SIRT1 is a positive regulator of the master osteoblast transcription factor, RUNX2
PublisherPublic Library of Science
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AbstractActivation 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. Copyright 2017 Zainabadi et al.
SponsorsThis work was supported by grants from the NIH and The Glenn Foundation for Medical Research to LG.
Core Binding Factor Alpha 1 Subunit--metabolism
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85019720420&doi=10.1371%2fjournal.pone.0178520&partnerID=40&md5=653a6b5d530991412cddfb8581660457; http://hdl.handle.net/10713/11104