METTL3 mediated ferroptosis in chondrocytes and promoted pain in KOA via HMGB1 m6A modification

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Tianchi Bao, Taiyang Liao, Xuefeng Cai, Binjie Lu, Gaole Dai, Shuai Pei, Yunqing Zhang, Yuwei Li, Bo Xu
{"title":"METTL3 mediated ferroptosis in chondrocytes and promoted pain in KOA via HMGB1 m6A modification","authors":"Tianchi Bao,&nbsp;Taiyang Liao,&nbsp;Xuefeng Cai,&nbsp;Binjie Lu,&nbsp;Gaole Dai,&nbsp;Shuai Pei,&nbsp;Yunqing Zhang,&nbsp;Yuwei Li,&nbsp;Bo Xu","doi":"10.1002/cbin.12229","DOIUrl":null,"url":null,"abstract":"<p>Methyltransferase-like 3 (METTL3) plays a role in the development of knee osteoarthritis (KOA). However, the mechanism underlying the role of METTL3 in KOA is unclear. This work investigated the effects of MELLT3 on ferroptosis and pain relief in in vitro and in vivo KOA models. Chondrocytes were treated with 10 ng/mL interleukin-1β (IL-1β) or 5 μM Erastin (ferroptosis inducer). IL-1β or Erastin treatment inhibited cell viability and glutathione levels; increased Fe<sup>2+</sup>, lipid reactive oxygen species and malondialdehyde production; and decreased glutathione peroxidase 4, ferritin light chain and solute carrier family 7 member 11 levels. The overexpression of METTL3 facilitated the N6-methyladenosine methylation of high mobility group box 1 (HMGB1). HMGB1 overexpression reversed the effect of sh-METTL3 on IL-1β-treated chondrocytes. A KOA rat model was established by the injection of monosodium iodoacetate into the joints and successful model establishment was confirmed by haematoxylin and eosin staining and Safranin O/Fast Green staining. METTL3 depletion alleviated cartilage damage, the inflammatory response, ferroptosis and knee pain in KOA model rats, and these effects were reversed by the addition of HMGB1. In conclusion, METTL3 depletion inhibited ferroptosis and the inflammatory response, and ameliorated cartilage damage and knee pain during KOA progression by regulating HMGB1.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"48 11","pages":"1755-1765"},"PeriodicalIF":3.3000,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Biology International","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cbin.12229","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Methyltransferase-like 3 (METTL3) plays a role in the development of knee osteoarthritis (KOA). However, the mechanism underlying the role of METTL3 in KOA is unclear. This work investigated the effects of MELLT3 on ferroptosis and pain relief in in vitro and in vivo KOA models. Chondrocytes were treated with 10 ng/mL interleukin-1β (IL-1β) or 5 μM Erastin (ferroptosis inducer). IL-1β or Erastin treatment inhibited cell viability and glutathione levels; increased Fe2+, lipid reactive oxygen species and malondialdehyde production; and decreased glutathione peroxidase 4, ferritin light chain and solute carrier family 7 member 11 levels. The overexpression of METTL3 facilitated the N6-methyladenosine methylation of high mobility group box 1 (HMGB1). HMGB1 overexpression reversed the effect of sh-METTL3 on IL-1β-treated chondrocytes. A KOA rat model was established by the injection of monosodium iodoacetate into the joints and successful model establishment was confirmed by haematoxylin and eosin staining and Safranin O/Fast Green staining. METTL3 depletion alleviated cartilage damage, the inflammatory response, ferroptosis and knee pain in KOA model rats, and these effects were reversed by the addition of HMGB1. In conclusion, METTL3 depletion inhibited ferroptosis and the inflammatory response, and ameliorated cartilage damage and knee pain during KOA progression by regulating HMGB1.

METTL3 通过 HMGB1 m6A 修饰介导软骨细胞的铁变态反应并促进 KOA 的疼痛。
甲基转移酶样 3(METTL3)在膝关节骨性关节炎(KOA)的发病过程中发挥着作用。然而,METTL3在KOA中发挥作用的机制尚不清楚。这项工作研究了MELLT3在体外和体内KOA模型中对铁蛋白沉积和疼痛缓解的影响。用 10 ng/mL 白细胞介素-1β(IL-1β)或 5 μM Erastin(铁凋亡诱导剂)处理软骨细胞。IL-1β 或 Erastin 处理抑制了细胞活力和谷胱甘肽水平;增加了 Fe2+、脂质活性氧和丙二醛的生成;降低了谷胱甘肽过氧化物酶 4、铁蛋白轻链和溶质运载家族 7 成员 11 的水平。METTL3 的过表达促进了高迁移率基团框 1(HMGB1)的 N6-甲基腺苷甲基化。HMGB1的过表达逆转了sh-METTL3对IL-1β处理的软骨细胞的影响。通过向关节注射碘乙酸钠建立了 KOA 大鼠模型,并通过血红素和伊红染色以及 Safranin O/Fast Green 染色证实了模型的成功建立。消耗 METTL3 可减轻 KOA 模型大鼠的软骨损伤、炎症反应、铁蛋白沉积和膝关节疼痛,而添加 HMGB1 则可逆转这些影响。总之,通过调节 HMGB1,消耗 METTL3 可抑制铁蛋白沉积和炎症反应,并改善 KOA 进展过程中的软骨损伤和膝关节疼痛。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Cell Biology International
Cell Biology International 生物-细胞生物学
CiteScore
7.60
自引率
0.00%
发文量
208
审稿时长
1 months
期刊介绍: Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect. These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.
×
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