title: Different effects of resveratrol on early and late passage mesenchymal stem cells through β-catenin regulation.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, South Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
authors.forename: Dong Suk
authors.initials: DS
authors.lastname: Yoon
authors.affiliation: Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, South Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
authors.forename: Yoorim
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, South Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
authors.forename: Seong Mi
authors.initials: SM
authors.lastname: Choi
authors.affiliation: Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Kwang Hwan
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, South Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea. Electronic address: ljwos@yuhs.ac.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Lee
mesh_terms: D000328:Adult; D016922:Cellular Senescence / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D013267:Stilbenes; D051176:beta Catenin; D000077185:Resveratrol
keywords: Cellular senescence; Mesenchymal stem cells; Resveratrol; SIRT1; β-catenin