Different effects of resveratrol on early and late passage mesenchymal stem cells through β-catenin regulation
- Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of)
Resveratrol is a sirtuin 1 (SIRT1) activator and can function as an anti-inflammatory and antioxidant factor. In mesenchymal stem cells (MSCs), resveratrol enhances the proliferation and differentiation potential and has an anti-aging effect. However, contradictory effects of resveratrol on MSC cultures have been reported. In this study, we found that resveratrol had different effects on MSC cultures according to their cell passage and SIRT1 expression. Resveratrol enhanced the self-renewal potential and multipotency of early passage MSCs, but accelerated cellular senescence of late passage MSCs. In early passage MSCs expressing SIRT1, resveratrol decreased ERK and GSK-3β phosphorylation, suppressing β-catenin activity. In contrast, in late passage MSCs, which did not express SIRT1, resveratrol increased ERK and GSK-3β phosphorylation, activating β-catenin. We confirmed that SIRT1-deficient early passage MSCs treated with resveratrol lost their self-renewal potential and multipotency, and became senescent due to increased β-catenin activity. Sustained treatment with resveratrol at early passages maintained the self-renewal potential and multipotency of MSCs up to passage 10. Our findings suggest that resveratrol can be effectively applied to early passage MSC cultures, whereas parameters such as cell passage and SIRT1 expression must be taken into consideration before applying resveratrol to late passage MSCs. - Highlights: • Resveratrol enhances self-renewal potential and multipotency of early passage MSCs. • Resveratrol accelerates the cellular senescence of late passage MSCs. • The effects of resveratrol on MSCs are dependent on the presence of SIRT1. • SIRT1 modulates ERK/GSK-3β/β-catenin signaling. • Sustained resveratrol treatment maintains MSC stemness up to P10.
- OSTI ID:
- 22592830
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 467, Issue 4; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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