Abstract:
OBJECTIVE:Notch signalling pathways are critical for angiogenesis and endothelial cell (EC) fate; however the mechanisms regulating these processes in the inflamed joint remain to be elucidated. Here, we examine whether Notch signalling mediates vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2)-induced vascular function. METHODS:Notch-1 intracellular domain (Notch-1 IC), Notch-4 IC, Delta-like-ligand 4, Hes-related transcriptional repressors-1 and 2 (Hrt-1, Hrt-2) mRNA and/or protein expression was measured by Real-time PCR and/or western blot. VEGF/Ang2 induced EC function was assessed using transwell invasion chambers, matrigel tube formation assays and wound repair scratch assays±Notch-1 siRNA or an γ-secretase inhibitor N-(N-(3,5-Difluorophenacetyl-L-alanly))-S-phenylglycine-t-Butyl Ester (DAPT) in RA synovial explants or human microvascular EC. Interleukin (IL)-6 and IL-8 were measured by ELISA and MMP2 and 9 by gelatine zymography. RESULTS:Notch-1 IC and Notch-4 IC protein expressions were demonstrated in RA and psoriatic arthritis synovial biopsies, with minimal expression observed in Osteoarthritis (OA). VEGF and Ang2 induced Notch-1 IC/ Notch-4 IC protein expression in synovial explant cultures and human microvascular EC levels were further potentiated by VEGF/Ang2 stimulation in combination. Notch-1, Delta-like-ligand 4, and Hrt-2 mRNA expression were significantly induced by VEGF and Ang2 alone and in combination. Furthermore VEGF/Ang2-induced EC invasion, angiogenesis and migration were inhibited by Notch-1 siRNA or DAPT. Conditioned media from VEGF/Ang2 stimulated RA synovial explants induced EC tube formation, an effect that was inhibited by DAPT. Finally, DAPT significantly decreased VEGF/Ang2 induced IL-6, IL-8, MMP2 and 9 expressions in RA synovial explants. CONCLUSIONS:Notch-1 mediates VEGF/Ang2-induced angiogenesis and EC invasion in inflammatory arthritis.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Gao W,Sweeney C,Walsh C,Rooney P,McCormick J,Veale DJ,Fearon Udoi
10.1136/annrheumdis-2012-201978subject
Has Abstractpub_date
2013-06-01 00:00:00pages
1080-8issue
6eissn
0003-4967issn
1468-2060pii
annrheumdis-2012-201978journal_volume
72pub_type
杂志文章abstract:OBJECTIVE:Rheumatoid arthritis (RA) accompanies infiltration and activation of monocytes in inflamed joints. We investigated dominant alterations of RA monocytes in bone marrow (BM), blood and inflamed joints. METHODS:CD14+ cells from BM and peripheral blood (PB) of patients with RA and osteoarthritis (OA) were profil...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2017-211649
更新日期:2018-02-01 00:00:00
abstract:OBJECTIVE:To assess associations between joint-specific hand symptoms and self-reported and performance-based functional status. METHODS:Participants were from the population-based Johnston County Osteoarthritis Project. Symptoms in the distal interphalangeal (DIP), proximal interphalangeal (PIP), first carpometacarpa...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2006.057422
更新日期:2007-12-01 00:00:00
abstract:BACKGROUND:A recent study from our laboratory showed that induction of the multidrug resistance related drug efflux pump ABCG2 contributed to acquired resistance of human T cells to the disease modifying antirheumatic drug (DMARD) sulfasalazine (SSZ). OBJECTIVES:To investigate the duration of SSZ resistance and ABCG2 ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2003.006494
更新日期:2004-02-01 00:00:00
abstract::A 62 year old woman taking L-tryptophan developed eosinophilic fasciitis shortly after starting an exercise class. She received prednisone without benefit but improved after azathioprine treatment was started and L-tryptophan was discontinued. As products containing L-tryptophan have recently been implicated in develo...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.50.1.55
更新日期:1991-01-01 00:00:00
abstract:OBJECTIVE:To determine the relationship of disease activity to infections in patients with rheumatoid arthritis (RA). METHODS:From the CORRONA database, the incidence of physician-reported infections in RA patients on stable disease-modifying antirheumatic drug, biological, and corticosteroid therapy for at least 6 mo...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2010.128637
更新日期:2011-05-01 00:00:00
abstract:BACKGROUND:Optimal treatment for rheumatoid arthritis (RA) after inadequate response (IR) to tumour necrosis factor α inhibitors (TNFi) remains uncertain. OBJECTIVE:To compare the efficacy and safety of biological agents after TNFi-IR. METHODS:A systematic literature search was carried out using Medline and Cochrane ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,meta分析,评审
doi:10.1136/annrheumdis-2011-200490
更新日期:2012-08-01 00:00:00
