Evidence map›Paper›PMID 19144181›Full record

ArticleArthritis research & therapy2009

Egr-1 inhibits the expression of extracellular matrix genes in chondrocytes by TNFalpha-induced MEK/ERK signalling.

Jason S Rockel, Suzanne M Bernier, Andrew Leask

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.2field-weighted citation impact, top 9% 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

35 citing papers in PubMed, 51 citations in OpenAlex.

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  11. Epigenetic Therapies for Osteoarthritis.Trends in pharmacological sciences · 2020
    Review
  12. Histomorphology and immunohistochemical patterns in degenerative disc disease and clinical-radiological correlations: a prospective study.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2020
    Observational
  13. Review
  14. Dual Role of Chondrocytes in Rheumatoid Arthritis: The Chicken and the Egg.International journal of molecular sciences · 2020
    Review
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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

3 authors at 2 institutions in 1 country.

Jason S RockelCanadian Institutes of Health Research Group in Skeletal Development and Remodeling, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario N6A5C1, Canada. jsrockel@uwo.ca
Suzanne M Bernier
Andrew Leask
Canadian Institutes of Health Research · CAWestern University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionTNFalpha is increased in the synovial fluid of patients with rheumatoid arthritis and osteoarthritis. TNFalpha activates mitogen-activated kinase kinase (MEK)/extracellular regulated kinase (ERK) in chondrocytes; however, the overall functional relevance of MEK/ERK to TNFalpha-regulated gene expression in chondrocytes is unknown.

methodsChondrocytes were treated with TNFalpha with or without the MEK1/2 inhibitor U0126 for 24 hours. Microarray analysis and real-time PCR analyses were used to identify genes regulated by TNFalpha in a MEK1/2-dependent fashion. Promoter/reporter, immunoblot, and electrophoretic mobility shift assays were used to identify transcription factors whose activity in response to TNFalpha was MEK1/2 dependent. Decoy oligodeoxynucleotides bearing consensus transcription factor binding sites were introduced into chondrocytes to determine the functionality of our results.

resultsApproximately 20% of the genes regulated by TNFalpha in chondrocytes were sensitive to U0126. Transcript regulation of the cartilage-selective matrix genes Col2a1, Agc1 and Hapln1, and of the matrix metalloproteinase genes Mmp-12 and Mmp-9, were U0126 sensitive--whereas regulation of the inflammatory gene macrophage Csf-1 was U0126 insensitive. TNFalpha-induced regulation of Sox9 and NFkappaB activity was also U0126 insensitive. Conversely, TNFalpha-increased early growth response 1 (Egr-1) DNA binding was U0126 sensitive. Transfection of chondrocytes with cognate Egr-1 oligodeoxynucleotides attenuated the ability of TNFalpha to suppress Col2a1, Agc1 or Hapln1 mRNA expression.

conclusionsOur results suggest that MEK/ERK and Egr1 are required for TNFalpha-regulated catabolic and anabolic genes of the cartilage extracellular matrix, and hence may represent potential targets for drug intervention in osteoarthritis or rheumatoid arthritis.

Indexed as

Gene Expression RegulationAggrecansAnimalsBlotting, WesternCartilageCells, CulturedChondrocytesCollagen Type IIEarly Growth Response Protein 1Electrophoretic Mobility Shift AssayEnzyme InhibitorsExtracellular MatrixExtracellular Matrix ProteinsGene ExpressionMAP Kinase Signaling SystemOligonucleotide Array Sequence AnalysisAcan protein, ratAggrecansCOL2A1 protein, ratCollagen Type IIEarly Growth Response Protein 1Egr1 protein, ratEnzyme InhibitorsExtracellular Matrix ProteinsProteoglycan Link ProteinProteoglycansTumor Necrosis Factor-alpha

Identifiers

PMID19144181
PMCPMC2688239
OpenAlexW2067411650

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.