Abstract:
OBJECTIVES:Systemic sclerosis (SSc) fibroblasts remain activated even in the absence of exogenous stimuli. Epigenetic alterations are thought to play a role for this endogenous activation. Trimethylation of histone H3 on lysine 27 (H3K27me3) is regulated by Jumonji domain-containing protein 3 (JMJD3) and ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) in a therapeutically targetable manner. The aim of this study was to explore H3K27me3 demethylases as potential targets for the treatment of fibrosis. METHODS:JMJD3 was inactivated by small interfering RNA-mediated knockdown and by pharmacological inhibition with GSKJ4. The effects of targeted inactivation of JMJD3 were analysed in cultured fibroblasts and in the murine models of bleomycin-induced and topoisomerase-I (topoI)-induced fibrosis. H3K27me3 at the FRA2 promoter was analysed by ChIP. RESULTS:The expression of JMJD3, but not of UTX, was increased in fibroblasts in SSc skin and in experimental fibrosis in a transforming growth factor beta (TGFβ)-dependent manner. Inactivation of JMJD3 reversed the activated fibroblast phenotype in SSc fibroblasts and prevented the activation of healthy dermal fibroblasts by TGFβ. Pharmacological inhibition of JMJD3 ameliorated bleomycin-induced and topoI-induced fibrosis in well-tolerated doses. JMJD3 regulated fibroblast activation in a FRA2-dependent manner: Inactivation of JMJD3 reduced the expression of FRA2 by inducing accumulation of H3K27me3 at the FRA2 promoter. Moreover, the antifibrotic effects of JMJD3 inhibition were reduced on knockdown of FRA2. CONCLUSION:We present first evidence for a deregulation of JMJD3 in SSc. JMJD3 modulates fibroblast activation by regulating the levels of H3K27me3 at the promoter of FRA2. Targeted inhibition of JMJD3 limits the aberrant activation of SSc fibroblasts and exerts antifibrotic effects in two murine models.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Bergmann C,Brandt A,Merlevede B,Hallenberger L,Dees C,Wohlfahrt T,Pötter S,Zhang Y,Chen CW,Mallano T,Liang R,Kagwiria R,Kreuter A,Pantelaki I,Bozec A,Abraham D,Rieker R,Ramming A,Distler O,Schett G,Distler JHWdoi
10.1136/annrheumdis-2017-211501subject
Has Abstractpub_date
2018-01-01 00:00:00pages
150-158issue
1eissn
0003-4967issn
1468-2060pii
annrheumdis-2017-211501journal_volume
77pub_type
杂志文章abstract::Ten patients (8 female, 2 male) with systemic lupus erythematosus (SLE) were entered into an open trial with the anabolic steroid 19-nortestosterone (19-nor). Their clinical condition did not improve, nor were significant changes observed in the majority of laboratory data. However, overall the platelet count rose, an...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章
doi:10.1136/ard.42.2.155
更新日期:1983-04-01 00:00:00
abstract::One hundred acute geriatric inpatients were assessed to investigate the prevalence of shoulder disorders; 21 had symptoms due to shoulder disease. Conditions included supraspinatus tendinitis (five), chronic rotator cuff rupture (seven), frozen shoulder (two), glenohumeral osteoarthritis (two), apatite related shoulde...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.46.9.684
更新日期:1987-09-01 00:00:00
abstract::Antibody production in response to the primary immunogen bacteriophage phi X174 was investigated in 14 patients with previous yersinia arthritis (YA) and in 15 controls. HLA-B27 occurred in 10 patients with YA and in three controls. After primary and secondary immunisation the antibody responses were essentially simil...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.46.12.883
更新日期:1987-12-01 00:00:00
abstract:OBJECTIVE:To describe the associations between overweight measures in childhood and knee pain, stiffness and dysfunction among adults 25 years later. METHODS:Subjects broadly representative of the Australian population (n=449, aged 31-41 years, female 48%) were selected from the Australian Schools Health and Fitness S...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204161
更新日期:2015-04-01 00:00:00
abstract::To establish the prevalence of inflammatory bowel disease in ankylosing spondylitis (AS), 79 AS patients underwent detailed medical screening, including sigmoidoscopic and roentgenological examination, 48 had gastrointestinal symptoms and the others did not. In 3 patients a diagnosis of Crohn's disease was made which ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.37.1.30
更新日期:1978-02-01 00:00:00
abstract:OBJECTIVES:Factors contributing to the development of systemic lupus erythematosus (SLE) remain largely unknown although are likely to include both environmental and genetic components. Studies on murine lupus have indicated a role for an antibody that blocks binding of cytotoxic T lymphocyte associated-4 (CTLA-4) to B...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.58.3.193
