Abstract:
:The enzyme methionine aminopeptidase-2 (MetAP-2) is thought to play an important function in human endothelial cell proliferation, and as such provides a valuable target in both inflammation and cancer. Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased synovial vascularity, and hence is a potential therapeutic target for angiogenesis inhibitors. We examined the use of PPI-2458, a selective non-reversible inhibitor of MetAP-2, in disease models of RA, namely acute and chronic collagen-induced arthritis (CIA) in mice. Whilst acute CIA is a monophasic disease, CIA induced with murine collagen type II manifests as a chronic relapsing arthritis and mimics more closely the disease course of RA. Our study showed PPI-2458 was able to reduce clinical signs of arthritis in both acute and chronic CIA models. This reduction in arthritis was paralleled by decreased joint inflammation and destruction. Detailed mechanism of action studies demonstrated that PPI-2458 inhibited human endothelial cell proliferation and angiogenesis in vitro, without affecting production of inflammatory cytokines. Furthermore, we also investigated release of inflammatory cytokines and chemokines from human RA synovial cell cultures, and observed no effect of PPI-2458 on spontaneous expression of cytokines and chemokines, or indeed on the angiogenic molecule vascular endothelial growth factor (VEGF). These results highlight MetAP-2 as a good candidate for therapeutic intervention in RA.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Bainbridge J,Madden L,Essex D,Binks M,Malhotra R,Paleolog EMdoi
10.1186/ar2340subject
Has Abstractpub_date
2007-01-01 00:00:00pages
R127issue
6eissn
1478-6354issn
1478-6362pii
ar2340journal_volume
9pub_type
杂志文章abstract:INTRODUCTION:Rheumatoid arthritis (RA) is a chronic inflammatory and destructive disease of the joint. The synovial lining consists of two main types of cells: synovial fibroblasts and macrophages. The macrophage-derived cytokine TNFα stimulates RA synovial fibroblasts to proliferate and produce growth factors, chemoki...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3778
更新日期:2012-03-14 00:00:00
abstract:BACKGROUND:Metformin could activate adenosine monophosphate-activated protein kinase (AMPK) which was postulated as a potential therapeutic target for osteoarthritis. This study aimed to examine the effects of metformin on cartilage and pain in osteoarthritis mouse model. METHODS:Eighty 10-week-old male C57BL/6 mice w...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-2129-y
更新日期:2020-02-22 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::Glucosamine in its acetylated form is a natural constituent of some glycosaminoglycans (for example, hyaluronic acid and keratan sulfate) in the proteoglycans found in articular cartilage, intervertebral disc and synovial fluid. Glucosamine can be extracted and stabilized by chemical modification and used as a drug or...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3657
更新日期:2012-01-30 00:00:00
abstract:INTRODUCTION:There is a suspicion of increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferations in patients with inflammatory arthritides receiving immunosuppressive drugs. We investigated the EBV load and EBV-specific T-cell response in patients treated with methotrexate (MTX) or anti-TNF therapy. MET...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2708
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Low-intensity pulsed ultrasound (LIPUS) has been known to promote bone healing by nonthermal effects. In recent studies, LIPUS has been shown to reduce inflammation in injured soft tissues. Xerostomia is one of the most common symptoms in Sjögren syndrome (SS). It is caused by a decrease in the quantity or...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0798-8
更新日期:2015-10-07 00:00:00
abstract:BACKGROUND:Autoreactive B cells are crucial players in the pathogenesis of rheumatoid arthritis (RA). Autoantibodies specific for citrullinated proteins (ACPA), present in the serum of approximately 60-70 % of patients, have a pathogenic role in the disease. B cell depleting therapies may result in a transient immunosu...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0918-0
更新日期:2016-01-16 00:00:00
abstract:BACKGROUND:Arhalofenate acid, the active acid form of arhalofenate, is a non-agonist peroxisome proliferator-activated receptor γ (PPARγ) ligand, with uricosuric activity via URAT1 inhibition. Phase II studies revealed decreased acute arthritis flares in arhalofenate-treated gout compared with allopurinol alone. Hence,...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1699-4
更新日期:2018-09-06 00:00:00
abstract:RESULTS:Anti-CarP antibodies were detected in 117 patients with RA (37.9%), ACPA in 190 patients (61.4%) and RF in 202 patients (65.3%). Two (2.04%) of the NHS were positive for anti-CarP, one NHS (1.02%) was positive for ACPA and three NHS were positive for RF (3.06%). Among disease controls, anti-CarP antibodies were...
