SIRT1 is a positive regulator of the master osteoblast transcription factor, RUNX2
Name
journal.pone.0178520.pdf
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5.1 MB
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Adobe PDF
Checksum (MD5)
38ea21ce02d18220e6b070722960b3ce
Author(s)
Zainabadi, Kayvan
Liu, Cassie J
Guarente, Leonard Pershing
Date Issued
May 2017
Journal
PLOS ONE
Publisher
Public Library of Science
Citation
Zainabadi, Kayvan et al. “SIRT1 Is a Positive Regulator of the Master Osteoblast Transcription Factor, RUNX2.” Edited by Jung-Eun Kim. PLOS ONE 12, 5 (May 2017): e0178520 © 2017 Zainabadi et al
Version
Final published version
Abstract
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1371/JOURNAL.PONE.0178520
