Evidence map›Paper›PMID 30786091›Full record

ArticleStem cells (Dayton, Ohio)2019

Coordinating Tissue Regeneration Through Transforming Growth Factor-β Activated Kinase 1 Inactivation and Reactivation.

Hsiao Hsin Sung Hsieh, Shailesh Agarwal, David J Cholok, Shawn J Loder, Kieko Kaneko, Amanda Huber, Michael T Chung, Kavitha Ranganathan, Joe Habbouche, John Li and 21 more

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

Article in Stem cells (Dayton, Ohio), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

9 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Deciphering the Regulatory Networks of the Migrasome-Associated Cell Subpopulation in Heterotopic Ossification via Multi-Omics Analysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Mechanisms of bone development and repair.Nature reviews. Molecular cell biology · 2020
    Review
  8. Article
  9. 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

31 authors at 8 institutions in 3 countries.

Hsiao Hsin Sung HsiehDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Shailesh AgarwalDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
David J CholokDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Shawn J LoderDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Kieko KanekoDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Amanda HuberDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Michael T ChungDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Kavitha RanganathanDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Joe HabboucheDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
John LiDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Jonathan ButtsDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Jonathan ReimerDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Arminder KauraDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
James DrakeDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Christopher BreulerDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Caitlin R PriestDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Joe NguyenSchool of Dentistry, University of Michigan, Ann Arbor, Michigan, USA.
Cameron BrownleyDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Jonathan PetersonDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Serra Ucer OzgurelDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Yashar S NiknafsDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Shuli LiDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Maiko InagakiDepartment of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina, USA.
Greg ScottKnock Out Core, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Paul H KrebsbachSection of Periodontics, UCLA School of Dentistry, Los Angeles, California, USA.
Michael T LongakerInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
Kenneth WestoverDepartment of Biochemistry, University of Texas Southwestern, Dallas, Texas, USA.
Nathanael GrayDana-Farber Cancer Institute, Boston, Massachusetts, USA.
Jun Ninomiya-TsujiDepartment of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina, USA.
Yuji MishinaSchool of Dentistry, University of Michigan, Ann Arbor, Michigan, USA.
Benjamin LeviDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
University of Michigan · USNorth Carolina State University · USCalifornia Institute for Regenerative Medicine · USDana-Farber Cancer Institute · USNational Institutes of Health · USRadboud University Nijmegen · NLThe University of Texas Southwestern Medical Center · USUniversity of California, Los Angeles · US

Funding

NIEHS Knock Out Mouse Core (KOMC) Annual ReportZICES102425 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI RAY, MANAS · 2010 to 2025
$20.1M
Structure, Composition, & Histology Core - Core BP30AR069620 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KARL J JEPSEN · 2016 to 2026
$8.4M
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
Targeting Molecular and Cellular Mediators of Inflammation to Prevent Pathologic Cell Differentiation and Heterotopic OssificationR01AR071379 · NIAMS · UT SOUTHWESTERN MEDICAL CENTER · PI LEVI, BENJAMIN · 2017 to 2021
$1.5M
Developing New Diagnostic and Timed, TAK1 Specific Treatment Strategies for Trauma Induced Heterotopic OssificationR01GM123069 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI LEVI, BENJAMIN · 2017 to 2020
$1.2M
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 Institute (HHMI) Medical Fellows ProgramNHLBI NIH HHS U01 HL099776NIAMS NIH HHS F32 AR066499NIAMS NIH HHS F32 AR068902NIAMS NIH HHS L30 AR066947NIAMS NIH HHS P30 AR069620NIAMS NIH HHS R01 AR071379NIDCR NIH HHS R01 DE020843NIGMS NIH HHS K08 GM109105NIGMS NIH HHS R01 GM123069
6 · The paper itself

Abstract

Aberrant wound healing presents as inappropriate or insufficient tissue formation. Using a model of musculoskeletal injury, we demonstrate that loss of transforming growth factor-β activated kinase 1 (TAK1) signaling reduces inappropriate tissue formation (heterotopic ossification) through reduced cellular differentiation. Upon identifying increased proliferation with loss of TAK1 signaling, we considered a regenerative approach to address insufficient tissue production through coordinated inactivation of TAK1 to promote cellular proliferation, followed by reactivation to elicit differentiation and extracellular matrix production. Although the current regenerative medicine paradigm is centered on the effects of drug treatment ("drug on"), the impact of drug withdrawal ("drug off") implicit in these regimens is unknown. Because current TAK1 inhibitors are unable to phenocopy genetic Tak1 loss, we introduce the dual-inducible COmbinational Sequential Inversion ENgineering (COSIEN) mouse model. The COSIEN mouse model, which allows us to study the response to targeted drug treatment ("drug on") and subsequent withdrawal ("drug off") through genetic modification, was used here to inactivate and reactivate Tak1 with the purpose of augmenting tissue regeneration in a calvarial defect model. Our study reveals the importance of both the "drug on" (Cre-mediated inactivation) and "drug off" (Flp-mediated reactivation) states during regenerative therapy using a mouse model with broad utility to study targeted therapies for disease. Stem Cells 2019;37:766-778.

Indexed as

AnimalsBone RegenerationCell DifferentiationCell ProliferationDNA NucleotidyltransferasesFemaleFounder EffectFractures, BoneGene Expression RegulationIntegrasesMaleMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesMesenchymal Stem CellsMiceMice, Inbred C57BLCre recombinaseDNA NucleotidyltransferasesFLP recombinaseIntegrasesMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesProtein Kinase InhibitorsCellular proliferationDifferentiationProgenitor cellsProliferationStem/progenitor cellTissue regeneration

Identifiers

PMID30786091
PMCPMC6542699
OpenAlexW2918045937

What OpenQuestion holds

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Registered trials

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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.