Abstract:
:The mechanism of endothelin-1 (ET-1)-induced nitric oxide (NO) production, MMP-1 production and MMP-13 production was investigated in human osteoarthritis chondrocytes. The cells were isolated from human articular cartilage obtained at surgery and were cultured in the absence or presence of ET-1 with or without inhibitors of protein kinase or LY83583 (an inhibitor of soluble guanylate cyclase and of cGMP). MMP-1, MMP-13 and NO levels were then measured by ELISA and Griess reaction, respectively. Additionally, inducible nitric oxide synthase (iNOS) and phosphorylated forms of p38 mitogen-activated protein kinase, p44/42, stress-activated protein kinase/Jun-N-terminal kinase and serine-threonine Akt kinase were determined by western blot. Results show that ET-1 greatly increased MMP-1 and MMP-13 production, iNOS expression and NO release. LY83583 decreased the production of both metalloproteases below basal levels, whereas the inhibitor of p38 kinase, SB202190, suppressed ET-1-stimulated production only. Similarly, the ET-1-induced NO production was partially suppressed by the p38 kinase inhibitor and was completely suppressed by the protein kinase A kinase inhibitor KT5720 and by LY83583, suggesting the involvement of these enzymes in relevant ET-1 signalling pathways. In human osteoarthritis chondrocytes, ET-1 controls the production of MMP-1 and MMP-13. ET-1 also induces NO release via iNOS induction. ET-1 and NO should thus become important target molecules for future therapies aimed at stopping cartilage destruction.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Manacu CA,Martel-Pelletier J,Roy-Beaudry M,Pelletier JP,Fernandes JC,Shipkolye FS,Mitrovic DR,Moldovan Fdoi
10.1186/ar1489keywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
R324-32issue
2eissn
1478-6354issn
1478-6362pii
ar1489journal_volume
7pub_type
杂志文章abstract:INTRODUCTION:Hyperuricemia is the greatest risk factor for gout and is caused by an overproduction and/or inefficient renal clearance of urate. The fractional renal clearance of urate (FCU, renal clearance of urate/renal clearance of creatinine) has been proposed as a tool to identify subjects who manifest inefficient ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/ar4020
更新日期:2012-08-17 00:00:00
abstract:INTRODUCTION:In cross-sectional studies, patients with rheumatoid arthritis (RA) have higher coronary artery calcium (CAC) than controls. However, their rate of progression of CAC and the predictors of CAC progression have heretofore remained unknown. METHODS:Incidence and progression of CAC were compared in 155 patie...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4314
更新日期:2013-09-25 00:00:00
abstract:BACKGROUND:Systemic sclerosis (SSc) is characterized by early vascular abnormalities and subsequent fibroblast activation to myofibroblasts, leading to fibrosis. Recently, endothelial-to-mesenchymal transition (EndoMT), a complex biological process in which endothelial cells lose their specific markers and acquire a me...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1122-y
更新日期:2016-10-06 00:00:00
abstract:INTRODUCTION:Soft tissue knee injury is a well-established and potent risk factor for development of knee osteoarthritis. However, there is a paucity of epidemiological data from the general population. Our aim was to estimate the annual person-level incidence for a wide spectrum of clinically diagnosed soft tissue kne...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4678
更新日期:2014-07-31 00:00:00
abstract:INTRODUCTION:TNFα is a proinflammatory cytokine that plays a central role in the pathogenesis of rheumatoid arthritis (RA). We investigated the effects of certolizumab pegol, a TNFα blocker, on endothelial cell function and angiogenesis. METHODS:Human dermal microvascular endothelial cells (HMVECs) were stimulated wit...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3812
更新日期:2012-04-25 00:00:00
abstract:INTRODUCTION:The important functions of the meniscus are shock absorption, passive stabilization and load transmission of the knee. Because of the avascularity of two-thirds of the meniscal center region, the treatment of tears in this area is hard. Recently, microRNAs have been proven to play an important role in the ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-014-0488-y
更新日期:2014-11-28 00:00:00
abstract::Autoantibodies to neutrophil cytoplasmic antigen-associated vasculitis (AAV) is characterised by inflammation of blood vessels. The introduction of immunosuppressive therapy with glucocorticoids and cyclophosphamide transformed AAV from a fatal condition to a largely treatable condition. Over the past 30 years, consid...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3797
更新日期:2012-04-30 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::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 henc...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2340
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:An adjuvanted pandemic H1N1 influenza (pH1N1) vaccine (Pandemrix) was reported as highly immunogenic resulting in seroconversion in 77 to 94% of adults after administration of a single dose. The aim of the study was to investigate the impact of different anti-rheumatic treatments on antibody response to pH...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4427
更新日期:2014-01-02 00:00:00
abstract:BACKGROUND:In some rheumatic diseases such as systemic lupus erythematosus (SLE), low serum complement ('hypocomplementaemia') is a feature of active disease. However, the role of hypocomplementaemia in systemic sclerosis (SSc) is unknown. We sought to determine the frequency, clinical associations and relationship to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1147-2
更新日期:2016-10-22 00:00:00
abstract::Idiopathic CD4 lymphocytopenia (ICL) is a presumed heterogenous syndrome with key element low CD4 T-cell counts (below 300/mm³) without evidence of HIV infection or other known immunodeficiency. The etiology, pathogenesis, and management of ICL remain poorly understood and inadequately defined. The clinical presentati...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4027
更新日期:2012-08-31 00:00:00
