Abstract:
OBJECTIVE:The zinc-ZIP8-MTF1 axis induces metallothionein (MT) expression and is a catabolic regulator of experimental osteoarthritis (OA) in mice. The main aim of the current study was to explore the roles and underlying molecular mechanisms of MTs in OA pathogenesis. METHODS:Experimental OA in mice was induced by destabilisation of the medial meniscus or intra-articular injection of adenovirus carrying a target gene (Ad-Zip8, Ad-Mtf1, Ad-Epas1, Ad-Nampt, Ad-Mt1 or Ad-Mt2) into wild type, Zip8fl/fl; Col2a1-Cre, Mtf1fl/fl; Col2a1-Cre and Mt1/Mt2 double knockout mice. Primary cultured mouse chondrocytes were infected with Ad-Mt1 or Ad-Mt2, and gene expression profiles analysed via microarray and reverse transcription-PCR. Proteins in human and mouse OA cartilage were identified via immunostaining. Chondrocyte apoptosis in OA cartilage was determined using terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL). RESULTS:MTs were highly expressed in human and mouse OA cartilage. Hypoxia-inducible factor 2α, nicotinamide phosphoribosyltransferase and several proinflammatory cytokine pathways, as well as the zinc-ZIP8-MTF1 axis were identified as upstream regulators of MT expression. Genetic deletion of Mt1 and Mt2 enhanced cartilage destruction through increasing chondrocyte apoptosis. Unexpectedly, aberrant overexpression of MT2, but not MT1, induced upregulation of matrix-degrading enzymes and downregulation of matrix molecules through nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) activation, ultimately leading to OA. CONCLUSIONS:MTs play an antiapoptotic role in post-traumatic OA. However, aberrant and chronic upregulation of MT2 triggers an imbalance between chondrocyte anabolism and catabolism, consequently accelerating OA development. Our findings collectively highlight pleiotropic roles of MTs as regulators of chondrocyte apoptosis as well as catabolic and anabolic pathways during OA pathogenesis.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Won Y,Shin Y,Chun CH,Cho Y,Ha CW,Kim JH,Chun JSdoi
10.1136/annrheumdis-2015-208406subject
Has Abstractpub_date
2016-11-01 00:00:00pages
2045-2052issue
11eissn
0003-4967issn
1468-2060pii
annrheumdis-2015-208406journal_volume
75pub_type
杂志文章abstract:OBJECTIVE:To evaluate changes in baseline patient characteristics and entry criteria of randomised, controlled studies of tumour necrosis factor alpha (TNFα) inhibitors in rheumatoid arthritis (RA) patients. METHODS:A systematic literature review was performed using predefined inclusion criteria to identify randomised...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.2010.146043
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND:Physical disability is part of the end point measures in rheumatoid arthritis clinical trials. The Stanford Health Assessment Questionnaire Disability Index (HAQ DI) is often used for this purpose but lacks international uniformity owing to variations in the translated and adapted questionnaires and variatio...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:
更新日期:2001-09-01 00:00:00
abstract:BACKGROUND:Since approval of tocilizumab (TCZ) for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), interleukin 6 (IL-6) pathway inhibition was evaluated in trials of TCZ and other agents targeting the IL-6 receptor and ligand in various RA populations and other inflammatory diseases. Thi...