更新日期:1999-03-01 00:00:00
abstract::Patients who develop reactive arthritis after yersinia enteritis are characterised by high and persisting IgA-anti-yersinia antibodies. We have further analysed the humoral immune response to yersinia in this condition. Total concentrations of IgM, IgG, IgA, and secretory IgA in the serum and specific anti-yersinia an...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.45.7.561
更新日期:1986-07-01 00:00:00
abstract::Using an in vitro system of cell migration from glass capillary tubes, the nonsteroidal, anti-inflammatory agents sodium salicylate, aspirin, ibuprofen, phenylbutazone, and indomethacin were shown to inhibit the migration of human peripheral leucocytes in a dose-related manner. This drug action was not confined to one...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.36.3.239
更新日期:1977-06-01 00:00:00
abstract::A 49 year old man is described with a polyarticular arthritis. Synovial fluid aspirated from the knee joint showed monosodium urate monohydrate and calcium pyrophosphate dihydrate by polarised light microscopy. Additionally, diphosphonate binding and scanning electron microscopy with energy dispersive analysis showed ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.47.10.864
更新日期:1988-10-01 00:00:00
abstract::Cultures of synovial cells obtained at surgery from patients with rheumatoid arthritis produced a protein which inhibits the mitosis of normal rabbit and human synovial cells, and of human lung fibroblasts. This mitotic inhibitory effect can be transferred to rabbit synovial cells by intra-articular injection of the a...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.37.2.187
更新日期:1978-04-01 00:00:00
abstract:OBJECTIVE:To analyse fibronectin (FN) gene polymorphisms in type II mixed cryoglobulinemic syndrome (MCsn), an immune-complex mediated systemic vasculitis linked to hepatitis C virus (HCV) infection and characterised by rheumatoid factor (RF) positive B-cell proliferation at high risk for the progression into non-Hodgk...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2006.067637
更新日期:2008-01-01 00:00:00
abstract::A study of 163 patients with ankylosing spondylitis seen on 433 occasions showed that active inflammatory disease was strongly associated with the presence of Klebsiella pneumoniae in the faeces (P less than 0.001). Sequential studies showed that in patients with inactive disease the presence of a positive culture for...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.37.2.146
更新日期:1978-04-01 00:00:00
abstract:OBJECTIVE:To assess how socioeconomic deprivation influences the presentation, treatment, and outcome of patients with rheumatoid arthritis (RA). METHODS:Three year follow up of 869 consecutive patients with RA from nine hospital rheumatology clinics, with patients categorised by the Carstairs deprivation score of the...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.59.10.794
更新日期:2000-10-01 00:00:00
abstract::A patient with systemic lupus erythematosus was first diagnosed after she had developed the Budd-Chiari syndrome. We believe that the Budd-Chiari syndrome was part of her tendency for thrombosis, induced by the presence of a lupus anticoagulant. The association between enhanced thrombosis and the lupus anticoagulant i...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.45.5.435
更新日期:1986-05-01 00:00:00
abstract::We showed previously that the attachment of synovial fibroblasts to laminin (LM)-111 in the presence of transforming growth factor-beta induces significant expression of the matrix metalloproteinase (MMP)-3. Here we go on to investigate the regulation of additional MMPs and their specific tissue inhibitors of matrix p...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.073809
更新日期:2008-04-01 00:00:00
abstract:OBJECTIVE:Sacroiliitis is a hallmark of the spondyloarthropathies (SpA). The degree of inflammation can be quantified by magnetic resonance imaging (MRI). The aim of this study was to further elucidate the pathogenesis of SpA by quantitative cellular analysis of immunostained sacroiliac biopsy specimens and to compare ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.59.2.135
更新日期:2000-02-01 00:00:00
abstract:BACKGROUND:In 2001, the European League Against Rheumatism developed and disseminated the first guidelines for musculoskeletal (MS) ultrasound (US) in rheumatology. Fifteen years later, the dramatic expansion of new data on MSUS in the literature coupled with technological developments in US imaging has necessitated an...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,实务指引
doi:10.1136/annrheumdis-2017-211585
