scholarly journals Critical Role of Glucose Metabolism in Rheumatoid Arthritis Fibroblast-like Synoviocytes

2016 ◽  
Vol 68 (7) ◽  
pp. 1614-1626 ◽  
Author(s):  
Ricard Garcia-Carbonell ◽  
Ajit S. Divakaruni ◽  
Alessia Lodi ◽  
Ildefonso Vicente-Suarez ◽  
Arindam Saha ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Glucose Metabolism ◽  
Critical Role ◽  
Fibroblast Like Synoviocytes

Role of glucose metabolism in aggressive phenotype of fibroblast-like synoviocytes: Latest evidence and therapeutic approaches in rheumatoid arthritis

2020 ◽  
Vol 89 ◽  
pp. 107064
Author(s):  
Maryam Masoumi ◽  
Mohsen Mehrabzadeh ◽  
Salman Mahmoudzehi ◽  
Mohammad Javad Mousavi ◽  
Sirous Jamalzehi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Glucose Metabolism ◽  
Therapeutic Approaches ◽  
Aggressive Phenotype ◽  
Fibroblast Like Synoviocytes

scholarly journals A critical role of Cyr61 in interleukin-17–dependent proliferation of fibroblast-like synoviocytes in rheumatoid arthritis

2009 ◽  
Vol 60 (12) ◽  
pp. 3602-3612 ◽  
Author(s):  
Qiuyu Zhang ◽  
Juanjuan Wu ◽  
Qi Cao ◽  
Lianbo Xiao ◽  
Li Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Critical Role ◽  
Interleukin 17A ◽  
Fibroblast Like Synoviocytes

scholarly journals Hexokinase 2 as a novel selective metabolic target for rheumatoid arthritis

2018 ◽  
Vol 77 (11) ◽  
pp. 1636-1643 ◽  
Author(s):  
Marta F Bustamante ◽  
Patricia G Oliveira ◽  
Ricard Garcia-Carbonell ◽  
Adam P Croft ◽  
Jeff M Smith ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Glucose Metabolism ◽  
Cartilage Damage ◽  
Critical Role ◽  
Lactate Production ◽  
Migration And Invasion ◽  
Synovial Lining ◽  
Serum Transfer ◽  
And Cartilage

ObjectivesRecent studies indicate that glucose metabolism is altered in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Hexokinases (HKs) catalyse the first step in glucose metabolism, and HK2 constitutes the principal HK inducible isoform. We hypothesise that HK2 contributes to the synovial lining hypertrophy and plays a critical role in bone and cartilage damage.MethodsHK1 and HK2 expression were determined in RA and osteoarthritis (OA) synovial tissue by immunohistochemistry. RA FLS were transfected with either HK1 or HK2 siRNA, or infected with either adenovirus (ad)-GFP, ad-HK1 or ad-HK2. FLS migration and invasion were assessed. To study the role of HK2 in vivo, 108 particles of ad-HK2 or ad-GFP were injected into the knee of wild-type mice. K/BxN serum transfer arthritis was induced in HK2F/F mice harbouring Col1a1-Cre (HK2Col1), to delete HK2 in non-haematopoietic cells.ResultsHK2 is particular of RA histopathology (9/9 RA; 1/8 OA) and colocalises with FLS markers. Silencing HK2 in RA FLS resulted in a less invasive and migratory phenotype. Consistently, overexpression of HK2 resulted in an increased ability to migrate and invade. It also increased extracellular lactate production. Intra-articular injection of ad-HK2 in normal knees dramatically increased synovial lining thickness, FLS activation and proliferation. HK2 was highly expressed in the synovial lining after K/BxN serum transfer arthritis. HK2Col1 mice significantly showed decreased arthritis severity, bone and cartilage damage.ConclusionHK2 is specifically expressed in RA synovial lining and regulates FLS aggressive functions. HK2 might be an attractive selective metabolic target safer than global glycolysis for RA treatment.

