DOT1L safeguards cartilage homeostasis and protects against osteoarthritis - Université de Lorraine Access content directly
Journal Articles Nature Communications Year : 2017

DOT1L safeguards cartilage homeostasis and protects against osteoarthritis

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.
Fichier principal
Vignette du fichier
ncomms15889.pdf (2.17 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Loading...

Dates and versions

hal-01704515 , version 1 (15-02-2018)

Identifiers

Cite

Silvia Monteagudo, Frederique Cornelis, Carolina Aznar-Lopez, Ploi Yibmantasiri, Laura-An Guns, et al.. DOT1L safeguards cartilage homeostasis and protects against osteoarthritis. Nature Communications, 2017, 8, pp.15889. ⟨10.1038/ncomms15889⟩. ⟨hal-01704515⟩
192 View
99 Download

Altmetric

Share

Gmail Facebook X LinkedIn More