journal_title:Annals of the rheumatic diseases
pub_type: 共识发展会议,杂志文章
doi:10.1136/annrheumdis-2012-202469
更新日期:2013-04-01 00:00:00
abstract::Rheumatoid arthritis (RA) is diagnosed based on phenotypic characteristics. The 2010 ACR/EULAR criteria were derived with the aim of classifying RA earlier in the disease course than the 1987 ACR criteria. When reviewing thus far published validation studies, it is clear that the 2010 criteria can be fulfilled earlier...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2012-201426
更新日期:2012-10-01 00:00:00
abstract::There is no agreement as to which variable best mirrors disease activity in rheumatoid arthritis (RA) and no studies have been performed on the validity of disease activity variables. In this study the validity of 10 commonly used single variables and three composite indices was tested. All patients participated in a ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.51.2.177
更新日期:1992-02-01 00:00:00
abstract:OBJECTIVE:Previously an upregulation of E-cadherin and its associated molecules alpha-catenin, beta-catenin and plakoglobin has been demonstrated in clinically overt inflammatory bowel disease (IBD). The aim of this study was to investigate the expression of the E-cadherin/catenin complex in subclinically inflamed bowe...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.59.3.211
更新日期:2000-03-01 00:00:00
abstract:OBJECTIVE:To evaluate salivary hyaluronic acid (HA) concentration in patients with primary Sjögren's syndrome (SS). METHODS:Salivary and serum HA concentrations were evaluated using a radiometric assay. Thirty nine patients with SS served as the study group and their results were compared with 19 patients having clini...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.57.8.506
更新日期:1998-08-01 00:00:00
abstract:OBJECTIVE:A study was undertaken to investigate the in vivo pathogenic role of Toll-like receptor 4 (TLR-4) in the antiphospholipid syndrome (APS) by studying the thrombogenic antiphospholipid (aPL) activity in lipopolysaccharide (LPS) non-responsive (LPS-/-) mice and the association between tlr4 gene polymorphisms and...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2006.065037
更新日期:2007-10-01 00:00:00
abstract:OBJECTIVES:To examine the long term prognosis in patients with fibromyalgia (FM). METHODS:Forty five of 70 patients who had participated in a three week trial six years earlier completed again the same questionnaires used previously. RESULTS:Most symptoms had remained stable. Pain had increased, but some aspects of q...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.61.7.644
更新日期:2002-07-01 00:00:00
abstract::Leishmaniasis is an intracellular protozoan infection that can lead to cutaneous, mucocutaneous, visceral or systemic manifestations depending on the parasite species and virulence and on the host immune response. It is endemic in countries of Europe (Mediterranean basin), Asia, Africa, Central and South America, but ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/annrheumdis-2011-200596
更新日期:2012-04-01 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:OBJECTIVES:To investigate whether anti-Saccharomyces cerevisiae antibodies (ASCA), a marker for Crohn's disease (CD), are present in spondyloarthropathies (SpA) and in the subgroups ankylosing spondylitis (AS), undifferentiated SpA (uSpA), and psoriatic arthritis (PsA), in comparison with healthy and inflammatory contr...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.62.5.455
更新日期:2003-05-01 00:00:00
abstract:OBJECTIVE:To define the role of ultrasound (US) for the assessment of patients with rheumatoid arthritis (RA) in clinical remission, including joint and tendon evaluation. METHODS:A multicentre longitudinal study has been promoted by the US Study Group of the Italian Society for Rheumatology. 25 Italian centres partic...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/annrheumdis-2018-213217
更新日期:2018-09-01 00:00:00
abstract::The relation between common rheumatic diseases such as osteoarthrosis, arthralgia without definite signs of osteoarthrosis, subacromial shoulder pain, different forms of tendinitis, low back pain and neck pain, and the level of formal education, occupational workload and some lifestyle factors were examined in 502 of ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.51.7.835
更新日期:1992-07-01 00:00:00
abstract::A method is described for evaluating the progress of patients with back pain. Various symptoms were scored on analogue scales and spinal motion was measured by various techniques. These data were integrated to make subjective and objective indices respectively. Reasonable reproducibility of the measurements was obtain...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1136/ard.40.5.449
更新日期:1981-10-01 00:00:00
abstract:OBJECTIVE:To investigate the sympathetic and parasympathetic cardiovascular function in primary Sjögren's syndrome (SS) and to investigate the possible relation with ocular dryness. METHODS:41 (40 women) patients with primary SS, mean age 50 years (range 20-80) with a mean disease duration of eight years (range 1-30),...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.58.12.746
更新日期:1999-12-01 00:00:00
abstract:OBJECTIVE:To study immunological markers and compare these markers with standard measures for the clinical and immunological follow up of vasculitis activity in hepatitis C virus (HCV) associated cryoglobulinaemic vasculitis (CV). METHODS:Serial serum samples from eight patients with newly diagnosed HCV associated CV ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.60.4.385
