SIRT1 regulates differentiation of mesenchymal stem cells by deacetylating β-catenin
Author(s)
Simic, Petra
Zainabadi, Kayvan
Sykes, David B.
Saez, Borja
Lotinun, Sutada
Baron, Roland
Scadden, David
Schipani, Ernestina
Bell, Eric L.
Guarente, Leonard Pershing
Date Issued
January 2013
Journal
EMBO Molecular Medicine
Publisher
Wiley Blackwell
Citation
Simic, Petra, Kayvan Zainabadi, Eric Bell, David B. Sykes, Borja Saez, Sutada Lotinun, Roland Baron, David Scadden, Ernestina Schipani, and Leonard Guarente. “SIRT1 regulates differentiation of mesenchymal stem cells by deacetylating β-catenin.” EMBO Molecular Medicine 5, no. 3 (March 30, 2013): 430-440.
Version
Final published version
Abstract
Mesenchymal stem cells (MSCs) are multi‐potent cells that can differentiate into osteoblasts, adipocytes, chondrocytes and myocytes. This potential declines with aging. We investigated whether the sirtuin SIRT1 had a function in MSCs by creating MSC specific SIRT1 knock‐out (MSCKO) mice. Aged MSCKO mice (2.2 years old) showed defects in tissues derived from MSCs; i.e. a reduction in subcutaneous fat, cortical bone thickness and trabecular volume. Young mice showed related but less pronounced effects. MSCs isolated from MSCKO mice showed reduced differentiation towards osteoblasts and chondrocytes in vitro, but no difference in proliferation or apoptosis. Expression of β‐catenin targets important for differentiation was reduced in MSCKO cells. Moreover, while β‐catenin itself (T41A mutant resistant to cytosolic turnover) accumulated in the nuclei of wild‐type MSCs, it was unable to do so in MSCKO cells. However, mutating K49R or K345R in β‐catenin to mimic deacetylation restored nuclear localization and differentiation potential in MSCKO cells. We conclude that SIRT1 deacetylates β‐catenin to promote its accumulation in the nucleus leading to transcription of genes for MSC differentiation.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Paul F. Glenn Center for Biology of Aging Research (Massachusetts Institute of Technology)
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1002/emmm.201201606