journal_title:Arthritis research & therapy
pub_type: 已发布勘误
doi:10.1186/s13075-016-1205-9
更新日期:2016-12-16 00:00:00
abstract:INTRODUCTION:The present study aimed to explore a possible role for IL-21 producing Th-cells in the immunopathogenesis of granulomatosis with polyangiitis (GPA). METHODS:Peripheral blood from 42 GPA patients in remission and 29 age-matched healthy controls (HCs) were stimulated in vitro, and the frequencies of IL-21 p...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4247
更新日期:2013-01-01 00:00:00
abstract::Over the last decades, genetic factors for rheumatoid diseases like the HLA haplotypes have been studied extensively. However, during the past years of research, it has become more and more evident that the influence of epigenetic processes on the development of rheumatic diseases is probably as strong as the genetic ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2500
更新日期:2008-01-01 00:00:00
abstract::There has been a therapeutic revolution in rheumatology over the past 15 years, characterised by a move away from oral immuno-suppressive drugs toward parenteral targeted biological therapies. The potency and relative safety of the newer agents has facilitated a more aggressive approach to treatment, with many more pa...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2594
更新日期:2009-01-01 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:INTRODUCTION:The arthritis-specific Work Productivity Survey (WPS) was developed to evaluate productivity limitations associated with arthritis within and outside the home. There is an unmet need for an instrument assessing similar productivity limitations in axial spondyloarthritis (axSpA), including nonradiographic a...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/ar4680
更新日期:2014-08-06 00:00:00
abstract:BACKGROUND:The anti-cyclic citrullinated peptide (CCP) antibody is a diagnostic biomarker of rheumatoid arthritis (RA). However, some non-RA connective tissue disease (CTD) patients also test positive for the anti-CCP antibody and, thus, may ultimately develop RA. We retrospectively investigated whether anti-CCP-positi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02351-4
更新日期:2020-10-19 00:00:00
abstract:BACKGROUND:Interstitial lung disease in systemic sclerosis (SSc-ILD) is a major cause of SSc-related death. Imunosuppressive treatment (IS) is used in patients with SSc for various organ manifestations mainly to ameliorate progression of SSc-ILD. Data on everyday IS prescription patterns and clinical courses of lung fu...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1517-z
更新日期:2018-01-30 00:00:00
abstract:INTRODUCTION:Objectives were to investigate whether interactions between human osteoarthritic chondrocytes and 4-hydroxynonenal (HNE)-modified type II collagen (Col II) affect cell phenotype and functions and to determine the protective role of carnosine (CAR) treatment in preventing these effects. METHODS:Human Col I...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3173
更新日期:2010-01-01 00:00:00
abstract::Interstitial lung disease is a common manifestation of autoimmune myositis that confers significant morbidity and mortality. The vulnerability of the lung may offer insight into the etiology of this autoimmune disease. The frequency and patterns of lung injury vary based on the autoantibody. Antibodies against the ami...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3347
更新日期:2011-07-13 00:00:00
abstract:INTRODUCTION:Angiogenesis plays a critical role in synovial inflammation and joint destruction in rheumatoid arthritis (RA). Vascular endothelial growth factor A (VEGF-A) and angiopoietins are two important mediators of synovial angiogenesis. We have previously developed a novel chimeric decoy receptor, namely, double-...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4265
更新日期:2013-08-14 00:00:00
abstract:INTRODUCTION:The objective was to characterize the clinical and myopathologic features of patients with scleroderma-polymyositis (SSc-PM) overlap compared with a population of patients with systemic sclerosis (SSc) and polymyositis (PM). METHODS:A three-way comparison of patients with SSc-PM overlap (n = 25) with pati...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4562
更新日期:2014-05-13 00:00:00
abstract:INTRODUCTION:The immunoregulatory function of interleukin (IL)-29 has recently been recognized. However, little is known about the involvement of IL-29 in the pathogenesis of rheumatoid arthritis (RA). This study aimed to examine the expression profiles of IL-29 in blood, synovial fluid (SF) and synovium in RA patients...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4067
更新日期:2012-10-19 00:00:00
abstract:BACKGROUND:Synovial fibroblasts play a key role in joint destruction and regulation of the inflammatory infiltrate in established rheumatoid arthritis (RA). The mechanisms by which this occurs in the earliest stages of RA are largely unknown. We investigated the role of Dickkopf-related protein 1 (DKK1) produced by syn...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0915-3
更新日期:2016-01-19 00:00:00
abstract::Members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family are known to influence development, angiogenesis, coagulation and progression of arthritis. As proteinases their substrates include the von Willebrand factor precursor and extracellular matrix components such as procollagen, ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1783
更新日期:2005-01-01 00:00:00
abstract::As translational clinical researchers familiar with the risk-benefit of hematopoietic stem cell transplantation in autoimmune diseases, we are intrigued by the recent report of umbilical cord mesenchymal stem cell (UC-MSC) transplantation in treatment-refractory systemic lupus erythematosus nephritis by Wang and colle...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar4677
更新日期:2014-07-30 00:00:00
abstract:BACKGROUND:Established rheumatoid arthritis (RA) patients display differentially expressed genes coding for cytokine/chemokine-mediated immunity compared to healthy controls. It is unclear, however, if in the pre-arthritis phase of clinically suspect arthralgia (CSA) expression of immune genes differ between patients w...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02361-2
更新日期:2020-11-09 00:00:00
abstract::Ankylosing spondylitis (AS) is a member of the family of spondyloarthropathies, which are inflammatory arthritides largely involving the axial skeleton and commonly accompanied by peripheral arthritis. Genetic factors, particularly the presence of HLA-B27, are major contributors to the susceptibility for AS. Despite s...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1012
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Evidence suggests lymphatic function mediates local rheumatoid arthritis (RA) flares. Yet biologics that target the immune system are dosed systemically via the subcutaneous (SC) administration route, thereby inefficiently reaching local lymphatic compartments. Nanotopography has previously been shown to dis...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1323-z
更新日期:2017-05-31 00:00:00
abstract:INTRODUCTION:Lesional skin of patients with discoid lupus erythematosus (DLE) contains macrophages, whose polarization has yet to be investigated. To test our hypothesis that M1 macrophages would be increased in DLE skin, we examined transcriptome alterations in immune cell gene expression and macrophage features in DL...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0839-3
更新日期:2015-11-13 00:00:00
abstract::Mammalian immune responses are intended to eradicate microbial pathogens and thus protect individuals from the harmful effects of such infections. However, unresolved inflammation can be devastating to the host and cause tissue damage and organ malfunction. Immune responses can even mistakenly target self-antigens and...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4131
更新日期:2013-01-25 00:00:00
abstract:BACKGROUND:RA and CVD both have inflammation as part of the underlying biology. Our objective was to explore the relationships of GlycA, a measure of glycosylated acute phase proteins, with inflammation and cardiometabolic risk in RA, and explore whether these relationships were similar to those for persons without RA....
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0982-5
更新日期:2016-04-12 00:00:00