更新日期:2001-04-01 00:00:00
abstract:BACKGROUND:Rheumatoid factors (RFs) and antibodies against cyclic citrullinated peptides (CCPs) of IgG, IgA and IgM isotype have been shown to precede disease onset by years. OBJECTIVE:To evaluate serological risk markers in first-degree relatives from multicase families in relation to genetic and environmental risk f...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2011-200668
更新日期:2012-06-01 00:00:00
abstract:OBJECTIVE:To examine the effect of infliximab plus methotrexate (MTX) compared with placebo plus MTX on bone loss in patients with early rheumatoid arthritis (RA) in a double-blind randomised study design. Further, to explore the associations between bone loss and markers of RA disease. METHODS:All 20 patients with RA...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,随机对照试验
doi:10.1136/ard.2008.106484
更新日期:2009-12-01 00:00:00
abstract:OBJECTIVES:To identify predictors of clinical remission as well as of no x-ray progression in a cohort of early rheumatoid arthritis (ERA) treated with a tight-control protocol. METHODS:A total of 121 consecutive patients with ERA were treated to reach European League Against Rheumatism (EULAR) and/or American College...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章
doi:10.1136/ard.2010.142729
更新日期:2011-07-01 00:00:00
abstract:OBJECTIVE:To develop widely accepted international severity score for children and adult patients with familial Mediterranean fever (FMF) that can be easily applied, in research and clinical practice. METHODS:Candidate severity criteria were suggested by several FMF expert physicians. After three rounds of Delphi surv...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2015-208671
更新日期:2016-06-01 00:00:00
abstract::Expression of major histocompatibility complex (MHC) class II and other lymphocyte activation markers on peripheral blood and synovial fluid T lymphocytes from patients with rheumatoid arthritis (RA), psoriatic arthritis, and Reiter's syndrome were measured and the mean fluorescence intensities of these antigens were ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.49.2.81
更新日期:1990-02-01 00:00:00
abstract:OBJECTIVES:There are no agreed criteria for osteoarthritis (OA) of the knee in population studies. The radiographic scoring system of Kellgren and Lawrence has been the system most used in the past and although other methods have been developed, comparisons have not been performed. Therefore these grading systems were ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.52.11.790
更新日期:1993-11-01 00:00:00
abstract::One hundred consecutive admissions to an acute geriatric unit were examined for clinical and radiographic evidence of osteoarthritis (OA) and articular chondrocalcinosis (ACC). Thirty-four patients had ACC. This was age related, the prevalence rising from 15% in patients aged 65-74 years to 44% in patients over 84 yea...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.42.3.280
更新日期:1983-06-01 00:00:00
abstract:OBJECTIVES:The relationship between radiographic evidence of osteoarthritis and knee pain has been weak. This may be because features that best discriminate knees with pain have not been included in analyses. We tested the correlation between knee pain and radiographic features taking into account both image analysis f...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/annrheumdis-2018-213492
更新日期:2018-11-01 00:00:00
abstract:OBJECTIVE:To investigate the role of CD8 cell subsets in the pathogenesis of rheumatoid arthritis (RA) and the phenotypes of T cells adherent or non-adherent to the target cells (endothelial cells and synovial cells) pre-treated with IL-1 beta. METHODS:The expression of S6F1 on CD8 cells and that of an activation mark...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.53.12.816
更新日期:1994-12-01 00:00:00
abstract:OBJECTIVES:To study the reliability and construct validity of ultrasound in interphalangeal finger joints affected by erosive osteoarthritis (EOA) and non-EOA with MRI as the reference method. METHODS:252 joints were examined by ultrasound, conventional radiography and clinical examination. Ultrasound was performed us...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2010.134932
更新日期:2011-02-01 00:00:00
abstract::An investigation of cell-mediated cytotoxicity in 22 patients with systemic lupus erythematosus (SLE), using both whole blood and purified peripheral blood mononuclear cells (PBM) to measure antibody-dependent (ADCC) and phytohaemagglutinin (PHA)-induced lymphocyte cytotoxicity for Chang liver cells, has revealed 2 di...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.40.1.11
更新日期:1981-02-01 00:00:00
abstract::Chemotactic migration of leucocytes largely depends on adhesive interaction with the substratum and recognition of a chemoattractant gradient. Both aspects, cell adhesion and chemotaxis, are regulated by members of the family of chemotactic cytokines (chemokines) comprising structurally related and secreted proteins o...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.2004.028316
更新日期:2004-11-01 00:00:00
abstract:OBJECTIVE:To investigate the inflammatory response in giant cell arteritis (GCA) by characterising the DNA methylation pattern within the temporal artery microenvironment. METHODS:Twelve patients with non-equivocal histological evidence for GCA and 12 age-matched, sex-matched and ethnicity-matched controls with normal...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2014-207116
更新日期:2016-06-01 00:00:00