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-antiangiogenic protein (DAAP), which can both bind VEGF-A and angiopoietins and block their actions. This study was performed to evaluate the antiarthritic effect of DAAP and the combination effect with the tumor necrosis factor α (TNF-α) inhibitor in collagen-induced arthritis (CIA). METHODS:Recombinant DAAP, VEGF-Trap, Tie2-Fc and dimeric Fc proteins were produced and purified from CHO cells in large-scale bioreactors. CIA was induced in DBA/1 mice with type II collagen. The preventive effect of DAAP was determined and compared with other decoy receptors such as VEGF-Trap or Tie2-Fc, which block VEGF-A or angiopoietins, respectively. The clinical, radiographic, pathologic and immunohistochemical analyses were performed in CIA mice. The levels of matrix metalloprotease 3 (MMP-3) and interleukin 1β (IL-1β) were quantified by enzyme-linked immunosorbent assay, and receptor activator of nuclear factor κB ligand (RANKL) mRNA levels were measured by polymerase chain reaction. Finally, we investigated the combination effects of DAAP with a low dose of TNF-α decoy receptor (etanercept 10 mg/kg). RESULTS:On the basis of clinical and radiographic evaluation, DAAP had a much greater inhibitory effect than VEGF-Trap or Tie2-Fc on arthritis severity and bone destruction. These inhibitory effects were accompanied by significantly diminishing pathologic abnormalities, CD31-positive vasculature and synovial infiltration by F4/80-positive macrophages. The levels of MMP-3, IL-1β and RANKL were much lower in the DAAP-injected group than those of the control. Furthermore, DAAP showed a therapeutic effect and a combination effect with etanercept when injected after arthritis onset in established CIA. CONCLUSIONS:DAAP has not only potent prophylactic effects on both inflammation and bone destruction but also therapeutic effects, alone and in combination with a TNF-α inhibitor in CIA mice. These results suggest that DAAP could be used as an effective new therapeutic agent for RA.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Hah YS,Koh YJ,Lim HS,Kim HO,Cheon YH,Noh HS,Jang KY,Lee SY,Lee GM,Koh GY,Lee SIdoi
10.1186/ar4265subject
Has Abstractpub_date
2013-08-14 00:00:00pages
R85issue
4eissn
1478-6354issn
1478-6362pii
ar4265journal_volume
15pub_type
杂志文章abstract::Rheumatoid arthritis (RA) is a systemic autoimmune disease manifesting in joint destruction. The recognized hallmark of RA pathogenesis is the involvement of immune cells which produce many mediators potentiating an inflammatory environment. RA synovial fibroblasts (RASFs) contribute significantly to disease progressi...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/s13075-015-0846-4
更新日期:2015-11-06 00:00:00
abstract:INTRODUCTION:Rituximab (RTX) therapy of rheumatoid arthritis (RA) exhibits enhanced effectiveness in seropositive patients. Using patient sera, we tested if this improved efficacy was associated with enhanced RTX mediated complement-dependent cytotoxicity (RTX-CDC). METHODS:We developed an in vitro assay for RTX-CDC u...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4152
更新日期:2013-01-25 00:00:00
abstract:BACKGROUND:Stem cell therapy is considered as a promising alternative to treat intervertebral disc degeneration (IDD). Extensive work had been done on identifying and comparing different types of candidate stem cells, both in vivo and in vitro. However, few studies have shed light on degenerative nucleus pulposus cells...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1677-x
更新日期:2018-08-16 00:00:00
abstract::Anti-glucose-6-phosphate isomerase (GPI) antibodies are known to be arthritogenic autoantibodies in K/BxN mice, although some groups have reported that few healthy humans retain these antibodies. The expression of Fcgamma receptors (FcgammaRs) is genetically regulated and has strong implications for the development of...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1802
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Cartilage damage impacts on patient disability in rheumatoid arthritis (RA). The aims of this magnetic resonance imaging (MRI) study were to investigate cartilage damage over three years and determine predictive factors. METHODS:A total of 38 RA patients and 22 controls were enrolled at t = 0 (2009). Afte...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4462
更新日期:2014-01-30 00:00:00
abstract:INTRODUCTION:Broad-range rDNA PCR provides an alternative, cultivation-independent approach for identifying bacterial DNA in reactive and other form of arthritis. The aim of this study was to use broad-range rDNA PCR targeting the 16S rRNA gene in patients with reactive and other forms of arthritis and to screen for th...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2748
更新日期:2009-01-01 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::We investigated the therapeutic potential and mechanism of action of IFN-beta protein for the treatment of rheumatoid arthritis (RA). Collagen-induced arthritis was induced in DBA/1 mice. At the first clinical sign of disease, mice were given daily injections of recombinant mouse IFN-beta or saline for 7 days. Disease...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1165
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Here we integrate verified signals from previous genetic association studies with gene expression and pathway analysis for discovery of new candidate genes and signaling networks, relevant for rheumatoid arthritis (RA). METHOD:RNA-sequencing-(RNA-seq)-based expression analysis of 377 genes from previously v...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1220-5
更新日期:2017-02-02 00:00:00
abstract:BACKGROUND:Reactive oxygen species (ROS) regulate the migration and invasion of fibroblast-like synoviocytes (FLS), which are key effector cells in rheumatoid arthritis (RA) pathogenesis. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) induces ROS generation and, consequently, enhances cell migration. Desp...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02204-0
更新日期:2020-05-15 00:00:00
abstract::Osteoporosis results from a loss of bone mass and bone structure such that the bone becomes weak and fractures with very little trauma. Until recently, the approved osteoporosis therapies prevented more bone loss by altering osteoclast activity and lifespan. Recently, attention has turned away from osteoclast inhibiti...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar797
更新日期:2003-01-01 00:00:00
abstract::Established rheumatoid arthritis (RA) is associated with a doubled cardiovascular risk. However, data about the cardiovascular risk in early RA are scarce. Preclinical atherosclerosis can be reliably assessed with the carotid intima media thickness (cIMT), and the cIMT is a well-validated predictor of cardiovascular e...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar3126
