Abstract:
OBJECTIVE:Progranulin (PGRN) was previously isolated as an osteoarthritis (OA)-associated growth factor. Additionally, PGRN was found to play a therapeutic role in inflammatory arthritis mice models through antagonising tumour necrosis factor α (TNF-α). This study was aimed at investigating the role of PGRN in degradation of cartilage and progression of OA. METHODS:Progression of OA was analysed in both spontaneous and surgically induced OA models in wild type and PGRN-deficient mice. Cartilage degradation and OA were evaluated using Safranin O staining, immunohistochemistry and ELISA. Additionally, mRNA expression of degenerative factors and catabolic markers known to be involved in cartilage degeneration in OA were analysed. Furthermore, the anabolic effects and underlying mechanisms of PGRN were investigated by in vitro experiments with primary chondrocytes. RESULTS:Here, we found that deficiency of PGRN led to spontaneous OA-like phenotype in 'aged' mice. Additionally, PGRN-deficient mice exhibited exaggerated breakdown of cartilage structure and OA progression, while local delivery of recombinant PGRN protein attenuated degradation of cartilage matrix and protected against OA development in surgically induced OA models. Furthermore, PGRN activated extracellular signal-regulated kinases (ERK) 1/2 signalling and elevated the levels of anabolic biomarkers in human chondrocyte, and the protective function of PGRN was mediated mainly through TNF receptor 2. Additionally, PGRN suppressed inflammatory action of TNF-α and inhibited the activation of β-Catenin signalling in cartilage and chondrocytes. CONCLUSIONS:Collectively, this study provides new insight into the pathogenesis of OA, and also presents PGRN as a potential target for the treatment of joint degenerative diseases, including OA.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Zhao YP,Liu B,Tian QY,Wei JL,Richbourgh B,Liu CJdoi
10.1136/annrheumdis-2014-205779subject
Has Abstractpub_date
2015-12-01 00:00:00pages
2244-2253issue
12eissn
0003-4967issn
1468-2060journal_volume
74pub_type
杂志文章abstract::Four patients with Neisseria meningitidis infection complicated by arthritis are described. Three patients had an acute polyarthritis which responded quickly to antimicrobial therapy. A fourth patient developed a prolonged arthritis which occurred after the initial infection had been successfully treated. Tenosynoviti...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.44.11.790
更新日期:1985-11-01 00:00:00
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::This article gives a short overview of the development and characteristics of the OMERACT rheumatoid arthritis MRI scoring system (RAMRIS), followed by an introduction to the use of the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. With this atlas, MRIs of wrist and metacarpophalangeal joints of patien...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2004.031773
更新日期:2005-02-01 00:00:00
abstract:OBJECTIVES:To assess the safety of intra-articular (IA) autologous tolerogenic dendritic cells (tolDC) in patients with inflammatory arthritis and an inflamed knee; to assess the feasibility and acceptability of the approach and to assess potential effects on local and systemic disease activities. METHODS:An unblinded...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,随机对照试验
doi:10.1136/annrheumdis-2015-208456
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Tumour necrosis factor alpha (TNFalpha) blockade using infliximab, a chimeric anti-TNFalpha antibody, is an effective treatment for both psoriasis and psoriatic arthritis (PsA). OBJECTIVE:To analyse the early effects of infliximab treatment on serial skin and synovial tissue biopsy samples. METHODS:Twelve ...
