAdipocytesAdiposityAlkaline PhosphataseAnimalsBone DensityBone MarrowBone Marrow CellsCells, CulturedColony-Forming Units AssayCore Binding Factor Alpha 1 SubunitFemurGene ExpressionGene Expression RegulationLamin Type AMaleAlkaline PhosphataseCore Binding Factor Alpha 1 Subunitlamin CLamin Type APPAR gammaRunx2 protein, mouseVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouseVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2

Identifiers

PMID22886301
PMCPMC3428080
OpenAlexW2158135268

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.