Abstract:
INTRODUCTION:miR-146a is one of the first identified miRNAs expressed differentially in osteoarthritis (OA) cartilage. However, the role it plays in OA pathogenesis is not clear. The aim of this study is to identify a molecular target of miR-146a, thereby elucidating its function in chondrocytes during OA pathogenesis. METHODS:Primary chondrocytes from Sprague-Dawley rats were treated with IL-1β before the expression levels of miR-146a, Smad4 and vascular endothelial growth factor (VEGF) were quantified by real-time PCR and/or western blotting. The effect of miR-146a on cellular response to transforming growth factor (TGF)-β1 was quantified by a luciferase reporter harboring TGF-β1 responsive elements and by extracellular signal-regulated kinase assay. The effect of miR-146a on apoptosis was quantified by the TUNEL assay. OA pathogenesis was surgically induced with joint instability in rats, evaluated by histopathological analysis with safranin O staining, and the expression levels of miR-146a, Smad4, and VEGF were quantified using real-time PCR and/or immunohistochemistry. RESULTS:IL-1β treatment of chondrocytes increased the expression levels of miR-146a and VEGF and decreased the levels of Smad4 in a time-dependent manner. miR-146a upregulated VEGF expression and downregulated Smad4 expression in chondrocytes, while a miR-146a inhibitor acted in a converse manner. Smad4, a common mediator of the TGF-β pathway, is identified as a direct target of miR-146a by harboring a miR-146a binding sequence in the 3'-UTR region of its mRNA. Mutation of the binding sequence significantly relieved the inhibition of the Smad4 reporter activity by miR-146a. Furthermore, miR-146a upregulation of VEGF is mediated by Smad4. Expression of miR-146a led to a reduction of cellular responsiveness to TGF-β and an increase of apoptosis rate in chondrocytes. In vivo, cartilage from surgically induced OA rats displayed higher levels of miR-146a and VEGF compared with the sham group. In contrast, Smad4 expression level was lower in the OA group than the sham group. CONCLUSION:IL-1β responsive miR-146a is overexpressed in an experimentally induced OA model, accompanied by upregulation of VEGF and downregulation of Smad4 in vivo. miR-146a may contribute to OA pathogenesis by increasing VEGF levels and by impairing the TGF-β signaling pathway through targeted inhibition of Smad4 in cartilage.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Li J,Huang J,Dai L,Yu D,Chen Q,Zhang X,Dai Kdoi
10.1186/ar3798subject
Has Abstractpub_date
2012-04-16 00:00:00pages
R75issue
2eissn
1478-6354issn
1478-6362pii
ar3798journal_volume
14pub_type
杂志文章abstract:INTRODUCTION:Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) share genetic and clinical features. IBD is associated with the presence of antibodies to a variety of commensal microorganisms including anti-Saccharomyces cerevesiae antibodies (ASCA), antineutrophil cytoplasmic antibodies (ANCA), anti-I2 (...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4350
更新日期:2013-10-26 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-014-0411-6
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Rheumatoid arthritis (RA) patients are treated with a mean of 3-4 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) with or without glucocorticoids (GCs), before the first biologic prescription. The main reasons for change are inefficacy in 30-40 % of patients, and toxicity ≈ 10 %. Thus...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-016-1137-4
更新日期:2016-11-08 00:00:00
abstract::Autoantibodies to neutrophil cytoplasmic antigen-associated vasculitis (AAV) is characterised by inflammation of blood vessels. The introduction of immunosuppressive therapy with glucocorticoids and cyclophosphamide transformed AAV from a fatal condition to a largely treatable condition. Over the past 30 years, consid...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3797
更新日期:2012-04-30 00:00:00
abstract::Synovial fluid from patients with various arthritides contains procoagulant, cell-derived microparticles. Here we studied whether synovial microparticles modulate the release of chemokines and cytokines by fibroblast-like synoviocytes (FLS). Microparticles, isolated from the synovial fluid of rheumatoid arthritis (RA)...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1706
更新日期:2005-01-01 00:00:00
abstract::Cardiovascular event rates are markedly increased in rheumatoid arthritis (RA), and RA atherogenesis remains poorly understood. The relative contributions of traditional and nontraditional risk factors to cardiovascular disease in RA await elucidation. The present study comprises three components. First, we compared b...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1717
