Evidence map›Paper›PMID 26881698›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2016

Increased DNA Methylation and Reduced Expression of Transcription Factors in Human Osteoarthritis Cartilage.

Oscar Alvarez-Garcia, Kathleen M Fisch, Nathan E Wineinger, Ryuichiro Akagi, Masahiko Saito, Takahisa Sasho, Andrew I Su, Martin K Lotz

Open access · greenAbstract read
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. 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
6.6field-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, 79 citations in OpenAlex.

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  15. WTAP-mediated mExperimental & molecular medicine · 2024
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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 2 institutions in 2 countries.

Oscar Alvarez-GarciaThe Scripps Research Institute, La Jolla, California.
Kathleen M FischThe Scripps Research Institute, La Jolla, California.
Nathan E WineingerThe Scripps Translational Science Institute, La Jolla, California.
Ryuichiro AkagiThe Scripps Research Institute, La Jolla, California, and Chiba University, Chiba, Japan.
Masahiko SaitoChiba University, Chiba, Japan.
Takahisa SashoChiba University, Chiba, Japan.
Andrew I SuThe Scripps Research Institute, La Jolla, California.
Martin K LotzThe Scripps Research Institute, La Jolla, California.
Scripps Research Institute · USChiba University · JP

Funding

TISSUE ACQUISITION, MORPHOLOGY, AND CELL CULTUREP01AG007996 · NIA · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI SAH, ROBERT L · 1989 to 2016
$26.0M
Scripps Translational Science InstituteUL1TR001114 · NCATS · SCRIPPS RESEARCH INSTITUTE, THE · PI TOPOL, ERIC JEFFREY · 2013 to 2017
$24.0M
Integrative Omics analysis of human cartilage in aging and osteoarthritisR01AG049617 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LOTZ, MARTIN K · 2016 to 2024
$5.6M
NCATS NIH HHS UL1 TR001114NIA NIH HHS P01 AG007996NIA NIH HHS R01 AG049617
6 · The paper itself

Abstract

objectiveTo analyze the methylome of normal and osteoarthritic (OA) knee articular cartilage and to determine the role of DNA methylation in the regulation of gene expression in vitro.

methodsDNA was isolated from human normal (n = 11) and OA (n = 12) knee articular cartilage and analyzed using the Infinium HumanMethylation450 BeadChip array. To integrate methylation and transcription, RNA sequencing was performed on normal and OA cartilage and validated by quantitative polymerase chain reaction. Functional validation was performed in the human TC28 cell line and primary chondrocytes that were treated with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-aza-dC).

resultsDNA methylation profiling revealed 929 differentially methylated sites between normal and OA cartilage, comprising a total of 500 individual genes. Among these, 45 transcription factors that harbored differentially methylated sites were identified. Integrative analysis and subsequent validation showed a subset of 6 transcription factors that were significantly hypermethylated and down-regulated in OA cartilage (ATOH8, MAFF, NCOR2, TBX4, ZBTB16, and ZHX2). Upon 5-aza-dC treatment, TC28 cells showed a significant increase in gene expression for all 6 transcription factors. In primary chondrocytes, ATOH8 and TBX4 were increased after 5-aza-dC treatment.

conclusionOur findings reveal that normal and OA knee articular cartilage have significantly different methylomes. The identification of a subset of epigenetically regulated transcription factors with reduced expression in OA may represent an important mechanism to explain changes in the chondrocyte transcriptome and function during OA pathogenesis.

Indexed as

Cartilage, ArticularCells, CulturedChondrocytesDNA MethylationGene Expression RegulationHumansOsteoarthritisTranscription FactorsTranscription Factors

Identifiers

PMID26881698
PMCPMC4963260
OpenAlexW2282316940

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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.