Wei Lin , Zhi Lin , Lizhi Wu , Youmao Zheng , Huifeng Xi
{"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":"Wei Lin , Zhi Lin , Lizhi Wu , Youmao Zheng , Huifeng Xi","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":"26 ","pages":"Pages 792-799"},"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\":\"Wei Lin , Zhi Lin , Lizhi Wu , Youmao Zheng , Huifeng Xi\",\"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\":\"26 \",\"pages\":\"Pages 792-799\"},\"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}
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.
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.
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