Evidence map›Paper›PMID 28716575›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017

Strategic Targeting of Multiple BMP Receptors Prevents Trauma-Induced Heterotopic Ossification.

Shailesh Agarwal, Shawn J Loder, Christopher Breuler, John Li, David Cholok, Cameron Brownley, Jonathan Peterson, Hsiao H Hsieh, James Drake, Kavitha Ranganathan and 10 more

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

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

44 citing papers in PubMed, 64 citations in OpenAlex.

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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

20 authors at 7 institutions in 1 country.

Shailesh AgarwalDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Shawn J LoderDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Christopher BreulerDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
John LiDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
David CholokDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Cameron BrownleyDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Jonathan PetersonDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Hsiao H HsiehDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
James DrakeDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Kavitha RanganathanDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Yashar S NiknafsDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Wenzhong XiaoStanford University, Palo Alto, CA 94305, USA.
Shuli LiDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Ravindra KumarAcceleron Pharma, Cambridge, MA 02139, USA.
Ronald TompkinsDepartment of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Michael T LongakerHagey Research Laboratory, Department of Surgery, Stanford University, Palo Alto, CA 94305, USA.
Thomas A DavisRegenerative Medicine Department, Naval Medical Research Center, Silver Spring, MD 20910, USA.
Paul B YuDepartment of Medicine, Harvard University, Boston, MA 02115, USA.
Yuji MishinaDepartment of Biological and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
Benjamin LeviDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: blevi@umich.edu.
University of Michigan · USAcceleron Pharma (United States) · USHarvard University · USMassachusetts General Hospital · USNaval Medical Research Command · USPalo Alto University · USStanford University · US

Funding

MICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3M
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 probes of BMP and TGF-beta signaling and functionR01AR057374 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI YU, PAUL B · 2010 to 2023
$4.5M
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 AR066947NIAMS NIH HHS R01 AR057374NIDCR NIH HHS R01 DE020843NIGMS NIH HHS K08 GM109105NIGMS NIH HHS T32 GM007863
6 · The paper itself

Abstract

Trauma-induced heterotopic ossification (tHO) is a condition of pathologic wound healing, defined by the progressive formation of ectopic bone in soft tissue following severe burns or trauma. Because previous studies have shown that genetic variants of HO, such as fibrodysplasia ossificans progressiva (FOP), are caused by hyperactivating mutations of the type I bone morphogenetic protein receptor (T1-BMPR) ACVR1/ALK2, studies evaluating therapies for HO have been directed primarily toward drugs for this specific receptor. However, patients with tHO do not carry known T1-BMPR mutations. Here we show that, although BMP signaling is required for tHO, no single T1-BMPR (ACVR1/ALK2, BMPR1a/ALK3, or BMPR1b/ALK6) alone is necessary for this disease, suggesting that these receptors have functional redundancy in the setting of tHO. By utilizing two different classes of BMP signaling inhibitors, we developed a translational approach to treatment, integrating treatment choice with existing diagnostic options. Our treatment paradigm balances either immediate therapy with reduced risk for adverse effects (Alk3-Fc) or delayed therapy with improved patient selection but greater risk for adverse effects (LDN-212854).

Indexed as

Gene TargetingActivin Receptors, Type IAnimalsAnti-Inflammatory AgentsBiomarkersBone Morphogenetic Protein ReceptorsBone Morphogenetic Protein Receptors, Type IGene Knockout TechniquesGenetic Predisposition to DiseaseHumansLigandsMacrophagesMiceMice, KnockoutNeutrophilsOssification, HeterotopicActivin Receptors, Type IACVR1 protein, humanAnti-Inflammatory AgentsBiomarkersBMPR1A protein, humanBMPR1B protein, humanBone Morphogenetic Protein ReceptorsBone Morphogenetic Protein Receptors, Type ILigandsProtein Kinase InhibitorsBMP receptorsBMP signalingstem cells

Identifiers

PMID28716575
PMCPMC5542633
OpenAlexW2590068411

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.