Evidence map›Paper›PMID 33227437›Full record

ArticleOsteoarthritis and cartilage2021

The combination of mitogenic stimulation and DNA damage induces chondrocyte senescence.

M E Copp, M C Flanders, R Gagliardi, J M Gilbertie, G A Sessions, S Chubinskaya, R F Loeser, L V Schnabel, B O Diekman

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Osteoarthritis and cartilage, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

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  17. In vitro study to identify ligand-independent function of estrogen receptor-α in suppressing DNA damage-induced chondrocyte senescence.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
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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

9 authors at 3 institutions in 1 country.

M E CoppJoint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA; Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA. Electronic address: coppme@live.unc.edu.
M C FlandersThurston Arthritis Research Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; NC State College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA. Electronic address: mflande@ncsu.edu.
R GagliardiNC State College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA. Electronic address: rgaglia@ncsu.edu.
J M GilbertieNC State College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA. Electronic address: jmgilbe2@ncsu.edu.
G A SessionsThurston Arthritis Research Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: garrett_sessions@med.unc.edu.
S ChubinskayaDepartment of Pediatrics, Rush University Medical Center, Chicago, IL, USA. Electronic address: Susanna_Chubinskaya@rush.edu.
R F LoeserThurston Arthritis Research Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Division of Rheumatology, Allergy, and Immunology, University of North Carolina, Chapel Hill, NC, USA. Electronic address: richard_loeser@med.unc.edu.
L V SchnabelThurston Arthritis Research Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; NC State College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA. Electronic address: lvschnab@ncsu.edu.
B O DiekmanJoint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA; Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA. Electronic address: bdiekman@email.unc.edu.
University of North Carolina at Chapel Hill · USNorth Carolina State University · USRush University Medical Center · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Re-Entry Supplement: Investigation of Oral Microbial Enzymes for the Detection and Treatment of Periodontal DiseaseUL1TR002489 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BUSE, JOHN BERNARD, SHAHEEN, NICHOLAS J · 2018 to 2022
$48.6M
Oxidative Stress and the Development of OsteoarthritisR01AG044034 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI RICHARD F LOESER · 2012 to 2026
$5.7M
NCATS NIH HHS UL1 TR002489NCI NIH HHS P30 CA016086NIA NIH HHS R01 AG044034
6 · The paper itself

Abstract

objectiveCellular senescence is a phenotypic state characterized by stable cell-cycle arrest, enhanced lysosomal activity, and the secretion of inflammatory molecules and matrix degrading enzymes. Senescence has been implicated in osteoarthritis (OA) pathophysiology; however, the mechanisms that drive senescence induction in cartilage and other joint tissues are unknown. While numerous physiological signals are capable of initiating senescence, one emerging theme is that damaged cells convert to senescence in response to sustained mitogenic stimulation. The goal of this study was to develop an in vitro articular cartilage explant model to investigate the mechanisms of senescence induction.

designThis study utilized healthy cartilage derived from cadaveric equine stifles and human ankles. Explants were irradiated to initiate DNA damage, and mitogenic stimulation was provided through serum-containing medium and treatment with transforming growth factor β1 and basic fibroblastic growth factor. Readouts of senescence were a quantitative flow cytometry assay to detect senescence-associated β galactosidase activity (SA-β-gal), immunofluorescence for p16 and γH2AX, and qPCR for the expression of inflammatory genes.

resultsHuman cartilage explants required both irradiation and mitogenic stimulation to induce senescence as compared to baseline control conditions (7.16% vs 2.34% SA-β-gal high, p = 0.0007). These conditions also resulted in chondrocyte clusters within explants, a persistent DNA damage response, increased p16, and gene expression changes.

conclusionsTreatment of cartilage explants with mitogenic stimuli in the context of cellular damage reliably induces high levels of SA-β-gal activity and other senescence markers, which provides a physiologically relevant model system to investigate the mechanisms of senescence induction.

Indexed as

AnimalsAnkle Jointbeta-GalactosidaseCartilage, ArticularCellular SenescenceChemokine CCL2ChondrocytesCyclin-Dependent Kinase Inhibitor p16DNA DamageFibroblast Growth Factor 2Gene ExpressionHistonesHorsesHumansInflammationInsulin-Like Growth Factor Binding Protein 3beta-GalactosidaseCDKN2A protein, humanChemokine CCL2Cyclin-Dependent Kinase Inhibitor p16Fibroblast Growth Factor 2GLB1 protein, humanH2AX protein, humanHistonesInsulin-Like Growth Factor Binding Protein 3Interleukin-6Matrix Metalloproteinase 13MitogensTransforming Growth Factor beta1AgingbFGFDNA damageOsteoarthritisSA-β-galTGF- β1

Identifiers

PMID33227437
PMCPMC7925350
OpenAlexW3110124528

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.