Evidence map›Paper›PMID 28297577›Full record

ArticleStem cells translational medicine2017

Surgical Excision of Heterotopic Ossification Leads to Re-Emergence of Mesenchymal Stem Cell Populations Responsible for Recurrence.

Shailesh Agarwal, Shawn Loder, David Cholok, John Li, Chris Breuler, James Drake, Cameron Brownley, Joshua Peterson, Shuli Li, Benjamin Levi

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

Article in Stem cells translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.5field-weighted citation impact, top 6% 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

47 citing papers in PubMed, 63 citations in OpenAlex.

  1. Piezo2FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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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

10 authors at 1 institution in 1 country.

Shailesh AgarwalBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Shawn LoderBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
David CholokBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
John LiBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Chris BreulerBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
James DrakeBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Cameron BrownleyBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Joshua PetersonBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Shuli LiBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Benjamin LeviBurn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
University of Michigan–Ann Arbor · US

Funding

Novel Pathway and Prevention Strategy for Heterotopic OssificationK08GM109105 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LEVI, BENJAMIN · 2014 to 2017
$785k
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 InstituteNIAMS NIH HHS F32 AR066499NIAMS NIH HHS L30 AR066947NIGMS NIH HHS K08 GM109105
6 · The paper itself

Abstract

Trauma-induced heterotopic ossification (HO) occurs after severe musculoskeletal injuries and burns, and presents a significant barrier to patient rehabilitation. Interestingly, the incidence of HO significantly increases with repeated operations and after resection of previous HO. Treatment of established heterotopic ossification is challenging because surgical excision is often incomplete, with evidence of persistent heterotopic bone. As a result, patients may continue to report the signs or symptoms of HO, including chronic pain, nonhealing wounds, and joint restriction. In this study, we designed a model of recurrent HO that occurs after surgical excision of mature HO in a mouse model of hind-limb Achilles' tendon transection with dorsal burn injury. We first demonstrated that key signaling mediators of HO, including bone morphogenetic protein signaling, are diminished in mature bone. However, upon surgical excision, we have noted upregulation of downstream mediators of osteogenic differentiation, including pSMAD 1/5. Additionally, surgical excision resulted in re-emergence of a mesenchymal cell population marked by expression of platelet-derived growth factor receptor-α (PDGFRα) and present in the initial developing HO lesion but absent in mature HO. In the recurrent lesion, these PDGFRα+ mesenchymal cells are also highly proliferative, similar to the initial developing HO lesion. These findings indicate that surgical excision of HO results in recurrence through similar mesenchymal cell populations and signaling mechanisms that are present in the initial developing HO lesion. These results are consistent with findings in patients that new foci of ectopic bone can develop in excision sites and are likely related to de novo formation rather than extension of unresected bone. Stem Cells Translational Medicine 2017;6:799-806.

Indexed as

AnimalsArthroplastyBone Morphogenetic ProteinsCartilageCell ProliferationChondrogenesisHipHumansMaleMesenchymal Stem CellsMice, Inbred C57BLOssification, HeterotopicOsteogenesisRecurrenceSignal TransductionBone Morphogenetic ProteinsBoneChondrogenesisExtremity traumaHeterotopic ossificationMesenchymal stem cellTissue regeneration

Identifiers

PMID28297577
PMCPMC5442786
OpenAlexW2529322243

What OpenQuestion holds

Textmetadata
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.