NSUN2 通过 KLF2 的 m5C 甲基化促进大鼠肌腱衍生干细胞的成腱分化

IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING
{"title":"NSUN2 通过 KLF2 的 m5C 甲基化促进大鼠肌腱衍生干细胞的成腱分化","authors":"","doi":"10.1016/j.reth.2024.08.023","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Tendon-derived stem cells (TDSCs) play a critical role in tendon repair. N5-methylcytosine (m5C) is a key regulator of cellular processes such as differentiation. This study aimed to investigate the impact of m5C on TDSC differentiation and the underlying mechanism.</p></div><div><h3>Methods</h3><p>TDSCs were isolated from rats and identified, and a tendon injury rat model was generated. Tenogenic differentiation <em>in vitro</em> was evaluated using Sirius red staining and quantitative real-time polymerase chain reaction, while that <em>in vivo</em> was assessed using immunohistochemistry and hematoxylin‒eosin staining. m5C methylation was analyzed using methylated RNA immunoprecipitation, dual-luciferase reporter assay, and RNA stability assay.</p></div><div><h3>Results</h3><p>The results showed that m5C levels and NSUN2 expression were increased in TDSCs after tenogenic differentiation. Knockdown of NSUN2 inhibited m5C methylation of KLF2 and decreased its stability, which was recognized by YBX1. Moreover, interfering with KLF2 suppressed tenogenic differentiation of TDSCs, which could be abrogated by KLF2 overexpression. Additionally, TDSCs after NSUN2 overexpression contributed to ameliorating tendon injury <em>in vivo</em>. In conclusion, NSUN2 promotes tenogenic differentiation of TDSCs via m5C methylation of KLF2 and accelerates tendon repair.</p></div><div><h3>Conclusions</h3><p>The findings suggest that overexpression of NSUN2 can stimulate the differentiation ability of TDSCs, which can be used in the treatment of tendinopathy.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001585/pdfft?md5=0180a9ed582631d2e1bc71dcb63bdf7d&pid=1-s2.0-S2352320424001585-main.pdf","citationCount":"0","resultStr":"{\"title\":\"NSUN2 facilitates tenogenic differentiation of rat tendon-derived stem cells via m5C methylation of KLF2\",\"authors\":\"\",\"doi\":\"10.1016/j.reth.2024.08.023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>Tendon-derived stem cells (TDSCs) play a critical role in tendon repair. N5-methylcytosine (m5C) is a key regulator of cellular processes such as differentiation. This study aimed to investigate the impact of m5C on TDSC differentiation and the underlying mechanism.</p></div><div><h3>Methods</h3><p>TDSCs were isolated from rats and identified, and a tendon injury rat model was generated. Tenogenic differentiation <em>in vitro</em> was evaluated using Sirius red staining and quantitative real-time polymerase chain reaction, while that <em>in vivo</em> was assessed using immunohistochemistry and hematoxylin‒eosin staining. m5C methylation was analyzed using methylated RNA immunoprecipitation, dual-luciferase reporter assay, and RNA stability assay.</p></div><div><h3>Results</h3><p>The results showed that m5C levels and NSUN2 expression were increased in TDSCs after tenogenic differentiation. Knockdown of NSUN2 inhibited m5C methylation of KLF2 and decreased its stability, which was recognized by YBX1. Moreover, interfering with KLF2 suppressed tenogenic differentiation of TDSCs, which could be abrogated by KLF2 overexpression. Additionally, TDSCs after NSUN2 overexpression contributed to ameliorating tendon injury <em>in vivo</em>. In conclusion, NSUN2 promotes tenogenic differentiation of TDSCs via m5C methylation of KLF2 and accelerates tendon repair.</p></div><div><h3>Conclusions</h3><p>The findings suggest that overexpression of NSUN2 can stimulate the differentiation ability of TDSCs, which can be used in the treatment of tendinopathy.</p></div>\",\"PeriodicalId\":20895,\"journal\":{\"name\":\"Regenerative Therapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2352320424001585/pdfft?md5=0180a9ed582631d2e1bc71dcb63bdf7d&pid=1-s2.0-S2352320424001585-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Regenerative Therapy\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2352320424001585\",\"RegionNum\":3,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Regenerative Therapy","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2352320424001585","RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0

摘要

导言肌腱衍生干细胞(TDSCs)在肌腱修复中发挥着关键作用。N5-甲基胞嘧啶(m5C)是细胞分化等过程的关键调节因子。本研究旨在探讨 m5C 对 TDSC 分化的影响及其内在机制。采用甲基化 RNA 免疫沉淀法、双荧光素酶报告分析法和 RNA 稳定性分析法对 m5C 甲基化进行分析。敲除 NSUN2 可抑制 KLF2 的 m5C 甲基化并降低其稳定性,YBX1 可识别这种甲基化。此外,干扰 KLF2 可抑制 TDSCs 的成腱分化,而过表达 KLF2 则可抑制成腱分化。此外,NSUN2过表达后的TDSCs有助于改善体内肌腱损伤。总之,NSUN2 可通过 KLF2 的 m5C 甲基化促进 TDSCs 的腱源性分化,加速肌腱修复。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
NSUN2 facilitates tenogenic differentiation of rat tendon-derived stem cells via m5C methylation of KLF2

Introduction

Tendon-derived stem cells (TDSCs) play a critical role in tendon repair. N5-methylcytosine (m5C) is a key regulator of cellular processes such as differentiation. This study aimed to investigate the impact of m5C on TDSC differentiation and the underlying mechanism.

Methods

TDSCs were isolated from rats and identified, and a tendon injury rat model was generated. Tenogenic differentiation in vitro was evaluated using Sirius red staining and quantitative real-time polymerase chain reaction, while that in vivo was assessed using immunohistochemistry and hematoxylin‒eosin staining. m5C methylation was analyzed using methylated RNA immunoprecipitation, dual-luciferase reporter assay, and RNA stability assay.

Results

The results showed that m5C levels and NSUN2 expression were increased in TDSCs after tenogenic differentiation. Knockdown of NSUN2 inhibited m5C methylation of KLF2 and decreased its stability, which was recognized by YBX1. Moreover, interfering with KLF2 suppressed tenogenic differentiation of TDSCs, which could be abrogated by KLF2 overexpression. Additionally, TDSCs after NSUN2 overexpression contributed to ameliorating tendon injury in vivo. In conclusion, NSUN2 promotes tenogenic differentiation of TDSCs via m5C methylation of KLF2 and accelerates tendon repair.

Conclusions

The findings suggest that overexpression of NSUN2 can stimulate the differentiation ability of TDSCs, which can be used in the treatment of tendinopathy.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Regenerative Therapy
Regenerative Therapy Engineering-Biomedical Engineering
CiteScore
6.00
自引率
2.30%
发文量
106
审稿时长
49 days
期刊介绍: Regenerative Therapy is the official peer-reviewed online journal of the Japanese Society for Regenerative Medicine. Regenerative Therapy is a multidisciplinary journal that publishes original articles and reviews of basic research, clinical translation, industrial development, and regulatory issues focusing on stem cell biology, tissue engineering, and regenerative medicine.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信