Evidence map›Paper›PMID 19257813›Full record

ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2009

Sustained BMP signaling in osteoblasts stimulates bone formation by promoting angiogenesis and osteoblast differentiation.

Fengjie Zhang, Tao Qiu, Xiangwei Wu, Chao Wan, Weibin Shi, Ying Wang, Jian-guo Chen, Mei Wan, Thomas L Clemens, Xu Cao

Abstract read
In one paragraph

Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

38 citing papers in PubMed, 87 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Journal of orthopaedic translation · 2022
    Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Bone Morphogenetic Protein-Based Therapeutic Approaches.Cold Spring Harbor perspectives in biology · 2018
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. PTH receptor signaling in osteoblasts regulates endochondral vascularization in maintenance of postnatal growth plate.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2015
    Article
  19. Terbium promotes adhesion and osteogenic differentiation of mesenchymal stem cells via activation of the Smad-dependent TGF-β/BMP signaling pathway.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2014
    Article
  20. Review
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

10 authors at 3 institutions in 2 countries.

Fengjie ZhangDepartment of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Tao Qiu
Xiangwei Wu
Chao Wan
Weibin Shi
Ying Wang
Jian-guo Chen
Mei Wan
Thomas L Clemens
Xu Cao
University of Alabama at Birmingham · USHuazhong University of Science and Technology · CNShihezi University · CN

Funding

MECHANISM OF SMAD1 MEDIATED OSTEOBLAST DIFFERENTIATIONR01DK057501 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CAO, XU · 2001 to 2014
$3.8M
OXYGEN SENSING AND OSTEOGENESISR01AR049410 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CLEMENS, THOMAS L · 2004 to 2013
$3.2M
FUNCTION OF DNA VIRUS GENOMES IN ANIMAL CELLSZ01DK057501 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI OWENS, ROLAND ARVEL · 1986 to 2008
$846k
Intramural NIH HHS Z01 DK057501NIAMS NIH HHS AR049410NIAMS NIH HHS R01 AR049410NIDDK NIH HHS R01 DK057501
6 · The paper itself

Abstract

Angiogenesis and bone formation are tightly coupled during the formation of the skeleton. Bone morphogenetic protein (BMP) signaling is required for both bone development and angiogenesis. We recently identified endosome-associated FYVE-domain protein (endofin) as a Smad anchor for BMP receptor activation. Endofin contains a protein-phosphatase pp1c binding domain, which negatively modulates BMP signals through dephosphorylation of the BMP type I receptor. A single point mutation of endofin (F872A) disrupts interaction between the catalytic subunit pp1c and sensitizes BMP signaling in vitro. To study the functional impact of this mutation in vivo, we targeted expression of an endofin (F872A) transgene to osteoblasts. Mice expressing this mutant transgene had increased levels of phosphorylated Smad1 in osteoblasts and showed increased bone formation. Trabecular bone volume was significantly increased in the transgenic mice compared with the wildtype littermates with corresponding increases in trabecular bone thickness and number. Interestingly, the transgenic mice also had a pronounced increase in the density of the bone vasculature measured using contrast-enhanced microCT imaging of Microfil-perfused bones. The vessel surface and volume were both increased in association with elevated levels of vascular endothelial growth factor (VEGF) in osteoblasts. Endothelial sprouting from the endofin (F872A) mutant embryonic metatarsals cultured ex vivo was increased compared with controls and was abolished by an addition of a VEGF neutralizing antibody. In conclusion, osteoblast targeted expression of a mutant endofin protein lacking the pp1c binding activity results in sustained signaling of the BMP type I receptor, which increases bone formation and skeletal angiogenesis.

Indexed as

Amino Acid SubstitutionAnimalsBone Morphogenetic Protein Receptors, Type IBone Morphogenetic ProteinsCarrier ProteinsCatalytic DomainEmbryo, MammalianGTP-Binding ProteinsMiceMice, TransgenicMutation, MissenseNeovascularization, PhysiologicOsteogenesisPhosphorylationProtein Phosphatase 1Protein Structure, TertiaryBone Morphogenetic Protein Receptors, Type IBone Morphogenetic ProteinsCarrier ProteinsGTP-Binding ProteinsProtein Phosphatase 1SARA protein, mouseSmad1 ProteinSmad1 protein, mouseVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouse

Identifiers

PMID19257813
PMCPMC2697625
OpenAlexW2058143379

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.