abstract:OBJECTIVE:To determine whether abnormalities in the function of the autonomic nervous system are associated with oral and ocular dryness in rheumatoid arthritis. METHODS:Pupillography was done using an infrared light reflection method (IRIS) to measure both parasympathetic function (constriction latency and the latenc...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.55.9.612
更新日期:1996-09-01 00:00:00
abstract::Joint damage in rheumatoid arthritis is assessed radiologically. Previous studies have not examined in detail its long term progression. We evaluated the overall changes of peripheral joint damage radiologically in 50 rheumatoid patients followed up at one rheumatology centre for 10 years. All peripheral joints were s...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.45.5.373
更新日期:1986-05-01 00:00:00
abstract:BACKGROUND:Knee osteoarthritis (OA) is a major cause of pain and functional limitation in older adults, yet longer-term studies of medical treatment of OA are limited. OBJECTIVE:To evaluate the efficacy and safety of glucosamine and chondroitin sulphate (CS), alone or in combination, as well as celecoxib and placebo o...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1136/ard.2009.120469
更新日期:2010-08-01 00:00:00
abstract:OBJECTIVE:To elucidate the clinical importance of the anti-signal recognition particle (SRP) autoantibody in patients with myositis. METHODS:Retrospective systematic assessment of the clinical, laboratory and histological characteristics of 23 anti-SRP-positive patients from six European centres. Data were compared wi...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2006.052191
更新日期:2006-12-01 00:00:00
abstract::The serological diagnosis of juvenile rheumatoid arthritis (JRA) is difficult, with only 7-10% of patients 19S IgM rheumatoid factor positive. About 60-70% of patients are positive for hidden 19S IgM rheumatoid factor, but this test requires serum separation and is not available in most laboratories. Antiperinuclear f...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.51.3.350
更新日期:1992-03-01 00:00:00
abstract:BACKGROUND:Certain sequences present in the hypervariable region of human leucocyte antigen (HLA)-DRB1 known as the shared epitope (SE) are hypothesised to increase the risk of rheumatoid arthritis (RA), whereas alleles encoding aspartic acid at position 70 (D70 alleles) may have a protective effect. METHODS:Patient H...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2006.067603
更新日期:2007-11-01 00:00:00
abstract:OBJECTIVES:Eosinophils possess pro-inflammatory functions in asthma. However, our recent studies have suggested that innate lymphoid cells type 2 (ILC2s) and eosinophils have proresolving properties in rheumatoid arthritis (RA). Nothing is known yet about the mechanisms determining the double-edged role of eosinophils....
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2020-218902
更新日期:2020-11-04 00:00:00
abstract:BACKGROUND:A number of tumour necrosis factor α (TNFα) antagonists (anti-TNFα) are available to treat rheumatoid arthritis. All of these have demonstrated considerable efficacy in placebo controlled trials, but few head-to-head comparisons exist to date. This work's objective is to estimate the relative efficacy among ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,meta分析
doi:10.1136/annrheumdis-2011-200228
更新日期:2012-02-01 00:00:00
abstract::This paper looks at the problem confronting a doctor evaluating a patient with anticentromere antibody who does not have evidence of disease along the spectrum from CREST (calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia) to progressive systemic sclerosis. Of 33 people with anti...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.48.9.771
更新日期:1989-09-01 00:00:00
abstract:OBJECTIVES:To present and analyse the literature sources regarding the management of Behçet disease (BD) identified during the systematic literature research, which formed the basis for the European League Against Rheumatism (EULAR) evidence-based recommendations for the management of BD. METHODS:Problem areas and rel...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.2008.087957
更新日期:2009-10-01 00:00:00
abstract:OBJECTIVES:The severity of joint destruction is highly variable between rheumatoid arthritis (RA) patients. The majority of its heritability is still unexplained. Several autoimmune diseases share genetic risk variants that may also influence disease progression. We aimed to identify genetic risk factors for the severi...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-203375
更新日期:2014-06-01 00:00:00
abstract:OBJECTIVE:To systematically evaluate the association between MRI findings (cartilage defects, bone marrow lesions (BML), osteophytes, meniscal lesion, effusion/synovitis, ligamentous abnormalities, subchondral cysts and bone attrition) and pain in patients with knee osteoarthritis (OA) in order to establish the relevan...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.2010.131904
更新日期:2011-01-01 00:00:00