更新日期:2017-12-01 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:BACKGROUND:Collagen-induced arthritis (CIA) is the most commonly used model of rheumatoid arthritis (RA). In both CIA and RA there is an increase in the cellular content of the synovium, this being dominated by macrophages. OBJECTIVE:To assess the impact of etoposide, a topoisomerase II antagonist known to induce mono...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.61.9.829
更新日期:2002-09-01 00:00:00
abstract::Thermography before and after joint irrigation at arthroscopy showed no significant improvement of inflammation in 14 patients. Subjectively, those with chondrocalcinosis did best. ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.37.1.78
更新日期:1978-02-01 00:00:00
abstract:OBJECTIVES:To investigate the hypothesis that synovial fluid (SF) from patients with osteoarthritis (OA) may contain calcium phosphate crystals that are either too small, or too few in number to be identified by conventional light microscopy techniques. METHODS:Twelve SF from 11 patients with established knee OA, five...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.53.7.467
更新日期:1994-07-01 00:00:00
abstract:OBJECTIVES:To report 4-year imaging outcomes in the RAPID-axSpA (NCT01087762) study of patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA), treated with certolizumab pegol (CZP). METHODS:This phase III, randomised trial was placebo-controlled and double-blind to week 24, d...
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/annrheumdis-2017-212377
更新日期:2018-05-01 00:00:00
abstract:BACKGROUND:We report on a workshop on ethical and legal constraints on data sharing between countries in multinational epidemiologic research in Europe that was held in January 2007 in Potsdam, Germany. The participants were experienced epidemiologic and clinical researchers from eight European countries. The aim of th...
journal_title:Annals of the rheumatic diseases
pub_type: 共识发展会议,杂志文章
doi:10.1136/ard.2007.080598
更新日期:2008-07-01 00:00:00
abstract::A 35 year old woman presented with headache and fever. Computed brain tomography showed diffuse low attenuation in the cerebral white matter. Several months later, serological tests for systemic lupus erythematosus (SLE) became positive. In spite of immunosuppressive therapy she relapsed after six months of treatment,...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.46.2.162
更新日期:1987-02-01 00:00:00
abstract::Ultrasound (US) unquestionably improves many aspects of rheumatoid arthritis (RA) diagnosis and management, but no consensus has been reached regarding the optimal US methodology that should be used, and high levels of standardisation have not yet been attained. Current evidence from two randomised controlled trials d...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/annrheumdis-2017-211458
更新日期:2018-01-01 00:00:00
abstract:OBJECTIVES:In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly known. Therefore, we aimed to determine sex effects on outcomes. METHOD:We performed a prospective observational...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2014-206386
更新日期:2016-01-01 00:00:00
abstract:OBJECTIVE:To study the ability of low-cost low-field dedicated extremity magnetic resonance imaging (E-MRI) to assess and predict erosive joint damage in the wrist and metacarpophalangeal (MCP) joints of patients with early rheumatoid arthritis. METHODS:24 previously untreated patients with rheumatoid arthritis with j...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2005.049213
更新日期:2006-09-01 00:00:00
abstract::A 60-year-old man with destructive rheumatoid disease, multiple nodules, and vasculitis developed a facial rash with ulceration and scarring. Histology showed granulomatous vasculitis. The rash was rapidly controlled with oral corticosteroids. Granulomatous vasculitis has not previously been reported as causing this c...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.45.1.75
更新日期:1986-01-01 00:00:00
abstract::The aim of this report was to propose a definition for erosive disease in the context of inflammatory arthritis in light of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) criteria for use in clinical practice and studies. A EULAR task force was form...
journal_title:Annals of the rheumatic diseases
pub_type: 共识发展会议,杂志文章
doi:10.1136/annrheumdis-2012-202779
更新日期:2013-04-01 00:00:00
abstract:OBJECTIVE:To evaluate the presence of anti-PDGFR-alpha antibodies by immunological methods in patients with systemic sclerosis (SSc). METHODS:Fifty-eight women diagnosed with SSc and 36 healthy women controls were included. IgG anti-PDGFR-alpha were measured by ELISA and immunoblot. Associations with clinical and immu...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.085480
更新日期:2008-07-01 00:00:00