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.2003.018085
更新日期:2004-07-01 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:BACKGROUND:The threshold for disease activity required to start antitumour necrosis factor (TNF) therapy has been arbitrarily set in patients with axial spondyloarthritis (axSpA) at Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4. How this relates to spinal inflammation is unknown. OBJECTIVE:To systema...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2011-200508
更新日期:2012-07-01 00:00:00
abstract:OBJECTIVES:Reduced caveolin-1 levels in lung fibroblasts from patients with scleroderma and the lungs of bleomycin-treated mice promote collagen overexpression and lung fibrosis. This study was undertaken to determine whether caveolin-1 is deficient in leucocytes from bleomycin-treated mice and patients with scleroderm...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2009.117580
更新日期:2010-06-01 00:00:00
abstract:OBJECTIVE:Domains identified as a result of qualitative research and Delphi exercises to assess rheumatoid arthritis (RA) flare include pain, function, swollen and tender joints, patient and physician global, laboratory measures, participation, stiffness, self-management and fatigue. Here we examine aspects of construc...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/annrheumdis-2013-203496
更新日期:2014-10-01 00:00:00
abstract:OBJECTIVE:High serum interferon α (IFNα) activity is a heritable risk factor for systemic lupus erythematosus (SLE). Auto-antibodies found in SLE form immune complexes which can stimulate IFNα production by activating endosomal Toll-like receptors and interferon regulatory factors (IRFs), including IRF5. Genetic variat...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2011-200463
更新日期:2012-03-01 00:00:00
abstract:OBJECTIVE:To determine if early MRI measures predict X-ray progression at 1 and 2 years in a large RA trial cohort. DESIGN:This study included 256 methotrexate (MTX)-naïve RA patients from a randomised placebo-controlled trial of golimumab (GO-BEFORE). MRIs of wrist and 2nd-5th metacarpophalangeal joints at 0, 12, 24,...
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-2013-203444
更新日期:2014-11-01 00:00:00
abstract::The effect of immune complexes (IC) isolated from systemic lupus erythematosus (SLE) sera with polyethylene glycol and gel filtration on the chemotaxis and Fc receptor function of healthy monocytes was examined. Even at a low protein concentration (1 microgram/ml = 1 mg/l) ICs inhibit monocyte chemotaxis. ICs from pat...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.43.5.729
更新日期:1984-10-01 00:00:00
abstract:OBJECTIVE:To investigate the association of a recently described classification of Human leukocyte antigen (HLA)-DRB1 shared epitope alleles with rheumatoid factors (RF) and anti-cyclic citrullinated peptide (CCP) production and radiological severity in rheumatoid arthritis (RA). METHODS:Patients with RA (n = 962) wer...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.075382
更新日期:2008-07-01 00:00:00
abstract:OBJECTIVES:The aim of this study was to evaluate serum interleukin (IL) 12 concentration in patients with juvenile chronic arthritis (JCA), according to disease subtype, activity, and duration. IL12 has been demonstrated to prime the selective expansion of T helper (Th) cells with a Th1-type pattern of cytokine product...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.57.7.425
更新日期:1998-07-01 00:00:00
abstract::Results are reported from the first prospective study of gout in New Zealand Maoris based on a sample of 388 males and 378 females. At baseline, high mean levels of serum uric acid (SUA) were found, 0.422 +/- 0.092 mmol/1 (7.05 +/- 1.54 mg/100 ml) in males and 0.350 +/- 0.091 mmol/1 (5.85 +/- 1.52 mg/100 ml) in female...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.37.5.466
更新日期:1978-10-01 00:00:00
abstract:OBJECTIVE:To carry out a critical appraisal of the literature in an attempt to assess the current value of synovial fluid (SF) analysis in the diagnosis of joint disease. METHODS:A literature search was undertaken using the Medline, Biomed, Bids, Pubmed, and Embase electronic databases using the keywords: synovial flu...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.61.6.493
更新日期:2002-06-01 00:00:00
abstract:OBJECTIVES:The prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases who are frequently treated with disease modifying therapies remains poorly understood. This meta-analysis aims to assess the prevalence and clinical outcomes of COVID-19 in autoimmune diseases. METHODS:Electronic databases...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2020-218946
更新日期:2020-10-13 00:00:00
abstract::The success of anti-tumour necrosis factor (TNF) treatment, either using antibodies or soluble receptors, has defined TNF as a major factor of the inflammatory response in rheumatoid arthritis (RA). As a result of this success, much attention has been devoted to understanding the molecular mechanisms by which TNF expr...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.59.suppl_1.i54
更新日期:2000-11-01 00:00:00
abstract:BACKGROUND:A disease activity-guided dose optimisation strategy of adalimumab or etanercept (TNFi (tumour necrosis factor inhibitors)) has shown to be non-inferior in maintaining disease control in patients with rheumatoid arthritis (RA) compared with usual care. However, the cost-effectiveness of this strategy is stil...
