Evidence map›Paper›PMID 31728188›Full record

ArticleBone & joint research2019

Precise immunomodulation of the M1 to M2 macrophage transition enhances mesenchymal stem cell osteogenesis and differs by sex.

Karthik Nathan, Laura Y Lu, Tzuhua Lin, Jukka Pajarinen, Eemeli Jämsen, Jhih-Fong Huang, Monica Romero-Lopez, Masahiro Maruyama, Yusuke Kohno, Zhenyu Yao and 1 more

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

Article in Bone & joint research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
6.7field-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

49 citing papers in PubMed, 86 citations in OpenAlex.

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  12. PeriostinBone research · 2024
    Article
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  15. Black Phosphorus Accelerates Bone Regeneration Based on Immunoregulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    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 2 institutions in 2 countries.

Karthik NathanDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Laura Y LuDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Tzuhua LinDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Jukka PajarinenDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Eemeli JämsenDepartment of Medicine, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland.
Jhih-Fong HuangDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Monica Romero-LopezDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Masahiro MaruyamaDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Yusuke KohnoDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Zhenyu YaoDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Stuart B GoodmanDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA; Department of Bioengineering, Stanford University, Stanford, California, USA.
Stanford University · USHelsinki University Hospital · FI

Funding

Wear Particle Disease and NF-kappa B SignalingR01AR063717 · NIAMS · STANFORD UNIVERSITY · PI GOODMAN, STUART B · 2012 to 2021
$3.5M
Tissue Engineering Approaches for Improved Treatment of Early Stage Osteonecrosis of the HipR01AR072613 · NIAMS · STANFORD UNIVERSITY · PI GOODMAN, STUART B, YANG, YUNZHI · 2018 to 2022
$2.2M
Customized MSCs to Enhance Healing of Bone DefectsR01AR073145 · NIAMS · STANFORD UNIVERSITY · PI GOODMAN, STUART B · 2018 to 2021
$1.4M
NIAMS NIH HHS R01 AR063717NIAMS NIH HHS R01 AR072613NIAMS NIH HHS R01 AR073145
6 · The paper itself

Abstract

objectivesUp to 10% of fractures result in undesirable outcomes, for which female sex is a risk factor. Cellular sex differences have been implicated in these different healing processes. Better understanding of the mechanisms underlying bone healing and sex differences in this process is key to improved clinical outcomes. This study utilized a macrophage-mesenchymal stem cell (MSC) coculture system to determine: 1) the precise timing of proinflammatory (M1) to anti-inflammatory (M2) macrophage transition for optimal bone formation; and 2) how such immunomodulation was affected by male

methodsA primary murine macrophage-MSC coculture system was used to demonstrate the optimal transition time from M1 to M2 (polarized from M1 with interleukin (IL)-4) macrophages to maximize matrix mineralization in male and female MSCs. Outcome variables included Alizarin Red staining, alkaline phosphatase (ALP) activity, and osteocalcin protein secretion.

resultsWe found that 96 hours of M1 phenotype in male cocultures allowed for maximum matrix mineralization

conclusionThese results suggest that: 1) a 72- to 96-hour proinflammatory environment is critical for optimal matrix mineralization; and 2) there are immunological differences in this coculture environment due to sex. Optimizing immunomodulation during fracture healing may enhance and expedite the bone regeneration response. These findings provide insight into precise immunomodulation for enhanced bone healing that is sex-specific.

Indexed as

CocultureMacrophagesMesenchymal stem cellsOsteogenesisSex differences

Identifiers

PMID31728188
PMCPMC6825050
OpenAlexW2981600320

What OpenQuestion holds

Textmetadata
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.