Evidence map›Paper›PMID 27616463›Full record

ArticleScientific reports2016

Local and Circulating Endothelial Cells Undergo Endothelial to Mesenchymal Transition (EndMT) in Response to Musculoskeletal Injury.

Shailesh Agarwal, Shawn Loder, David Cholok, Joshua Peterson, John Li, David Fireman, Christopher Breuler, Hsiao Sung Hsieh, Kavitha Ranganathan, Charles Hwang and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

23 citing papers in PubMed, 28 citations in OpenAlex.

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  10. Heterotopic ossification of tendon and ligament.Journal of cellular and molecular medicine · 2020
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  11. The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition.Proceedings of the National Academy of Sciences of the United States of America · 2020
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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

15 authors at 2 institutions in 1 country.

Shailesh AgarwalBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Shawn LoderBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
David CholokBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Joshua PetersonBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
John LiBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
David FiremanBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Christopher BreulerBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Hsiao Sung HsiehBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Kavitha RanganathanBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Charles HwangBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
James DrakeBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Shuli LiBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Charles K ChanDepartment of Surgery, Stanford University, Stanford, CA 94305, USA.
Michael T LongakerDepartment of Surgery, Stanford University, Stanford, CA 94305, USA.
Benjamin LeviBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
University of Michigan–Ann Arbor · USStanford University · US

Funding

Induced pluripotent stem cells in the understanding and treatment of heart diseaseU01HL099776 · NHLBI · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T, WU, JOSEPH C. · 2009 to 2015
$8.2M
Molecular pathogenesis of craniosynostosis caused by enhanced BMP signalingR01DE020843 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MISHINA, YUJI · 2010 to 2019
$4.9M
Novel Pathway and Prevention Strategy for Heterotopic OssificationK08GM109105 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LEVI, BENJAMIN · 2014 to 2017
$785k
Targeting Heterotopic Ossification Induced Joint Contractures Before They Occur Through Early Detection and Angiogenic InhibitionF32AR068902 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RANGANATHAN, KAVITHA · 2015 to 2016
$116k
Targeting Inflammation and BMP Signaling in Osteoprogenitor Cells of Heterotopic OssificationF32AR066499 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI AGARWAL, SHAILESH · 2015 to 2015
$54k
Howard Hughes Medical InstituteNHLBI NIH HHS U01 HL099776NIAMS NIH HHS F32 AR066499NIAMS NIH HHS F32 AR068902NIAMS NIH HHS L30 AR066947NIDCR NIH HHS R01 DE020843NIGMS NIH HHS K08 GM109105
6 · The paper itself

Abstract

Endothelial-to-mesenchymal transition (EndMT) has been implicated in a variety of aberrant wound healing conditions. However, unambiguous evidence of EndMT has been elusive due to limitations of in vitro experimental designs and animal models. In vitro experiments cannot account for the myriad ligands and cells which regulate differentiation, and in vivo tissue injury models may induce lineage-independent endothelial marker expression in mesenchymal cells. By using an inducible Cre model to mark mesenchymal cells (Scx-creERT/tdTomato + ) prior to injury, we demonstrate that musculoskeletal injury induces expression of CD31, VeCadherin, or Tie2 in mesenchymal cells. VeCadherin and Tie2 were expressed in non-endothelial cells (CD31-) present in marrow from uninjured adult mice, thereby limiting the specificity of these markers in inducible models (e.g. VeCadherin- or Tie2-creERT). However, cell transplantation assays confirmed that endothelial cells (ΔVeCadherin/CD31+/CD45-) isolated from uninjured hindlimb muscle tissue undergo in vivo EndMT when transplanted directly into the wound without intervening cell culture using PDGFRα, Osterix (OSX), SOX9, and Aggrecan (ACAN) as mesenchymal markers. These in vivo findings support EndMT in the presence of myriad ligands and cell types, using cell transplantation assays which can be applied for other pathologies implicated in EndMT including tissue fibrosis and atherosclerosis. Additionally, endothelial cell recruitment and trafficking are potential therapeutic targets to prevent EndMT.

Indexed as

AggrecansAnimalsBurns, ElectricCadherinsCell DifferentiationEndothelial CellsEpithelial-Mesenchymal TransitionGene ExpressionHindlimbLeukocyte Common AntigensLuminescent ProteinsMaleMesenchymal Stem CellsMiceMice, Inbred C57BLMice, TransgenicAggrecansCadherinsLeukocyte Common AntigensLuminescent ProteinsPlatelet Endothelial Cell Adhesion Molecule-1Ptprc protein, mouseReceptor, Platelet-Derived Growth Factor alphaReceptor, TIE-2Red Fluorescent ProteinSox9 protein, mouseSOX9 Transcription FactorSp7 protein, mouseSp7 Transcription FactorTek protein, mouse

Identifiers

PMID27616463
PMCPMC5018841
OpenAlexW2518951951

What OpenQuestion holds

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LicenceCC BY
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.