Metabolic Reprogramming in Stromal and Immune Cells in Rheumatoid Arthritis and Osteoarthritis: Therapeutic Possibilities

IF 4.5 3区 医学 Q2 IMMUNOLOGY
Órlaith C. Henry, Luke A. J. O'Neill
{"title":"Metabolic Reprogramming in Stromal and Immune Cells in Rheumatoid Arthritis and Osteoarthritis: Therapeutic Possibilities","authors":"Órlaith C. Henry,&nbsp;Luke A. J. O'Neill","doi":"10.1002/eji.202451381","DOIUrl":null,"url":null,"abstract":"<p>Metabolic reprogramming of stromal cells, including fibroblast-like synoviocytes (FLS) and chondrocytes, as well as osteoclasts (OCs), are involved in the inflammatory and degenerative processes underlying rheumatoid arthritis (RA) and osteoarthritis (OA). In RA, FLS exhibit mTOR activation, enhanced glycolysis and reduced oxidative phosphorylation, fuelling inflammation, angiogenesis, and cartilage degradation. In OA, chondrocytes undergo metabolic rewiring, characterised by mTOR and NF-κB activation, mitochondrial dysfunction, and increased glycolysis, which promotes matrix metalloproteinase production, extracellular matrix (ECM) degradation, and angiogenesis. Macrophage-derived immunometabolites, including succinate and itaconate further modulate stromal cell function, acting as signalling molecules that modulate inflammatory and catabolic processes. Succinate promotes inflammation whilst itaconate is anti-inflammatory, suppressing inflammatory joint disease in models. Itaconate deficiency also correlates inversely with disease severity in RA in humans. Emerging evidence highlights the potential of targeting metabolic processes as promising therapeutic strategies for connective tissue disorders.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 4","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451381","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/eji.202451381","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Metabolic reprogramming of stromal cells, including fibroblast-like synoviocytes (FLS) and chondrocytes, as well as osteoclasts (OCs), are involved in the inflammatory and degenerative processes underlying rheumatoid arthritis (RA) and osteoarthritis (OA). In RA, FLS exhibit mTOR activation, enhanced glycolysis and reduced oxidative phosphorylation, fuelling inflammation, angiogenesis, and cartilage degradation. In OA, chondrocytes undergo metabolic rewiring, characterised by mTOR and NF-κB activation, mitochondrial dysfunction, and increased glycolysis, which promotes matrix metalloproteinase production, extracellular matrix (ECM) degradation, and angiogenesis. Macrophage-derived immunometabolites, including succinate and itaconate further modulate stromal cell function, acting as signalling molecules that modulate inflammatory and catabolic processes. Succinate promotes inflammation whilst itaconate is anti-inflammatory, suppressing inflammatory joint disease in models. Itaconate deficiency also correlates inversely with disease severity in RA in humans. Emerging evidence highlights the potential of targeting metabolic processes as promising therapeutic strategies for connective tissue disorders.

Abstract Image

求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
×
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