{"title":"Metabolic Reprogramming in Stromal and Immune Cells in Rheumatoid Arthritis and Osteoarthritis: Therapeutic Possibilities","authors":"Órlaith C. Henry, 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.
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.