Evidence map›Paper›PMID 31945456›Full record

ArticleOsteoarthritis and cartilage2020

RNA-seq analysis of chondrocyte transcriptome reveals genetic heterogeneity in LG/J and SM/J murine strains.

X Duan, L Cai, E J Schmidt, J Shen, E D Tycksen, R J O'Keefe, J M Cheverud, M F Rai

Open access · greenAbstract read
In one paragraph

Article in Osteoarthritis and cartilage, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

12 citing papers in PubMed, 14 citations in OpenAlex.

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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

8 authors at 3 institutions in 1 country.

X DuanDepartment of Orthopedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, MO, United States.
L CaiDepartment of Orthopedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, MO, United States.
E J SchmidtSchool of Physician Assistant Medicine, College of Health Sciences, University of Lynchburg, Lynchburg, VA, United States.
J ShenDepartment of Orthopedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, MO, United States.
E D TycksenGenome Technology Access Center, Washington University School of Medicine, St. Louis, MO, 63110, United States.
R J O'KeefeDepartment of Orthopedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, MO, United States.
J M CheverudDepartment of Biology, Loyola University, Chicago, IL, United States.
M F RaiDepartment of Orthopedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, MO, United States; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, United States. Electronic address: rai.m@wustl.edu.
Washington University in St. Louis · USLoyola University Chicago · USUniversity of Lynchburg · US

Funding

Resource Based Center for Musculoskeletal Biology and Medicine (Overall Application)P30AR074992 · NIAMS · WASHINGTON UNIVERSITY · PI MATTHEW J SILVA · 2019 to 2026
$6.8M
Skeletal Disorders Training ProgramT32AR060719 · NIAMS · WASHINGTON UNIVERSITY · PI Roberto Civitelli · 2011 to 2026
$4.6M
Genetic and Molecular Insights into Cartilage Regeneration, Primary and Posttraumatic OsteoarthritisR00AR064837 · NIAMS · WASHINGTON UNIVERSITY · PI RAI, MUHAMMAD FAROOQ · 2017 to 2019
$747k
NIAMS NIH HHS P30 AR074992NIAMS NIH HHS R00 AR064837NIAMS NIH HHS T32 AR060719
6 · The paper itself

Abstract

objectiveTo investigate the transcriptomic differences in chondrocytes obtained from LG/J (large, healer) and SM/J (small, non-healer) murine strains in an attempt to discern the molecular pathways implicated in cartilage regeneration and susceptibility to osteoarthritis (OA).

designWe performed RNA-sequencing on chondrocytes derived from LG/J (n = 16) and SM/J (n = 16) mice. We validated the expression of candidate genes and compared single nucleotide polymorphisms (SNPs) between the two mouse strains. We also examined gene expression of positional candidates for ear pinna regeneration and long bone length quantitative trait loci (QTLs) that display differences in cartilaginous expression.

resultsWe observed a distinct genetic heterogeneity between cells derived from LG/J and SM/J mouse strains. We found that gene ontologies representing cell development, cartilage condensation, and regulation of cell differentiation were enriched in LG/J chondrocytes. In contrast, gene ontologies enriched in the SM/J chondrocytes were mainly related to inflammation and degeneration. Moreover, SNP analysis revealed that multiple validated genes vary in sequence between LG/J and SM/J in coding and highly conserved noncoding regions. Finally, we showed that most QTLs have 20-30% of their positional candidates displaying differential expression between the two mouse strains.

conclusionsWhile the enrichment of pathways related to cell differentiation, cartilage development and cartilage condensation infers superior healing potential of LG/J strain, the enrichment of pathways related to cytokine production, immune cell activation and inflammation entails greater susceptibility of SM/J strain to OA. These data provide novel insights into chondrocyte transcriptome and aid in identification of the quantitative trait genes and molecular differences underlying the phenotypic differences associated with individual QTLs.

Indexed as

AnimalsCarbonic Anhydrase IICartilageCartilage, ArticularChondrocytesEar AuricleEar CartilageGene Expression ProfilingGenetic Predisposition to DiseaseMiceMice, Inbred StrainsOsteoarthritisPolymorphism, Single NucleotideQuantitative Trait LociReal-Time Polymerase Chain ReactionReceptors, Tumor Necrosis FactorCarbonic Anhydrase IIReceptors, Tumor Necrosis FactorTnfrsf23 protein, mouseCar2Cartilage repairOsteoarthritisQuantitative trait locusSingle nucleotide polymorphismTnfrsf23

Identifiers

PMID31945456
PMCPMC7108965
OpenAlexW3000654981

What Socratic holds

Textmetadata
LicenceTDM
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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 Socratic graph.