Search for


search for




 

Wedelolactone Promotes the Chondrogenic Differentiation of Mesenchymal Stem Cells by Suppressing EZH2
International Journal of Stem Cells
Published online October 31, 2022;  
© 2022 Korean Society for Stem Cell Research.

Wei Qin1, Lin Yang2, Xiaotong Chen3, Shanyu Ye1, Aijun Liu1, Dongfeng Chen1, Kunhua Hu3

1Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
2Traditional Chinese Medicine Innovation Research Center, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China
3Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Correspondence to: Dongfeng Chen
Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, No. 232 Outer Ring East Road, Panyu District, Guangzhou 510006, China
Tel: +86-020-39358233, Fax: +86-020-39358909
E-mail: chen888@gzucm.edu.cn
Kunhua Hu
Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou 510630, China
Tel: +86-020-85253333, Fax: +86-020-85253339
E-mail: hukunh@mail.sysu.edu.cn
Received March 18, 2022; Revised August 25, 2022; Accepted September 1, 2022.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background and Objectives: Osteoarthritis (OA) is a degenerative disease that leads to the progressive destruction of articular cartilage. Current clinical therapeutic strategies are moderately effective at relieving OA-associated pain but cannot induce chondrocyte differentiation or achieve cartilage regeneration. We investigated the ability of wedelolactone, a biologically active natural product that occurs in Eclipta alba (false daisy), to promote chondrogenic differentiation.
Methods and Results: Real-time reverse transcription–polymerase chain reaction, immunohistochemical staining, and immunofluorescence staining assays were used to evaluate the effects of wedelolactone on the chondrogenic differentiation of mesenchymal stem cells (MSCs). RNA sequencing, microRNA (miRNA) sequencing, and isobaric tags for relative and absolute quantitation analyses were performed to explore the mechanism by which wedelolactone promotes the chondrogenic differentiation of MSCs. We found that wedelolactone facilitates the chondrogenic differentiation of human induced pluripotent stem cell-derived MSCs and rat bone-marrow MSCs. Moreover, the forkhead box O (FOXO) signaling pathway was upregulated by wedelolactone during chondrogenic differentiation, and a FOXO1 inhibitor attenuated the effect of wedelolactone on chondrocyte differentiation. We determined that wedelolactone reduces enhancer of zeste homolog 2 (EZH2)-mediated histone H3 lysine 27 trimethylation of the promoter region of FOXO1 to upregulate its transcription. Additionally, we found that wedelolactone represses miR-1271-5p expression, and that miR-1271-5p post-transcriptionally suppresses the expression of FOXO1 that is dependent on the binding of miR-1271-5p to the FOXO1 3’-untranscribed region.
Conclusions: These results indicate that wedelolactone suppresses the activity of EZH2 to facilitate the chondrogenic differentiation of MSCs by activating the FOXO1 signaling pathway. Wedelolactone may therefore improve cartilage regeneration in diseases characterized by inflammatory tissue destruction, such as OA.
Keywords : Wedelolactone, Chondrogenic differentiation, EZH2, FOXO1, miR-1271-5p

May 2023, 16 (2)
Full Text(PDF) Free
Supplementary File

Social Network Service
Services
Cited By Articles
CrossRef (0)