Evidence map›Paper›PMID 32096907›Full record

ArticleAging cell2020

Age-related changes to macrophages are detrimental to fracture healing in mice.

Daniel Clark, Sloane Brazina, Frank Yang, Diane Hu, Christine L Hsieh, Erene C Niemi, Theodore Miclau, Mary C Nakamura, Ralph Marcucio

Open access · goldAbstract read
In one paragraph

Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 1 pooled it
6.1field-weighted citation impact, top 3% 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

80 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Murine Progeria Model Exhibits Delayed Fracture Healing With Senescent Phenotype and Dysregulated Immune Response.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Engineering Efferocytosis for Bone Regeneration.Macromolecular bioscience · 2025
    Review
  13. Article
  14. Article
  15. Observational
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

20 more citing papers are in PubMed but not listed here.

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

9 authors at 2 institutions in 1 country.

Daniel ClarkDepartment of Orthopaedic Surgery, School of Medicine, Orthopaedic Trauma Institute, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-3453-6498
Sloane BrazinaDepartment of Orthopaedic Surgery, School of Medicine, Orthopaedic Trauma Institute, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA.
Frank YangDepartment of Orthopaedic Surgery, School of Medicine, Orthopaedic Trauma Institute, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA.
Diane HuDepartment of Orthopaedic Surgery, School of Medicine, Orthopaedic Trauma Institute, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA.
Christine L HsiehDivision of Rheumatology, Department of Medicine, San Francisco VA Health Care System, San Francisco, CA, USA.
Erene C NiemiDivision of Rheumatology, Department of Medicine, San Francisco VA Health Care System, San Francisco, CA, USA.
Theodore MiclauDepartment of Orthopaedic Surgery, School of Medicine, Orthopaedic Trauma Institute, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA.
Mary C NakamuraDivision of Rheumatology, Department of Medicine, San Francisco VA Health Care System, San Francisco, CA, USA.
Ralph MarcucioDepartment of Orthopaedic Surgery, School of Medicine, Orthopaedic Trauma Institute, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-0537-818X
San Francisco General Hospital · USSan Francisco VA Health Care System · US

Funding

UCSF Core Center for Musculoskeletal Biology and MedicineP30AR066262 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MAJUMDAR, SHARMILA · 2014 to 2018
$3.0M
Effects of Aging on Macrophages and Bone RegenerationR01AG046282 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARCUCIO, RALPH S, NAKAMURA, MARY C · 2013 to 2016
$784k
NIAMS NIH HHS P30 AR066262NIA NIH HHS R01 AG046282NIA NIH HHS R01AG046282
6 · The paper itself

Abstract

The elderly population suffers from higher rates of complications during fracture healing that result in increased morbidity and mortality. Inflammatory dysregulation is associated with increased age and is a contributing factor to the myriad of age-related diseases. Therefore, we investigated age-related changes to an important cellular regulator of inflammation, the macrophage, and the impact on fracture healing outcomes. We demonstrated that old mice (24 months) have delayed fracture healing with significantly less bone and more cartilage compared to young mice (3 months). The quantity of infiltrating macrophages into the fracture callus was similar in old and young mice. However, RNA-seq analysis demonstrated distinct differences in the transcriptomes of macrophages derived from the fracture callus of old and young mice, with an up-regulation of M1/pro-inflammatory genes in macrophages from old mice as well as dysregulation of other immune-related genes. Preventing infiltration of the fracture site by macrophages in old mice improved healing outcomes, with significantly more bone in the calluses of treated mice compared to age-matched controls. After preventing infiltration by macrophages, the macrophages remaining within the fracture callus were collected and examined via RNA-seq analysis, and their transcriptome resembled macrophages from young calluses. Taken together, infiltrating macrophages from old mice demonstrate detrimental age-related changes, and depleting infiltrating macrophages can improve fracture healing in old mice.

Indexed as

TranscriptomeAge FactorsAminopyridinesAnimalsBony CallusCellular SenescenceFracture HealingFractures, BoneInflammationMacrophagesMiceMice, Inbred C57BLModels, AnimalPyrrolesRNA-SeqTibiaAminopyridinespexidartinibPyrrolesagingfracture healinginflammationmacrophageosteoimmunologyRNA-seq

Identifiers

PMID32096907
PMCPMC7059136
OpenAlexW3006750619

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.