Evidence map›Paper›PMID 37828576›Full record

ArticleArthritis research & therapy2023

Synergistic roles of CBX4 chromo and SIM domains in regulating senescence of primary human osteoarthritic chondrocytes.

Yu-Hsiu Chen, Xin Zhang, David Attarian, Virginia Byers Kraus

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 26% 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

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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

2 citing papers in PubMed, 3 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

4 authors at 2 institutions in 2 countries.

Yu-Hsiu ChenDuke Molecular Physiology Institute, Duke University, 300 N Duke St, Durham, NC, 27701, USA.
Xin ZhangDuke Molecular Physiology Institute, Duke University, 300 N Duke St, Durham, NC, 27701, USA.
David AttarianDepartment of Orthopaedic Surgery, Duke University, Durham, NC, USA.
Virginia Byers KrausDuke Molecular Physiology Institute, Duke University, 300 N Duke St, Durham, NC, 27701, USA. vbk@duke.edu.
Duke University · USDuke University Hospital · US

Funding

Resource Core 3 - Metabolomics CoreP30AG028716 · NIA · DUKE UNIVERSITY · PI CATHLEEN S COLON-EMERIC, Susan Nicole Hastings · 2006 to 2026
$24.6M
Extracellular Vesicle Analyses to Develop Aging and Resilience BiomarkersR01AG070146 · NIA · DUKE UNIVERSITY · PI KRAUS, VIRGINIA B · 2021 to 2025
$3.1M
NIA NIH HHS P30 AG028716NIA NIH HHS R01 AG070146NIH HHS P30-AG028716NIH HHS R01AG070146
6 · The paper itself

Abstract

backgroundCellular senescence is a critical factor contributing to osteoarthritis (OA). Overexpression of chromobox homolog 4 (CBX4) in a mouse system was demonstrated to alleviate post-traumatic osteoarthritis (PTOA) by reducing cellular senescence. Additionally, replicative cellular senescence of WI-38 fibroblasts can be attenuated by CBX4. However, the mechanisms underlying this senomorphic function of CBX4 are not fully understood. In this study, we aimed to investigate the role of CBX4 in cellular senescence in human primary osteoarthritic chondrocytes and to identify the functional domains of CBX4 necessary for its function in modulating senescence.

methodsChondrocytes, isolated from 6 individuals undergoing total knee replacement for OA, were transduced with wild-type CBX4, mutant CBX4, and control lentiviral constructs. Senescence-related phenotypic outcomes included the following: multiple flow cytometry-measured markers (p16

resultsCompared with control, CBX4 overexpression in OA chondrocytes decreased DPP4 expression and SASP secretion and increased chondrocyte proliferation confirming CBX4 senomorphic effects on primary human chondrocytes. Point mutations of the chromodomain domain (CDM, involved in chromatin modification) alone were sufficient to partially block the senomorphic activity of CBX4 (p16

conclusionsCBX4 has a senomorphic effect on human osteoarthritic chondrocytes. CDM is critical for CBX4-mediated regulation of senescence. The SIMs are supportive but not indispensable for CBX4 senomorphic function while the C-box is dispensable.

Indexed as

ChondrocytesOsteoarthritisAnimalsBiomarkersCellular SenescenceCyclin-Dependent Kinase Inhibitor p16Dipeptidyl Peptidase 4HumansInterleukin-8LigasesMicePolycomb-Group ProteinsSenotherapeuticsTumor Necrosis Factor-alphaBiomarkersCBX4 protein, humanCyclin-Dependent Kinase Inhibitor p16Dipeptidyl Peptidase 4Interleukin-8LigasesPolycomb-Group ProteinsSenotherapeuticsTumor Necrosis Factor-alphaCBX4Cellular senescenceDPP4OsteoarthritisSenomorphic

Identifiers

PMID37828576
PMCPMC10568837
OpenAlexW4387595211

What OpenQuestion holds

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LicenceCC BY
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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.