Epigallocatechin gallate impels osteogenic differentiation of human BMSCs by targeting the METTL3/SATB2/Wnt/β-catenin axis

IF 1.6 4区医学 Q4 CHEMISTRY, MEDICINAL

Letters in Drug Design & Discovery Pub Date : 2025-03-01 DOI:10.1016/j.lddd.2025.100027

Qiao Ren, Kang Chen, Lin Wang

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引用次数: 2

Abstract

Bone marrow mesenchymal stem cells (BMSCs) are pluripotent cell, and its osteogenic differentiation disorder can lead to osteoporosis and seriously affect the quality of life. Epigallocatechin gallate (EGCG) is a catechin that has not been thoroughly studied on BMSCs. Flow cytometry was used for detecting cell surface antigens to identify BMSCs. Cell viability was measured using cell counting kit-8 (CCK8). Alkaline phosphatase (ALP) and alizarin red s (ARS) staining were employed for analyzing osteogenic differentiation. The expression of related genes was examined by western blot and quantitative real-time PCR (qRT-PCR). For the study of mechanism, ENCORI database, SRAMP database, methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP) and mRNA stability assay were utilized to predict and validate the interactions between the proteins. EGCG enhanced cell viability and osteogenic differentiation of BMSCs. Moreover, special AT-rich sequence-binding protein 2 (SATB2) knockdown reversed the effect of EGCG in BMSCs. Mechanically, methyltransferase 3 (METTL3) mediated the N 6 -methyladenosine (m6A) methylation of SATB2. -Furthermore, EGCG-mediated promotion on BMSCs was weakened with the absence of METTL3. In addition, the deficiency of METTL3 and SATB2 could -abolish the effect of EGCG on Wnt/β-catenin pathway. EGCG induced osteogenic differentiation of BMSCs by affecting the METTL3/SATB2-mediated Wnt/β-catenin pathway.

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表没食子儿茶素没食子酸酯通过靶向METTL3/SATB2/Wnt/β-catenin轴促进人骨髓间充质干细胞成骨分化

骨髓间充质干细胞（BMSCs）是一种多能性细胞，其成骨分化障碍可导致骨质疏松，严重影响生活质量。儿茶素没食子儿茶素没食子酸酯（EGCG）是一种儿茶素，尚未在骨髓间充质干细胞中进行深入研究。采用流式细胞术检测细胞表面抗原，鉴定骨髓间充质干细胞。采用细胞计数试剂盒-8 （CCK8）测定细胞活力。采用碱性磷酸酶（ALP）和茜素红（ARS）染色分析成骨分化。western blot和qRT-PCR检测相关基因的表达。机制研究采用ENCORI数据库、SRAMP数据库、甲基化RNA免疫沉淀（MeRIP）、RNA免疫沉淀（RIP）和mRNA稳定性分析预测和验证蛋白之间的相互作用。EGCG增强骨髓间充质干细胞的细胞活力和成骨分化。此外，特殊的AT-rich sequence-binding protein 2 （SATB2）敲低可以逆转EGCG在骨髓间充质干细胞中的作用。机械地，甲基转移酶3 （METTL3）介导SATB2的n6 -甲基腺苷（m6A）甲基化。-此外，egcg对BMSCs的促进作用随着METTL3的缺失而减弱。此外，METTL3和SATB2的缺乏可以消除EGCG对Wnt/β-catenin通路的作用。EGCG通过影响METTL3/ satb2介导的Wnt/β-catenin通路诱导BMSCs成骨分化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Letters in Drug Design & Discovery 医学-医药化学

CiteScore

1.80

自引率

10.00%

发文量

245

审稿时长

3 months

期刊介绍： Aims & Scope Letters in Drug Design & Discovery publishes letters, mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.