Evidence map›Paper›PMID 37996046›Full record

ArticleBone2024

A comparison of bone microarchitectural and transcriptomic changes in murine long bones in response to hindlimb unloading and aging.

Steven J Meas, Gabriella M Daire, Michael A Friedman, Rachel DeNapoli, Preetam Ghosh, Joshua N Farr, Henry J Donahue

Open access · greenAbstract read
In one paragraph

Article in Bone, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Multiorgan transcriptomics in mice identifies immunoglobulin heavy constant mu (Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Steven J MeasVirginia Commonwealth University, Richmond, VA 23284, USA. Electronic address: meass2@vcu.edu.
Gabriella M DaireVirginia Commonwealth University, Richmond, VA 23284, USA. Electronic address: dairegm@vcu.edu.
Michael A FriedmanVirginia Commonwealth University, Richmond, VA 23284, USA. Electronic address: mafriedman@vcu.edu.
Rachel DeNapoliVirginia Commonwealth University, Richmond, VA 23284, USA. Electronic address: denapolir@vcu.edu.
Preetam GhoshVirginia Commonwealth University, Richmond, VA 23284, USA. Electronic address: pghosh@vcu.edu.
Joshua N FarrMayo Clinic College of Medicine, Rochester, MN 55905, USA. Electronic address: farr.joshua@mayo.edu.
Henry J DonahueVirginia Commonwealth University, Richmond, VA 23284, USA. Electronic address: hjdonahue@vcu.edu.
Virginia Commonwealth University · USMayo Clinic · US

Funding

GAP JUNCTIONS AND BONE CELL RESPONSE TO PHYSICAL SIGNALSR01AG013087 · NIA · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI DONAHUE, HENRY J · 1994 to 2010
$2.5M
Targeting Cellular Senescence and RAGE in Type 2 DiabetesR01DK128552 · NIDDK · UNIVERSITY OF ARIZONA · PI FARR, JOSHUA NICHOLAS · 2021 to 2025
$2.0M
Gap Junction and Bone Cell Response to Physical SignalsR01AR068132 · NIAMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI DONAHUE, HENRY J · 2014 to 2019
$1.5M
NIAMS NIH HHS R01 AR068132NIA NIH HHS R01 AG013087NIDDK NIH HHS R01 DK128552
6 · The paper itself

Abstract

Age- and disuse-related bone loss both result in decreases in bone mineral density, cortical thickness, and trabecular thickness and connectivity. Disuse induces changes in the balance of bone formation and bone resorption like those seen with aging. There is a need to experimentally compare these two mechanisms at a structural and transcriptomic level to better understand how they may be similar or different. Bone microarchitecture and biomechanical properties were compared between 6- and 22-month-old C57BL/6 J male control mice and 6-month-old mice that were hindlimb unloaded (HLU) for 3 weeks. Epiphyseal trabecular bone was the compartment most affected by HLU and demonstrated an intermediate bone phenotype between age-matched controls and aged controls. RNA extracted from whole-bone marrow-flushed tibiae was sequenced and analyzed. Differential gene expression analysis additionally included 4-month-old male mice unloaded for 3 weeks compared to age-matched controls. Gene ontology analysis demonstrated that there were age-dependent differences in differentially expressed genes in young adult mice. Genes related to downregulation of cellular processes were most affected in 4-month-old mice after disuse whereas those related to mitochondrial function were most affected in 6-month-old mice. Cell-cycle transition was downregulated with aging. A publicly available dataset (GSE169292) from 3-month female C57BL/6 N mice unloaded for 7 days was included in ingenuity pathway analysis (IPA) with the other datasets. IPA was used to identify the leading canonical pathways and upstream regulators in each HLU age group. IPA identified "Senescence Pathway" as the second leading canonical pathway enriched in mice exposed to HLU. HLU induced activation of the senescence pathway in 3-month and 4-month-old mice but inhibited it in 6-month-old mice. In conclusion, we demonstrate that hindlimb unloading and aging initiate similar changes in bone microarchitecture and gene expression. However, aging is responsible for more significant transcriptome and tissue-level changes compared to hindlimb unloading.

Indexed as

Hindlimb SuspensionTranscriptomeAgingAnimalsEpiphysesFemaleGene Expression ProfilingMaleMiceMice, Inbred C57BLAgingDisuseHindlimb unloadingSenescenceTranscriptomics

Identifiers

PMID37996046
PMCPMC11651238
OpenAlexW4388845511

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.