Evidence map›Paper›PMID 38309412›Full record

ArticleBone2024

Controlled mechanical loading affects the osteocyte transcriptome in porcine trabecular bone in situ.

Meghana Machireddy, Alyssa G Oberman, Lucas DeBiase, Melissa Stephens, Jun Li, Laurie E Littlepage, Glen L Niebur

Open access · greenAbstract read
PubMed Full text at PMC Publisher
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 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
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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

7 authors at 3 institutions in 1 country.

Meghana MachireddyTissue Mechanics Laboratory, Bioengineering Graduate Program, University of Notre Dame, IN 46556, USA.
Alyssa G ObermanTissue Mechanics Laboratory, Bioengineering Graduate Program, University of Notre Dame, IN 46556, USA.
Lucas DeBiaseDept. of Aerospace and Mechanical Engineering, University of Notre Dame, IN 46556, USA.
Melissa StephensGenomics and Bioinformatics Core Facility, University of Notre Dame, IN 46556, USA.
Jun LiDept. of Applied Mathematics, Computations, and Statistics, University of Notre Dame, IN 46556, USA.
Laurie E LittlepageDept. of Chemistry and Biochemistry, University of Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, IN 46556, USA.
Glen L NieburTissue Mechanics Laboratory, Bioengineering Graduate Program, University of Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, IN 46556, USA; Dept. of Aerospace and Mechanical Engineering, University of Notre Dame, IN 46556, USA. Electronic address: gniebur@nd.edu.
University of Notre Dame · USApplied Mathematics (United States) · USCancer Research Institute · US

Funding

Spatial correlation of osteocyte gene response to local mechanical strain in bone tissueR21AR075937 · NIAMS · UNIVERSITY OF NOTRE DAME · PI NIEBUR, GLEN L · 2020 to 2021
$351k
NIAMS NIH HHS R21 AR075937
6 · The paper itself

Abstract

introductionOsteocytes modulate bone adaptation in response to mechanical stimuli imparted by the deforming bone tissue in which they are encased by communicating with osteoclasts and osteoblasts as well as other osteocytes in the lacuna-canalicular network through secreted cytokines and chemokines. Understanding the transcriptional response of osteocytes to mechanical stimulation in situ could identify new targets to inhibit bone loss or enhance bone formation in the presence of diseases like osteoporosis or metastatic cancer. We compared the mechanically regulated transcriptional response of osteocytes in trabecular bone following one or three days of controlled mechanical loading.

methodsPorcine trabecular bone explants were cultured in a bioreactor for 48 h and subsequently loaded twice a day for one day or 3 days. RNA was isolated and sequenced, and the Tuxedo suite was used to identify differentially expressed genes and pathway analysis was conducted using Ingenuity Pathway Analysis (IPA).

resultsThere were about 4000 differentially expressed genes following in situ culture relative to fresh bone. One hundred six genes were differentially expressed between the loaded and non-loaded groups following one day of loading compared to 913 genes after 3 d of loading. Only 45 of these were coincident between the two time points, indicating an evolving transcriptome. Clustering and principal component analysis indicated differences between the loaded and non-loaded groups after 3 d of loading. DISCUSSION: With sustained loading, there was a nine-fold increase in the number of differentially expressed genes, suggesting that osteocytes respond to loading through sequential activation of downstream genes in the same pathways. The differentially expressed genes were related to osteoarthritis, osteocyte, and chondrocyte signaling pathways. We noted that NFkB and TNF signaling are affected by early loading and this may drive downstream effects on the mechanobiological response. Moreover, these genes may regulate catabolic effects of mechanical disuse through their actions on pre-osteoclasts in the bone marrow niche.

Indexed as

Cancellous BoneOsteocytesAnimalsBone and BonesOsteoblastsStress, MechanicalSwineTranscriptomeBioreactorMechanobiologyOrgan cultureTrabecular boneTranscriptomics

Identifiers

PMID38309412
PMCPMC10923013
OpenAlexW4391483345

What OpenQuestion holds

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Registered trials

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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.