Evidence map›Paper›PMID 36564153›Full record

ArticleAnnals of the rheumatic diseases2023

Senescent cell population with ZEB1 transcription factor as its main regulator promotes osteoarthritis in cartilage and meniscus.

Hannah Swahn, Kun Li, Tomas Duffy, Merissa Olmer, Darryl D D'Lima, Tony S Mondala, Padmaja Natarajan, Steven R Head, Martin K Lotz

Open access · greenAbstract read
In one paragraph

Article in Annals of the rheumatic diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
15.5field-weighted citation impact, top 1% 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

82 citing papers in PubMed, 102 citations in OpenAlex.

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  19. European journal of nuclear medicine and molecular imaging · 2026
    Article
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22 more citing papers are in PubMed but not listed here.

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

9 authors at 3 institutions in 1 country.

Hannah SwahnDepartment of Molecular Medicine, Scripps Research, La Jolla, California, USA.
Kun LiDepartment of Molecular Medicine, Scripps Research, La Jolla, California, USA.
Tomas DuffyDepartment of Molecular Medicine, Scripps Research, La Jolla, California, USA.
Merissa OlmerDepartment of Molecular Medicine, Scripps Research, La Jolla, California, USA.
Darryl D D'LimaDepartment of Molecular Medicine, Scripps Research, La Jolla, California, USA.
Tony S MondalaCenter for Computational Biology & Bioinformatics and Genomics Core, Scripps Research, La Jola, California, USA.
Padmaja NatarajanCenter for Computational Biology & Bioinformatics and Genomics Core, Scripps Research, La Jola, California, USA.
Steven R HeadCenter for Computational Biology & Bioinformatics and Genomics Core, Scripps Research, La Jola, California, USA.
Martin K LotzDepartment of Molecular Medicine, Scripps Research, La Jolla, California, USA mlotz@scripps.edu.ORCID 0000-0002-6299-8799
Scripps Institution of Oceanography · USScripps Health · USScripps Research Institute · US

Funding

Integrative Omics analysis of human cartilage in aging and osteoarthritisR01AG049617 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LOTZ, MARTIN K · 2016 to 2024
$5.6M
Skeletal Phenotyping of Heterozygotes from IMPC Embryonic Lethal LinesR01HD098636 · NICHD · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI MAYE, PETER, ROWE, DAVID W. · 2019 to 2023
$2.8M
High resolution 3D mapping of cellular heterogeneity within multiple types of mineralized tissuesU54AR078664 · NIAMS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI ROWE, DAVID W. · 2020 to 2023
$2.5M
NIAMS NIH HHS U54 AR078664NIA NIH HHS R01 AG049617NICHD NIH HHS R01 HD098636
6 · The paper itself

Abstract

objectivesSingle-cell level analysis of articular cartilage and meniscus tissues from human healthy and osteoarthritis (OA) knees.

methodsSingle-cell RNA sequencing (scRNA-seq) analyses were performed on articular cartilage and meniscus tissues from healthy (n=6, n=7) and OA (n=6, n=6) knees. Expression of genes of interest was validated using immunohistochemistry and RNA-seq and function was analysed by gene overexpression and depletion.

resultsscRNA-seq analyses of human knee articular cartilage (70 972 cells) and meniscus (78 017 cells) identified a pathogenic subset that is shared between both tissues. This cell population is expanded in OA and has strong OA and senescence gene signatures. Further, this subset has critical roles in extracellular matrix (ECM) and tenascin signalling and is the dominant sender of signals to all other cartilage and meniscus clusters and a receiver of TGFβ signalling. Fibroblast activating protein (FAP) is also a dysregulated gene in this cluster and promotes ECM degradation. Regulons that are controlled by transcription factor ZEB1 are shared between the pathogenic subset in articular cartilage and meniscus. In meniscus and cartilage cells, FAP and ZEB1 promote expression of genes that contribute to OA pathogenesis, including senescence.

conclusionsThese single-cell studies identified a senescent pathogenic cell cluster that is present in cartilage and meniscus and has FAP and ZEB1 as main regulators which are novel and promising therapeutic targets for OA-associated pathways in both tissues.

Indexed as

Cartilage, ArticularMeniscusOsteoarthritisCellular SenescenceChondrocytesHumansZinc Finger E-box-Binding Homeobox 1ZEB1 protein, humanZinc Finger E-box-Binding Homeobox 1arthritischondrocytesosteoarthritis

Identifiers

PMID36564153
PMCPMC10076001
OpenAlexW4312129859

What OpenQuestion 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 OpenQuestion graph.