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-2015-208317
更新日期:2016-11-01 00:00:00
abstract:OBJECTIVE:To investigate the possibility of drug-free remission in patients with psoriatic arthritis (PsA) in continuous remission. METHODS:Prospective observational study in disease-modifying antirheumatic drug (DMARD)-treated PsA patients in continuous disease remission (no musculoskeletal symptoms, no or minimal sk...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204229
更新日期:2015-04-01 00:00:00
abstract::An 85 year old man with a longstanding history of non-tophaceous gout developed a single large tophus, unassociated with inflammation, on his paretic leg over a six week period following an acute hemiplegia. The rapidity of tophus formation, its localisation to the paretic limb, and the apparent blunting of the acute ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.52.4.308
更新日期:1993-04-01 00:00:00
abstract::Leucopenia appears to be a more frequent complication of sulphasalazine treatment in rheumatoid arthritis than in inflammatory bowel disease and poses a management problem. In this study leucopenia was found in 20 patients, 14 of whom were participating in prospective studies (252 patients), giving an incidence of 5.6...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.48.6.505
更新日期:1989-06-01 00:00:00
abstract::The case is described of a patient with scleromyxoedema with features typical of systemic sclerosis. The features were so characteristic that the disease was misdiagnosed as systemic sclerosis. A brief review of the association of the two diseases is given. ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.51.10.1159
更新日期:1992-10-01 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:OBJECTIVE:To evaluate the efficacy and safety of monotherapy with adalimumab in patients with RA for whom previous DMARD treatment has failed. METHODS:In a 26 week, double blind, placebo controlled, phase III trial, 544 patients with RA were randomised to monotherapy with adalimumab 20 mg every other week, 20 mg weekl...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1136/ard.2003.013052
更新日期:2004-05-01 00:00:00
abstract:OBJECTIVES:Annual echocardiography screening is widely used in scleroderma, but the utility of longitudinal assessment is unknown. We evaluated whether change in right ventricular systolic pressure (RVSP) was a risk factor for mortality and development of pulmonary arterial hypertension (PAH) in a cohort of scleroderma...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2012-201861
更新日期:2013-07-01 00:00:00
abstract::Sepsis is a severe complication of abdominal infections such as peritonitis and is associated with high mortality. Unfortunately, the molecular mechanisms controlling the development of sepsis are still incompletely understood. Interestingly, the interleukin (IL) 12 family member IL27 seems to play a key role in sepsi...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.2007.078337
更新日期:2007-11-01 00:00:00
abstract:OBJECTIVE:The British Society for Rheumatology Biologics Register (BSRBR) has collected data on adverse events including pregnancies in patients with rheumatoid arthritis treated with anti-tumour necrosis factor (anti-TNF) therapy. The purpose of this report is to summarise the pregnancy outcomes in women treated with ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2010.140822
更新日期:2011-05-01 00:00:00
abstract:OBJECTIVES:To examine objectively spatial patterns of osteophytes around the distal end of the femur and to identify distinct subgroups. METHODS:A sample of 107 human femora from a large skeletal population were selected for study. These femora included subjects with evidence of late stage osteoarthritis (that is, wit...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.59.7.513
更新日期:2000-07-01 00:00:00
abstract:BACKGROUND:Recently, an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) collaboration developed new classification criteria for rheumatoid arthritis (RA). OBJECTIVE:To evaluate the diagnostic and discriminative ability of these new criteria compared with the 1987 ACR criteria and the ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2010.148619
更新日期:2011-08-01 00:00:00