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Inhibitor of DNA binding 1 (Id1) is a nuclear protein containing a basic helix-loop-helix (bHLH) domain that regulates cell growth by selective binding and prevention of gene transcription. Sources of Id1 production in rheumatoid arthritis synovial tissue (RA ST) and its range of functional effects in RA rem...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0984-3
更新日期:2016-04-12 00:00:00
abstract:BACKGROUND:Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint stiffness, finally leading to tissue destruction. Connective tissue growth factor (CTGF) is a critical factor in RA progression, which promotes fibroblast-like synoviocyte (FLS) proliferation, pannus formation, ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-2133-2
更新日期:2020-03-27 00:00:00
abstract:BACKGROUND:Proprotein convertase subtilisin kexin 9 (PCSK9) targets the LDL-receptor (LDLR) which raises LDL-levels. In addition, PCSK9 has proinflammatory immunological effects. Here, we investigate the role of PCSK9 in relation to the inflammatory activity in patients with rheumatoid arthritis (RA). METHODS:PCSK9-le...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02386-7
更新日期:2021-01-19 00:00:00
abstract:INTRODUCTION:In the present systematic review and meta-analysis, we assessed the effectiveness of different forms of balneotherapy (BT) and hydrotherapy (HT) in the management of fibromyalgia syndrome (FMS). METHODS:A systematic literature search was conducted through April 2013 (Medline via Pubmed, Cochrane Central R...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1186/ar4603
更新日期:2014-07-07 00:00:00
abstract::The initiation of an immune response requires that professional antigen-presenting cells, such as dendritic cells, physically interact with antigen-specific T cells within the complex environment of the lymph node. Although the way in which antigen is presented to T cells and in particular the cellular associations in...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1843
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Comorbidities may contribute to disease activity and treatment response in rheumatoid arthritis (RA) patients. We defined a somatization comorbidity phenotype (SCP) and examined its influence on response to certolizumab pegol (CZP) using data from the PREDICT trial. METHODS:Patients in PREDICT were randomiz...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-017-1412-z
更新日期:2017-09-29 00:00:00
abstract:INTRODUCTION:Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent self-limiting fever and serositis that mainly affects Mediterranean populations. Many patients with FMF have been reported in Japan due to increasing recognition of this condition and the availability of ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-014-0439-7
更新日期:2014-09-27 00:00:00
abstract::With little in the way of effective therapeutic strategies to target the innate immune response, a better understanding of the critical pathways regulating neutrophil and macrophage responses in inflammation is key to the development of novel therapies. Hypoxia inducible factor (HIF) was originally identified as a cen...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2632
更新日期:2009-01-01 00:00:00
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::A considerable amount of research time has been invested in studies aimed at elucidating pathogenic processes in systemic sclerosis (SSc). Despite this, major challenges for biomedical science remain, such as identification of the key factors that determine susceptibility to SSc, and elucidation of the precise nature ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2186
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Ultrasound (US) is a sensitive method for detecting joint/tendon inflammation in patients with rheumatoid arthritis (RA). Subclinical inflammation is often found in patients with RA in composite score remission. The purpose of the present study was to explore whether US of only the hands is sufficient to ide...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1428-4
更新日期:2017-10-04 00:00:00
abstract:BACKGROUND:The aims of the present study were to determine the relationship between bone destruction and bone formation in the delayed-type hypersensitivity arthritis (DTHA) model and to evaluate the effect of receptor activator of nuclear factor κB ligand (RANKL) blockade on severity of arthritis, bone destruction, an...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0931-3
更新日期:2016-01-23 00:00:00
abstract:BACKGROUND:The idiopathic inflammatory myopathies (IIM) are autoimmune diseases characterised by acquired proximal muscle weakness, inflammatory cell infiltrates in muscle and myositis-specific/associated autoantibodies. It is unclear which pathways are involved in IIM, and the functional relationship between autoantib...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1061-7
更新日期:2016-07-07 00:00:00
abstract:BACKGROUND:Factors associated with care concordant with the American College of Rheumatology (ACR) recommendations for the use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) are unknown. METHODS:We identified a national cohort of biologic-naive patients with RA with visits between Decem...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0992-3
更新日期:2016-04-26 00:00:00
abstract:BACKGROUND:Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs (circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases. However, the role of circRNA in lupus nephritis has bee...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02404-8
更新日期:2021-01-13 00:00:00
abstract:INTRODUCTION:Progressive fibrosis in systemic sclerosis (SSc) is linked to aberrant transforming growth factor beta (TGF-beta) signaling. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) blocks fibrogenic TGF-beta responses in vitro and in vivo. Reduced expression and function of PPAR-gamma in patients wit...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3827
更新日期:2012-05-01 00:00:00
abstract:BACKGROUND:Pepsin agglutinators, discovered over 50 years ago, have been recently referred to as anti-hinge antibodies (AHAs) because of their reaction with the IgG hinge epitope. AHAs have different reactivity for each hinge epitope generated by each protease that cleaves the hinge region at different sites. Moreover,...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02251-7
更新日期:2020-06-26 00:00:00
abstract::Historically, the osteoblast has been considered the master cell in the control of osteoclast development and, therefore, bone resorption. Now the interactions between cells of the immune system and bone cells have redefined our thinking on the regulation of bone resorption. Moreover, the crosstalk between these cell ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2141
更新日期:2007-01-01 00:00:00