Evidence map›Paper›PMID 36200412›Full record

ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2023

Single-cell RNAseq provides insight into altered immune cell populations in human fracture nonunions.

Keith G Avin, James M Dominguez, Neal X Chen, Takashi Hato, Jered J Myslinski, Hongyu Gao, Yunlong Liu, Todd O McKinley, Krista M Brown, Sharon M Moe and 1 more

Open access · greenAbstract read
In one paragraph

Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
4.5field-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

26 citing papers in PubMed, 30 citations in OpenAlex.

  1. Bone reports · 2026
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  17. Advances on T cell immunity in bone remodeling and bone regeneration.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024
    Review
  18. Osteoimmunology of Fracture Healing.Current osteoporosis reports · 2024
    Review
  19. Article
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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

11 authors at 1 institution in 1 country.

Keith G AvinDepartment of Physical Therapy, School of Health and Human Sciences, Indiana University, Indianapolis, Indiana, USA.
James M DominguezDivision of Nephrology, School of Medicine, Indiana University, Indianapolis, Indiana, USA.
Neal X ChenDivision of Nephrology, School of Medicine, Indiana University, Indianapolis, Indiana, USA.
Takashi HatoDivision of Nephrology, School of Medicine, Indiana University, Indianapolis, Indiana, USA.
Jered J MyslinskiDivision of Nephrology, School of Medicine, Indiana University, Indianapolis, Indiana, USA.
Hongyu GaoDepartment of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, Indiana, USA.
Yunlong LiuDepartment of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, Indiana, USA.
Todd O McKinleyDepartment of Orthopaedic Surgery, School of Medicine, Indiana University, Indianapolis, Indiana, USA.ORCID 0000-0001-6354-7685
Krista M BrownDepartment of Orthopaedic Surgery, School of Medicine, Indiana University, Indianapolis, Indiana, USA.
Sharon M MoeDivision of Nephrology, School of Medicine, Indiana University, Indianapolis, Indiana, USA.
Roman M NatoliDepartment of Orthopaedic Surgery, School of Medicine, Indiana University, Indianapolis, Indiana, USA.ORCID 0000-0002-4182-3244
Indiana University Indianapolis · US

Funding

Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
Resource CoreP30AR072581 · NIAMS · INDIANA UNIVERSITY INDIANAPOLIS · PI STUART J WARDEN · 2017 to 2026
$8.3M
Pathogenesis of compromised bone quality and mechanics in chronic kidney disease.R01DK110871 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI ALLEN, MATTHEW R, MOE, SHARON M · 2016 to 2019
$1.8M
Mechanisms of Interventions to Ameliorate Sarcopenia in Chronic Kidney DiseaseK08DK110429 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI AVIN, KEITH G · 2016 to 2021
$718k
Enhancing Fatty Acid Oxidation Will Improve Skeletal Muscle & Enable Exercise Adaptation in CKDR03DK125665 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI AVIN, KEITH G · 2020 to 2021
$238k
NCATS NIH HHS UL1 TR002529NIAMS NIH HHS P30 AR072581NIDDK NIH HHS K08 DK110429NIDDK NIH HHS R01 DK110871NIDDK NIH HHS R03 DK125665
6 · The paper itself

Abstract

Nonunion describes bone fractures that fail to heal, resulting in the fracture callus failing to fully ossify or, in atrophic cases, not forming altogether. Fracture healing is regulated, in part, by the balance of proinflammatory and anti-inflammatory processes occurring within the bone marrow and surface cell populations. We sought to further understand the role of osteoimmunology (i.e., study of the close relationship between the immune system and bone) by examining immune cell gene expression via single-cell RNA sequencing of intramedullary canal tissue obtained from human patients with femoral nonunions. Intramedullary canal tissue samples obtained by reaming were collected at the time of surgical repair for femur fracture nonunion (n = 5) or from native bone controls when harvesting autologous bone graft (n = 4). Cells within the samples were isolated and analyzed using the Chromium Single-Cell System (10x Genomics Inc.) and Illumina sequencers. Twenty-three distinct cell clusters were identified, with higher cell proportions in the nonunion samples for monocytes and CD14 + dendritic cells (DCs), and lower proportions of T cells, myelocytes, and promyelocytes in nonunion samples. Gene expression differences were identified in each of the cell clusters from cell types associated with osteoimmunology, including CD14 + DC, monocytes, T cells, promyelocytes, and myelocytes. These results provide human-derived gene profiles that can further our understanding of pathways that may be a cause or a consequence of nonunion, providing the clinical rationale to focus on specific components of osteoimmunology. Clinical significance: The novel single-cell approach may lead to clinically relevant diagnostic biomarkers during earlier stages of nonunion development and/or investigation into therapeutic options.

Indexed as

Femoral FracturesFractures, UnunitedBony CallusFracture HealingHumansOsteogenesisRetrospective StudiesSingle-Cell Gene Expression AnalysisTreatment OutcomebonenonunionosteoimmunologyscRNAseqsingle-cell sequencing

Identifiers

PMID36200412
PMCPMC10335365
OpenAlexW4302763073

What OpenQuestion holds

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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.