Evidence map›Paper›PMID 27956552›Full record

ArticleThe Journal of biological chemistry2017

Cytokine-induced MMP13 Expression in Human Chondrocytes Is Dependent on Activating Transcription Factor 3 (ATF3) Regulation.

Chun Ming Chan, Christopher D Macdonald, Gary J Litherland, David J Wilkinson, Andrew Skelton, G Nicholas Europe-Finner, Andrew D Rowan

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
6.3field-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

44 citing papers in PubMed, 73 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. The multifaceted roles of E3 ubiquitin ligases in osteoarthritis.Frontiers in cell and developmental biology · 2025
    Review
  9. Article
  10. The Oral Administration ofCurrent issues in molecular biology · 2024
    Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Characterization of Chromatin Accessibility in Fetal Bovine Chondrocytes.Animals : an open access journal from MDPI · 2023
    Article
  17. Article
  18. Review
  19. Article
  20. Article
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

7 authors at 1 institution in 1 country.

Chun Ming ChanFrom the Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle-upon-Tyne NE2 4HH, United Kingdom.
Christopher D MacdonaldFrom the Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle-upon-Tyne NE2 4HH, United Kingdom.
Gary J LitherlandFrom the Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle-upon-Tyne NE2 4HH, United Kingdom.
David J WilkinsonFrom the Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle-upon-Tyne NE2 4HH, United Kingdom.
Andrew SkeltonFrom the Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle-upon-Tyne NE2 4HH, United Kingdom.
G Nicholas Europe-FinnerFrom the Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle-upon-Tyne NE2 4HH, United Kingdom.
Andrew D RowanFrom the Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle-upon-Tyne NE2 4HH, United Kingdom. Electronic address: drew.rowan@ncl.ac.uk.
Newcastle University · GB

Funding

Arthritis Research UK 18726Versus Arthritis 19485Versus Arthritis 20199
6 · The paper itself

Abstract

Irreversible breakdown of cartilage extracellular matrix (ECM) by the collagenase matrix metalloproteinase 13 (MMP13) represents a key event in osteoarthritis (OA) progression. Although inflammation is most commonly associated with inflammatory joint diseases, it also occurs in OA and is thus relevant to the prevalent tissue destruction. Here, inflammation generates a cFOS AP-1 early response that indirectly affects MMP13 gene expression. To ascertain a more direct effect on prolonged MMP13 production we examined the potential molecular events occurring between the rapid, transient expression of cFOS and the subsequent MMP13 induction. Importantly, we show MMP13 mRNA expression is mirrored by nascent hnRNA transcription. Employing ChIP assays, cFOS recruitment to the MMP13 promoter occurs at an early stage prior to gene transcription and that recruitment of transcriptional initiation markers also correlated with MMP13 expression. Moreover, protein synthesis inhibition following early FOS expression resulted in a significant decrease in MMP13 expression thus indicating a role for different regulatory factors modulating expression of the gene. Subsequent mRNA transcriptome analyses highlighted several genes induced soon after FOS that could contribute to MMP13 expression. Specific small interfering RNA-mediated silencing highlighted that ATF3 was as highly selective for MMP13 as cFOS. Moreover, ATF3 expression was AP-1(cFOS/cJUN)-dependent and expression levels were maintained after the early transient cFOS response. Furthermore, ATF3 bound the proximal MMP13 AP-1 motif in stimulated chondrocytes at time points that no longer supported binding of FOS Consequently, these findings support roles for both cFOS (indirect) and ATF3 (direct) in effecting MMP13 transcription in human chondrocytes.

Indexed as

Activating Transcription Factor 3Cells, CulturedChondrocytesGene Expression Regulation, EnzymologicHumansMatrix Metalloproteinase 13Proto-Oncogene Proteins c-fosProto-Oncogene Proteins c-junResponse ElementsTranscription Factor AP-1TranscriptomeActivating Transcription Factor 3ATF3 protein, humanMatrix Metalloproteinase 13MMP13 protein, humanProto-Oncogene Proteins c-fosProto-Oncogene Proteins c-junTranscription Factor AP-1AP1 transcription factor (AP-1)arthritiscell signalingchondrocyteinflammationmatrix metalloproteinase (MMP)

Identifiers

PMID27956552
PMCPMC5290940
OpenAlexW2563682843

What Socratic holds

Textmetadata
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 Socratic graph.