abstract:BACKGROUND:The information concerning non-invasive, easily obtainable, and accurate biomarkers for diagnosis of lupus nephritis (LN) is extremely limited. The aim of this study was to evaluate the diagnostic performance of cystatin C (CysC) and complement component 1q (C1q) for LN. METHODS:A case-control study that in...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2065-x
更新日期:2019-12-04 00:00:00
abstract:INTRODUCTION:Antibodies against citrullinated peptides (anti-CCP) and increased levels of cytokines precede the development of rheumatoid arthritis (RA) by several years. Recently, the proteins survivin and Fms-like tyrosine kinase 3 ligand (Flt3L) have been identified as biomarkers of RA associated with joint destruct...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4474
更新日期:2014-02-05 00:00:00
abstract:BACKGROUND:The aim was to further characterize immunoglobulin G4-related disease (IgG4-RD) by a large-scale multicenter study of its clinical and laboratory features conducted by multidisciplinary physicians of IgG4-RD in Japan. METHODS:Various specialists retrospectively evaluated IgG4-RD patients diagnosed between 1...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-017-1467-x
更新日期:2017-12-01 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::There has been some evidence that Behçet's disease (BD) has a significant autoimmune component but the molecular identity of putative autoantigens has not been well characterized. In the initial analysis of the autoantibody profile in 39 Chinese BD patients, autoantibodies to cellular proteins were uncovered in 23% as...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1798
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:It is known that anticitrullinated peptide antibody (ACPA)-positive rheumatoid arthritis (RA) has a preclinical phase. Whether this phase is also present in ACPA-negative RA is unknown. To determine this, we studied ACPA-negative arthralgia patients who were considered prone to progress to RA for local sub...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4536
更新日期:2014-04-10 00:00:00
abstract::As a consequence of the avascular nature of cartilage the microenvironment in which chondrocytes must exist is characterized by hostile conditions, most prominently very low levels of oxygen (hypoxia). In recent years, a vast number of papers reporting on the role of hypoxia in cartilage development and disease has be...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar1894
更新日期:2006-01-01 00:00:00
abstract::Collagen-induced arthritis (CIA), an approved animal model for rheumatoid arthritis, is thought to be a T cell-dependent disease. There is evidence that CD8+ T cells are a major subset controlling the pathogenesis of CIA. They probably contribute to certain features of disease, namely tissue destruction and synovial h...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1758
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Interleukin-17A (IL-17A) plays a pathogenic role in several rheumatic diseases including spondyloarthritis and, paradoxically, has been described to both promote and protect from bone formation. We therefore examined the effects of IL-17A on osteoblast differentiation in vitro and on periosteal bone formatio...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0998-x
更新日期:2016-05-10 00:00:00
abstract::The transcription factor STAT-1 (signal transducer and activator of transcription-1) plays a pivotal role in the expression of inflammatory gene products involved in the pathogenesis of arthritis such as various cytokines and the CD40/CD40 ligand (CD40/CD40L) receptor-ligand dyad. The therapeutic efficacy of a synthet...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1869
更新日期:2006-01-01 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:INTRODUCTION:Immunological studies of giant cell arteritis (GCA) suggest that a triggering antigen of unknown nature could generate a specific immune response. We thus decided to detect autoantibodies directed against endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in the serum of GCA patients and to i...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3388
更新日期:2011-06-28 00:00:00
abstract:INTRODUCTION:Properdin amplifies the alternative pathway of complement activation. In the present study, we evaluated its role in the development of collagen antibody-induced arthritis (CAIA). METHODS:Arthritis was induced by intraperitoneal injection of a collagen antibody cocktail into properdin-deficient (KO) and w...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3926
更新日期:2012-07-25 00:00:00
abstract:INTRODUCTION:Early degeneration of the intervertebral disc (IVD) involves a change in cellular differentiation from notochordal cells (NCs) in the nucleus pulposus (NP) to chondrocyte-like cells (CLCs). The purpose of this study was to investigate the gene expression profiles involved in this process using NP tissue fr...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4157
更新日期:2013-01-29 00:00:00
abstract:INTRODUCTION:Rheumatoid arthritis is an autoimmune arthritis characterized by joint destruction. Anti-citrullinated protein antibodies are pathologic in rheumatoid arthritis, but the role of the citrullinated proteins themselves is much less clear. Citrullination is the conversion of the arginine residues of a protein ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4083
更新日期:2012-11-05 00:00:00
abstract::The detection of autoantibodies in human sera is an important approach to the diagnosis and management of patients with autoimmune conditions. To meet market demands, manufacturers have developed a wide variety of easy to use and cost-effective diagnostic kits that are designed to detect a variety of human serum autoa...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar782
更新日期:2003-01-01 00:00:00
abstract:INTRODUCTION:The FMS-related tyrosine kinase 3 ligand (Flt3L)/CD135 axis plays a fundamental role in proliferation and differentiation of dendritic cells (DCs). As DCs play an important role in rheumatoid arthritis (RA) immunopathology we studied in detail the Flt3L/CD135 axis in RA patients. METHODS:The levels of Flt...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4403
更新日期:2013-01-01 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