SIRT1 is a positive regulator of in vivo bone mass and a therapeutic target for osteoporosis
Name
journal.pone.0185236.pdf
Size
1.91 MB
Format
Adobe PDF
Checksum (MD5)
482ea507bd50a675c496d8d72cce69e3
Author(s)
Zainabadi, Kayvan
Liu, Cassie J
Caldwell, Alison L. M.
Guarente, Leonard Pershing
Date Issued
September 2017
Journal
PLOS ONE
Publisher
Public Library of Science (PLoS)
Citation
Zainabadi, Kayvan et al. “SIRT1 Is a Positive Regulator of in Vivo Bone Mass and a Therapeutic Target for Osteoporosis.” Edited by Jung-Eun Kim. PLOS ONE 12, 9 (September 2017): e0185236 © 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. Overexpression or pharmacological activation of SIRT1 has been shown to extend the lifespan of mice and protect against aging-related diseases. Here we show that pharmacological activation of SIRT1 protects in two models of osteoporosis. Ovariectomized female mice and aged male mice, models for post-menopausal and aging-related osteoporosis, respectively, show significant improvements in bone mass upon treatment with SIRT1 agonist, SRT1720. Further, we find that calorie restriction (CR) results in a two-fold upregulation of sirt1 mRNA expression in bone tissue that is associated with increased bone mass in CR mice. Reciprocally, SIRT1 whole-body knockout (KO) mice, as well as osteoblast and osteoclast specific KOs, show a low bone mass phenotype; though double knockout mice (containing SIRT1 deleted in both osteoblasts and osteoclasts) do not show a more severe phenotype. Altogether, these findings provide strong evidence that SIRT1 is a positive regulator of bone mass and a promising target for the development of novel therapeutics for osteoporosis.
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
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1371/JOURNAL.PONE.0185236