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:The aim was to describe the regulatory B and T cells (Breg and Treg) and T helper 17 (Th17) lymphocytes before and under treatment with biologic drugs, and to assess their potential predictive value as biomarkers of response in rheumatoid arthritis (RA). METHODS:This was a non-randomised, single-centre, pro...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/s13075-017-1244-x
更新日期:2017-02-10 00:00:00
abstract:INTRODUCTION:Rheumatoid arthritis (RA) is considered a T cell driven autoimmune disease, therefore, the ability of B cell depleting biologics, e.g., anti-CD20 antibodies, to alleviate RA is unclear. This study examined the proportions of IL-17-secreting lymphocytes in the blood of healthy subjects and RA patients and d...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3541
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Differential diagnosis among psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (Abneg RA) can be challenging particularly in the clinical setting of peripheral phenotype and autoantibodies seronegativity. The aim of the study was to identify synovial tissue (ST) biomarkers differentially expres...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-1898-7
更新日期:2019-05-09 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 社论
doi:10.1186/s13075-015-0878-9
更新日期:2015-12-07 00:00:00
abstract:INTRODUCTION:The purpose of this study was to examine data from the Johnston County Osteoarthritis (OA) Project for independent associations of educational attainment, occupation and community poverty with tibiofemoral knee OA. METHODS:A cross-sectional analysis was conducted on 3,591 individuals (66% Caucasian and 34...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3492
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Determining the association between body composition and low back pain (LBP) will improve our understanding of the mechanisms by which obesity affects LBP, and inform novel approaches to managing LBP. The aim of this study was to examine the relationship between body composition and LBP intensity and disabi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1242-z
更新日期:2017-02-10 00:00:00
abstract::Following publication of the original article [1], the authors reported a typesetting error. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,已发布勘误
doi:10.1186/s13075-018-1753-2
更新日期:2018-11-05 00:00:00
abstract::We analyzed the clinical response and the time to relapse after discontinuation of continuous long-term infliximab therapy in patients with ankylosing spondylitis (AS). After 3 years of infliximab therapy, all AS patients (n = 42) discontinued treatment (time point (TP)1) and were visited regularly for 1 year in order...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/ar1693
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Here we integrate verified signals from previous genetic association studies with gene expression and pathway analysis for discovery of new candidate genes and signaling networks, relevant for rheumatoid arthritis (RA). METHOD:RNA-sequencing-(RNA-seq)-based expression analysis of 377 genes from previously v...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1220-5
更新日期:2017-02-02 00:00:00
abstract::Pleiotropic effects are now described for the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (or statins) that might have utility in the context of chronic inflammatory autoimmune disease. Here we discuss the pharmacology and established uses of statins and in this context describe potential anti-inflammat...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1496
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Nucleus pulposus (NP) cells have a phenotype similar to articular cartilage (AC) cells. However, the matrix of the NP is clearly different to that of AC suggesting that specific cell phenotypes exist. The aim of this study was to identify novel genes that could be used to distinguish bovine NP cells from A...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2929
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:The pathogenesis of sacroiliitis is unclear; therefore, we aimed to systematically study the immunopathology of sacroiliitis in patients with axial spondyloarthritis (axSpA), and explore the relationship between pannus formation, inflammation, and the structural damage caused by sacroiliitis. METHODS:Fine n...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1594-z
更新日期:2018-06-08 00:00:00