Development of an ex vivo cellular model of rheumatoid arthritis: Critical role of cd14-positive monocyte/macrophages in the development of pannus tissue

2007 ◽  
Vol 56 (9) ◽  
pp. 2875-2885 ◽  
Author(s):  
Toshiko Nozaki ◽  
Kyoko Takahashi ◽  
Osamu Ishii ◽  
Sachio Endo ◽  
Kyoji Hioki ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ex Vivo ◽  
Critical Role ◽  
Cellular Model ◽  
Pannus Tissue

scholarly journals The Pivotal Role of TBK1 in Inflammatory Responses Mediated by Macrophages

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Tao Yu ◽  
Young-Su Yi ◽  
Yanyan Yang ◽  
Jueun Oh ◽  
Deok Jeong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Cell Damage ◽  
Critical Role ◽  
Biological Response ◽  
Antiviral Defense ◽  
Functional Roles ◽  
Virus Interaction

Inflammation is a complex biological response of tissues to harmful stimuli such as pathogens, cell damage, or irritants. Inflammation is considered to be a major cause of most chronic diseases, especially in more than 100 types of inflammatory diseases which include Alzheimer's disease, rheumatoid arthritis, asthma, atherosclerosis, Crohn's disease, colitis, dermatitis, hepatitis, and Parkinson's disease. Recently, an increasing number of studies have focused on inflammatory diseases. TBK1 is a serine/threonine-protein kinase which regulates antiviral defense, host-virus interaction, and immunity. It is ubiquitously expressed in mouse stomach, colon, thymus, and liver. Interestingly, high levels of active TBK1 have also been found to be associated with inflammatory diseases, indicating that TBK1 is closely related to inflammatory responses. Even though relatively few studies have addressed the functional roles of TBK1 relating to inflammation, this paper discusses some recent findings that support the critical role of TBK1 in inflammatory diseases and underlie the necessity of trials to develop useful remedies or therapeutics that target TBK1 for the treatment of inflammatory diseases.

CXCL10 and TRAIL Are Upregulated by TXNDC5 in Rheumatoid Arthritis Fibroblast-like Synoviocytes

2017 ◽  
Vol 45 (3) ◽  
pp. 335-340 ◽  
Author(s):  
Bing Xu ◽  
Jian Li ◽  
Changsun Wu ◽  
Chunyan Liu ◽  
Xinfeng Yan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Synovial Fibroblasts ◽  
And Migration ◽  
Interfering Rna ◽  
Synovial Membranes ◽  
Necrosis Factor ◽  
Fibroblast Like Synoviocytes

Objective.Thioredoxin domain containing 5 (TXNDC5) is highly expressed in synovial membranes of rheumatoid arthritis (RA). Our study aimed to investigate the pathogenic role of TXNDC5 in RA.Methods.PCR arrays, CCK-8 assays, flow cytometry, and transwell migration assays were used to analyze cultured rheumatoid arthritis synovial fibroblasts (RASF).Results.Increased CXCL10 and tumor necrosis factor-related apoptosis-inducing ligand levels were detected in RASF transfected with anti-TXNDC5 small interfering RNA (siRNA), and decreased expression was detected in RASF transfected with TXNDC5-expressing plasmids. Significantly attenuated RASF proliferation and migration, and increased RASF apoptosis, were observed in the siRNA-transfected RASF.Conclusion.Downregulation of TXNDC5 could contribute to RASF antiangiogenic and proapoptotic features through the suppression of CXCL10 and TRAIL (tumor necrosis factor-related apoptosis-inducing ligand).

scholarly journals Dysregulation of lncRNAs in Rheumatoid Arthritis: Biomarkers, Pathogenesis and Potential Therapeutic Targets

2021 ◽  
Vol 12 ◽  
Author(s):  
Chenggui Miao ◽  
Liangliang Bai ◽  
Yaru Yang ◽  
Jinling Huang
Keyword(s):  
Rheumatoid Arthritis ◽  
Epigenetic Modification ◽  
Joint Destruction ◽  
Research Progress ◽  
Unknown Etiology ◽  
Signal Pathways ◽  
Cartilage Erosion ◽  
Chronic Autoimmune Disease ◽  
Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology, mainly manifested by persistent abnormal proliferation of fibroblast-like synoviocytes (FLSs), inflammation, synovial hyperplasia and cartilage erosion, accompanied by joint swelling and joint destruction. Abnormal expression or function of long noncoding RNAs (lncRNAs) are closely related to human diseases, including cancers, mental diseases, autoimmune diseases and others. The abnormal sequence and spatial structure of lncRNAs, the disorder expression and the abnormal interaction with the binding protein will lead to the change of gene expression in the way of epigenetic modification. Increasing evidence demonstrated that lncRNAs were involved in the activation of FLSs, which played a key role in the pathogenesis of RA. In this review, the research progress of lncRNAs in the pathogenesis of RA was systematically summarized, including the role of lncRNAs in the diagnosis of RA, the regulatory mechanism of lncRNAs in the pathogenesis of RA, and the intervention role of lncRNAs in the treatment of RA. Furthermore, the activated signal pathways, the role of DNA methylation and other mechanism have also been overview in this review.

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