SIRT1 is a positive regulator of the master osteoblast transcription factor, RUNX2. Academic Article uri icon

Overview

abstract

  • Activation of SIRT1 has previously been shown to protect mice against osteoporosis through yet ill-defined mechanisms. In this study, we outline a role for SIRT1 as a positive regulator of the master osteoblast transcription factor, RUNX2. We find that ex vivo deletion of sirt1 leads to decreased expression of runx2 downstream targets, but not runx2 itself, along with reduced osteoblast differentiation. Reciprocally, treatment with a SIRT1 agonist promotes osteoblast differentiation, as well as the expression of runx2 downstream targets, in a SIRT1-dependent manner. Biochemical and luciferase reporter assays demonstrate that SIRT1 interacts with and promotes the transactivation potential of RUNX2. Intriguingly, mice treated with the SIRT1 agonist, resveratrol, show similar increases in the expression of RUNX2 targets in their calvaria (bone tissue), validating SIRT1 as a physiologically relevant regulator of RUNX2.

publication date

  • May 25, 2017

Research

keywords

  • Core Binding Factor Alpha 1 Subunit
  • Osteoblasts
  • Transcription Factors

Identity

PubMed Central ID

  • PMC5444833

Scopus Document Identifier

  • 85019720420

Digital Object Identifier (DOI)

  • 10.1210/en.2014-1334

PubMed ID

  • 28542607

Additional Document Info

volume

  • 12

issue

  • 5