abstract::In rheumatoid arthritis, T cells, B cells, macrophages, and dendritic cells invade the synovial membranes, establishing complex microstructures that promote inflammatory/tissue destructive lesions. B cell involvement has been considered to be limited to autoantibody production. However, recent studies suggest that B c...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1737
更新日期:2005-01-01 00:00:00
abstract::Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages secreting high amounts of inflammatory cytokines. It is a frequent manifestation in patients with predisposing genetic defects, but can o...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3843
更新日期:2012-06-08 00:00:00
abstract:INTRODUCTION:Data from clinical studies on the long-term efficacy and safety of anti-tumor necrosis factor (TNF)-α therapy in patients with ankylosing spondylitis (AS) are scarce. This is the first report on continuous treatment with the TNFα fusion protein etanercept over seven years (y). METHODS:Overall, 26 patients...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/ar4244
更新日期:2013-01-01 00:00:00
abstract::Behçet's disease is characterized by recurrent aphthous stomatitis, uveitis, genital ulcers, and skin lesions. The role of the HLA-B*51 gene has been confirmed in recent years, although its contribution to the overall genetic susceptibility to Behçet's disease was estimated to be only 19%. The production of a variety ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar757
更新日期:2003-01-01 00:00:00
abstract::Macrophage activation syndrome (MAS) has been reported in association with many rheumatic diseases, most commonly in systemic juvenile rheumatoid arthritis (sJRA). Clinically, MAS is similar to hemophagocytic lymphohistiocytosis (HLH), a genetic disorder with absent or depressed natural killer (NK) function. We have p...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1453
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:It is known that anticitrullinated peptide antibody (ACPA)-positive rheumatoid arthritis (RA) has a preclinical phase. Whether this phase is also present in ACPA-negative RA is unknown. To determine this, we studied ACPA-negative arthralgia patients who were considered prone to progress to RA for local sub...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4536
更新日期:2014-04-10 00:00:00
abstract:BACKGROUND:The aim of this study was to understand whether acupuncture can decrease the risk of coronary heart disease (CHD) in patients with fibromyalgia. METHODS:Using data from the Taiwanese National Health Insurance Research Database, we performed a propensity score-matched cohort study to analyze patients with fi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1239-7
更新日期:2017-02-28 00:00:00
abstract:BACKGROUND:Systemic sclerosis (SSc) is characterized by early vascular abnormalities and subsequent fibroblast activation to myofibroblasts, leading to fibrosis. Recently, endothelial-to-mesenchymal transition (EndoMT), a complex biological process in which endothelial cells lose their specific markers and acquire a me...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1122-y
更新日期:2016-10-06 00:00:00
abstract:INTRODUCTION:Physical activity has been recommended to patients with knee osteoarthritis for improving their symptoms. However, it is still controversial if physical activity has effects on joint structures including cartilage volume. The aim of this study was to describe the associations between physical activity and ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0813-0
更新日期:2015-10-26 00:00:00
abstract:BACKGROUND:Increased expression of toll-like receptor 4 (TLR4) and its endogenous ligands, is characteristic of rheumatoid arthritis (RA) synovitis. In this study, we evaluated how these TLR4 ligands may drive pathogenic processes and whether the fine profiling of anti-citrullinated protein antibodies (ACPA) based on t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1128-5
更新日期:2016-10-06 00:00:00
abstract:INTRODUCTION:Prostaglandin D synthase (PGDS) is responsible for the biosynthesis of PGD and J series, which have been shown to exhibit anti-inflammatory and anticatabolic effects. Two isoforms have been identified: hematopoietic- and lipocalin-type PGDS (H-PGDS and L-PGDS, respectively). The aims of this study were to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2581
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:The receptor activator of NF-κB ligand (RANKL), a member of the TNF ligand superfamily, is known to regulate bone metabolism. The expression of each component of the RANK/RANKL/osteoprotegerin (OPG) system in the intervertebral disc (IVD) has not been examined in detail. The purposes of this study were to ex...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1332-y
更新日期:2017-06-02 00:00:00