Evidence map›Paper›PMID 28627522›Full record

ArticleNature communications2017

DOT1L safeguards cartilage homeostasis and protects against osteoarthritis.

Silvia Monteagudo, Frederique M F Cornelis, Carolina Aznar-Lopez, Ploi Yibmantasiri, Laura-An Guns, Peter Carmeliet, Frédéric Cailotto, Rik J Lories

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

81 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Mechanoepigenetics in musculoskeletal disease.Osteoarthritis and cartilage · 2026
    Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Review

21 more citing papers are in PubMed but not listed here.

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

8 authors.

Silvia MonteagudoLaboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven 3000, Belgium.
Frederique M F CornelisLaboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven 3000, Belgium.
Carolina Aznar-LopezLaboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven 3000, Belgium.
Ploi YibmantasiriLaboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven 3000, Belgium.
Laura-An GunsLaboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven 3000, Belgium.
Peter CarmelietLaboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, Leuven 3000, Belgium.
Frédéric CailottoLaboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven 3000, Belgium.
Rik J LoriesLaboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven 3000, Belgium.ORCID 0000-0002-5986-3092

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteoarthritis is the most prevalent and crippling joint disease, and lacks curative treatment, as the underlying molecular basis is unclear. Here, we show that DOT1L, an enzyme involved in histone methylation, is a master protector of cartilage health. Loss of DOT1L disrupts the molecular signature of healthy chondrocytes in vitro and causes osteoarthritis in mice. Mechanistically, the protective function of DOT1L is attributable to inhibition of Wnt signalling, a pathway that when hyper-activated can lead to joint disease. Unexpectedly, DOT1L suppresses Wnt signalling by inhibiting the activity of sirtuin-1 (SIRT1), an important regulator of gene transcription. Inhibition of SIRT1 protects against osteoarthritis triggered by loss of DOT1L activity. Modulating the DOT1L network might therefore be a therapeutic approach to protect the cartilage against osteoarthritis.

Indexed as

AnimalsBenzimidazolesCartilageCells, CulturedChondrocytesFemaleGene Expression RegulationHistone-Lysine N-MethyltransferaseHomeostasisMaleMethylationMethyltransferasesMice, Inbred C57BLMice, KnockoutOsteoarthritisSirtuin 1BenzimidazolesDOT1L protein, humanDot1l protein, mouseEPZ-5676Histone-Lysine N-MethyltransferaseMethyltransferasesSIRT1 protein, humanSirtuin 1

Identifiers

PMID28627522
PMCPMC5481839

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.