Evidence map›Paper›PMID 28798419›Full record

ArticleScientific reports2017

DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes.

Atsushi Takahashi, María C de Andrés, Ko Hashimoto, Eiji Itoi, Miguel Otero, Mary B Goldring, Richard O C Oreffo

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 4% 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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Regulation of Skeletal Development and Maintenance by Runx2 and Sp7.International journal of molecular sciences · 2024
    Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Epigenetics as a Therapeutic Target in Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2023
    Review
  13. Article
  14. Review
  15. Article
  16. Multi-omics molecular biomarkers and database of osteoarthritis.Database : the journal of biological databases and curation · 2022
    Article
  17. Article
  18. Article
  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 3 institutions in 3 countries.

Atsushi TakahashiBone and Joint Research Group, Centre for Human Development Stem Cells and Regeneration, Institute of Developmental Science, University of Southampton Medical School, Southampton, UK.
María C de AndrésBone and Joint Research Group, Centre for Human Development Stem Cells and Regeneration, Institute of Developmental Science, University of Southampton Medical School, Southampton, UK.
Ko HashimotoDepartment of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Japan.
Eiji ItoiDepartment of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Japan.
Miguel OteroHSS Research Institute, Hospital for Special Surgery, and Weill Cornell Medical College, New York, NY, USA.
Mary B GoldringHSS Research Institute, Hospital for Special Surgery, and Weill Cornell Medical College, New York, NY, USA.ORCID 0000-0001-5407-9293
Richard O C OreffoBone and Joint Research Group, Centre for Human Development Stem Cells and Regeneration, Institute of Developmental Science, University of Southampton Medical School, Southampton, UK. roco@soton.ac.uk.ORCID 0000-0001-5995-6726
Hospital for Special Surgery · USTohoku University · JPUniversity of Southampton · GB

Funding

Epigenetic Regulation of MMP-13R21AR054887 · NIAMS · HOSPITAL FOR SPECIAL SURGERY · PI GOLDRING, MARY B · 2007 to 2008
$355k
Biotechnology and Biological Sciences Research Council BB/G010579/1NIAMS NIH HHS R21 AR054887
6 · The paper itself

Abstract

The Runt-related transcription factor 2 (RUNX2) is critical for bone formation as well as chondrocyte maturation. Matrix metalloproteinase (MMP)-13 is a major contributor to cartilage degradation in osteoarthritis (OA). We and others have shown that the abnormal MMP13 gene expression in OA chondrocytes is controlled by changes in the DNA methylation status of specific CpG sites of the proximal promoter, as well as by the actions of different transactivators, including RUNX2. The present study aimed to determine the influence of the methylation status of specific CpG sites in the RUNX2 promoter on RUNX2-driven MMP13 gene expression in OA chondrocytes. We observed a significant correlation between MMP13 mRNA levels and RUNX2 gene expression in human OA chondrocytes. RUNX2 overexpression enhanced MMP13 promoter activity, independent of the MMP13 promoter methylation status. A significant negative correlation was observed between RUNX2 mRNA levels in OA chondrocytes and the percentage methylation of the CpG sites in the RUNX2 P1 promoter. Accordingly, the activity of the wild type RUNX2 promoter was decreased upon methylation treatment in vitro. We conclude that RUNX2 gene transcription is regulated by the methylation status of specific CpG sites in the promoter and may determine RUNX2 availability in OA cartilage for transactivation of genes such as MMP13.

Indexed as

DNA MethylationAgedAged, 80 and overCase-Control StudiesChondrocytesCore Binding Factor Alpha 1 SubunitFemaleHumansMaleMatrix Metalloproteinase 13OsteoarthritisPromoter Regions, GeneticCore Binding Factor Alpha 1 SubunitMatrix Metalloproteinase 13MMP13 protein, humanRUNX2 protein, human

Identifiers

PMID28798419
PMCPMC5552713
OpenAlexW2664211259

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.