abstract:OBJECTIVE:To evaluate the presence of flow by Doppler ultrasound (DUS) in the wrist and finger joints (carpometacarpal 1 (CMC1), metacarpophalangeal (MCP), and proximal interphalangeal (PIP) joints) of healthy controls. METHODS:Twenty seven healthy volunteers (15 women, 12 men; mean age 45 years, range 18-93) with a t...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2003.009548
更新日期:2004-06-01 00:00:00
abstract:OBJECTIVES:To determine the diagnostic value of beta 2 microglobulin in parotid saliva, its concentration in relation to salivary flow was determined in 29 patients with primary Sjögren's syndrome and in 30 normal controls. The specific secretion rate of beta 2 microglobulin was calculated. METHODS:Parotid saliva samp...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.52.6.461
更新日期:1993-06-01 00:00:00
abstract::Erosions on the triquetrum and pisiform are frequent in early rheumatoid arthritis and occur characteristically at 3 sites. (a) A shallow erosion on the proximal medial triquetral "bare" area is related to synovial proliferation at the margin of the radiocarpal cavity, although compressive forces from an adjacent long...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.35.1.46
更新日期:1976-02-01 00:00:00
abstract:BACKGROUND:In the synovial membrane of patients with rheumatoid arthritis (RA), a strong expression of laminins and matrix degrading proteases was reported. AIM:To investigate the regulation of matrix metalloproteinases (MMPs) in synovial fibroblasts (SFs) of patients with osteoarthritis (OA) and RA by attachment to l...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2006.060228
更新日期:2007-04-01 00:00:00
abstract::Two patients with sickle cell disease presented with joint pain and early x-ray evidence of articular cartilage loss. Both later developed increasingly destructive arthritis with chronic synovitis identified in synovial biopsies. One patient developed demonstrable aseptic necrosis. Destructive arthropathy is much less...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.36.5.413
更新日期:1977-10-01 00:00:00
abstract::The incidence of exacerbations in the disease course was investigated in 110 patients with systemic lupus erythematosus (SLE) who were studied prospectively at our institute for lupus research. At the time of disease onset and diagnosis the male patients were much older than the female patients (about 10 years); exace...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.48.6.455
更新日期:1989-06-01 00:00:00
abstract::A 46 year old man presented with a growing mass over his wrist. Erosions of the triquetrum and hamate were present radiographically. Magnetic resonance imaging (MRI) showed a solid mass arising from the extensor carpi ulnaris tendon, which was T(1) hypointense and isointense, T(2) hypointense, and bloomed on gradient ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.60.6.550
更新日期:2001-06-01 00:00:00
abstract:OBJECTIVE:The first genome-wide association study (GWAS) of systemic sclerosis (SSc) demonstrated three non-major histocompatibility complex (MHC) susceptibility loci. The goal of this study was to investigate the impact of these gene variants on survival and severity of interstitial lung disease (ILD) in SSc. METHODS...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/annrheumdis-2011-200901
更新日期:2012-07-01 00:00:00
abstract:OBJECTIVE:Ankylosing spondylitis (AS) and periodontal disease (PD) are characterised by dysregulation of the host inflammatory response, resulting in soft and hard connective tissue destruction. AS has been related to other inflammatory diseases, however, there is a paucity of data on whether AS is associated with infl...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2008.097212
更新日期:2010-01-01 00:00:00
abstract:OBJECTIVE:To investigate polymorphisms of both codon 54 allele and promoter variants of the mannose binding lectin (MBL) gene in patients with primary Sjögren's syndrome (SS). METHODS:Polymorphisms of codon 54 allele and promoter variants of the MBL gene in 104 patients with SS and 143 healthy controls were determined...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.60.5.483
更新日期:2001-05-01 00:00:00
abstract::In a search for aspects of behaviour related to oral contraceptive use which might explain the favourable effect of oral contraception on the onset of rheumatoid arthritis (RA), cigarette smoking and alcohol consumption were studied as possible risk factors. Information on cigarette smoking and alcohol consumption was...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.49.12.980
更新日期:1990-12-01 00:00:00
abstract:OBJECTIVES:To develop evidence-based EULAR recommendations for cardiovascular (CV) risk management in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS:A multidisciplinary expert committee was convened as a task force of the EULAR Standing Committee for Clinica...
journal_title:Annals of the rheumatic diseases
pub_type: 共识发展会议,杂志文章,实务指引
doi:10.1136/ard.2009.113696
更新日期:2010-02-01 00:00:00