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Resveratrol mediated modulation of Sirt-1/Runx2 promotes osteogenic differentiation of mesenchymal stem cells: potential role of Runx2 deacetylation.

Shakibaei, M, Shayan, P, Busch, F, Aldinger, C, Buhrmann, C, Lueders, C and Mobasheri, A (2012) Resveratrol mediated modulation of Sirt-1/Runx2 promotes osteogenic differentiation of mesenchymal stem cells: potential role of Runx2 deacetylation. PLoS One, 7 (4).

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Abstract

OBJECTIVE: Osteogenic repair in response to bone injury is characterized by activation and differentiation of mesenchymal stem cells (MSCs) to osteoblasts. This study determined whether activation of Sirt-1 (a NAD(+)-dependent histone deacetylase) by the phytoestrogen resveratrol affects osteogenic differentiation. METHODS: Monolayer and high-density cultures of MSCs and pre-osteoblastic cells were treated with an osteogenic induction medium with/without the Sirt-1 inhibitor nicotinamide or/and resveratrol in a concentration dependent manner. RESULTS: MSCs and pre-osteoblastic cells differentiated to osteoblasts when exposed to osteogenic-induction medium. The osteogenic response was blocked by nicotinamide, resulting in adipogenic differentiation and expression of the adipose transcription regulator PPAR-γ (peroxisome proliferator-activated receptor). However, in nicotinamide-treated cultures, pre-treatment with resveratrol significantly enhanced osteogenesis by increasing expression of Runx2 (bone specific transcription factor) and decreasing expression of PPAR-γ. Activation of Sirt-1 by resveratrol in MSCs increased its binding to PPAR-γ and repressed PPAR-γ activity by involving its cofactor NCoR (nuclear receptor co-repressor). The modulatory effects of resveratrol on nicotinamide-induced expression of PPAR-γ and its cofactor NCoR were found to be mediated, at least in part, by Sirt-1/Runx2 association and deacetylation of Runx2. Finally, knockdown of Sirt-1 by using antisense oligonucleotides downregulated the expression of Sirt-1 protein and abolished the inhibitory effects of resveratrol, namely nicotinamide-induced Sirt-1 suppression and Runx2 acetylation, suggesting that the acetylated content of Runx2 is related to downregulated Sirt-1 expression. CONCLUSION: These data support a critical role for Runx2 acetylation/deacetylation during osteogenic differentiation in MSCs in vitro. (242 words in abstract).

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Veterinary Medicine
Authors :
AuthorsEmailORCID
Shakibaei, MUNSPECIFIEDUNSPECIFIED
Shayan, PUNSPECIFIEDUNSPECIFIED
Busch, FUNSPECIFIEDUNSPECIFIED
Aldinger, CUNSPECIFIEDUNSPECIFIED
Buhrmann, CUNSPECIFIEDUNSPECIFIED
Lueders, CUNSPECIFIEDUNSPECIFIED
Mobasheri, AUNSPECIFIEDUNSPECIFIED
Date : 23 April 2012
Identification Number : 10.1371/journal.pone.0035712
Uncontrolled Keywords : Acetylation, Animals, Anti-Inflammatory Agents, Non-Steroidal, Cell Differentiation, Core Binding Factor Alpha 1 Subunit, Down-Regulation, Mesenchymal Stromal Cells, Mice, Niacinamide, Nuclear Receptor Co-Repressor 1, Oligonucleotides, Antisense, Osteogenesis, PPAR gamma, Sirtuin 1, Stilbenes
Related URLs :
Additional Information : Copyright: 2012 Shakibaei et al. 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.
Depositing User : Symplectic Elements
Date Deposited : 23 Dec 2015 12:50
Last Modified : 23 Dec 2015 12:50
URI: http://epubs.surrey.ac.uk/id/eprint/809548

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