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 II was treated with HNE at different molar ratios (MR) (1:20 to 1:200; Col II:HNE). Articular chondrocytes were seeded in HNE/Col II adduct-coated plates and incubated for 48 hours. Cell morphology was studied by phase-contrast and confocal microscopy. Adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and α1β1 integrin at protein and mRNA levels were quantified by Western blotting, flow cytometry and real-time reverse transcription-polymerase chain reaction. Cell death, caspases activity, prostaglandin E2 (PGE2), metalloproteinase-13 (MMP-13), mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) were assessed by commercial kits. Col II, cyclooxygenase-2 (COX-2), MAPK, NF-κB-p65 levels were analyzed by Western blotting. The formation of α1β1 integrin-focal adhesion kinase (FAK) complex was revealed by immunoprecipitation. RESULTS:Col II modification by HNE at MR approximately 1:20, strongly induced ICAM-1, α1β1 integrin and MMP-13 expression as well as extracellular signal-regulated kinases 1 and 2 (ERK1/2) and NF-κB-p65 phosphorylation without impacting cell adhesion and viability or Col II expression. However, Col II modification with HNE at MR approximately 1:200, altered chondrocyte adhesion by evoking cell death and caspase-3 activity. It inhibited α1β1 integrin and Col II expression as well as ERK1/2 and NF-κB-p65 phosphorylation, but, in contrast, markedly elicited PGE2 release, COX-2 expression and p38 MAPK phosphorylation. Immunoprecipitation assay revealed the involvement of FAK in cell-matrix interactions through the formation of α1β1 integrin-FAK complex. Moreover, the modification of Col II by HNE at a 1:20 or approximately 1:200 MR affects parameters of the cell shape. All these effects were prevented by CAR, an HNE-trapping drug. CONCLUSIONS:Our novel findings indicate that HNE-binding to Col II results in multiple abnormalities of chondrocyte phenotype and function, suggesting its contribution in osteoarthritis development. CAR was shown to be an efficient HNE-snaring agent capable of counteracting these outcomes.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
El-Bikai R,Welman M,Margaron Y,Côté JF,Macqueen L,Buschmann MD,Fahmi H,Shi Q,Maghni K,Fernandes JC,Benderdour Mdoi
10.1186/ar3173subject
Has Abstractpub_date
2010-01-01 00:00:00pages
R201issue
5eissn
1478-6354issn
1478-6362pii
ar3173journal_volume
12pub_type
杂志文章abstract:BACKGROUND:Anti-citrullinated protein antibody (ACPA) reactivities precede clinical onset of rheumatoid arthritis (RA), and it has been suggested that ACPA reactivities towards distinct target proteins may be associated with differences in RA phenotypes. We aimed to assess the prevalence of baseline ACPA reactivities i...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-018-1635-7
更新日期:2018-07-13 00:00:00
abstract:INTRODUCTION:Bone marrow lesions (BMLs) play an important role in knee osteoarthritis, but their etiology is not well understood. The aim of this longitudinal study was to describe the association between dietary factors, serum lipids, and BMLs. METHODS:In total, 394 older men and women (mean age, 63 years; range, 52 ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3689
更新日期:2012-01-18 00:00:00
abstract:INTRODUCTION:The interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis. METHODS:Human CD14+ cells were isolated fro...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2936
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle. METHODS...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3540
更新日期:2011-01-01 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: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: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: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::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:INTRODUCTION:The c-Jun N-terminal kinase (JNK) is a key regulator of matrix metalloproteinase (MMP) and cytokine production in rheumatoid arthritis (RA) and JNK deficiency markedly protects mice in animal models of arthritis. Cytokine-induced JNK activation is strictly dependent on the mitogen-activated protein kinase ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3750
更新日期:2012-02-21 00:00:00
abstract::The development of spontaneous autoimmunity in inbred strains of rodents has allowed us to investigate the molecular basis of chronic inflammatory disease in ways that would not be possible in humans. Recently, two new mouse models of autoimmune inflammatory polyarthritis have been reported that demonstrate how altera...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1185
更新日期:2004-01-01 00:00:00
abstract:INTRODUCTION:Costochondral cells may be isolated with minimal donor site morbidity and are unaffected by pathologies of the diarthrodial joints. Identification of optimal exogenous stimuli will allow abundant and robust hyaline articular cartilage to be formed from this cell source. METHODS:In a three factor, two leve...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4409
更新日期:2013-01-01 00:00:00
abstract:INTRODUCTION:HLA-B*35 is associated with increased risk of developing pulmonary hypertension in SSc patients. We previously reported that HLA-B*35 induces endothelial cell dysfunction via activation of ER stress/UPR and upregulation of the inflammatory response. Because PBMCs from lcSSc-PAH patients are also characteri...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0881-1
更新日期:2015-12-16 00:00:00
abstract:BACKGROUND:Sarcopenic obesity, associated with greater risk of cardiovascular disease (CVD) and mortality in rheumatoid arthritis (RA), may be related to dysregulated muscle remodeling. To determine whether exercise training could improve remodeling, we measured changes in inter-relationships of plasma galectin-3, skel...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/s13075-018-1786-6
更新日期:2018-12-27 00:00:00
abstract:BACKGROUND:Lack of adequate self-care, frequent admissions, and poor quality of life are common and serious problems in adult patients with systemic lupus erythematosus (SLE). Some studies have revealed that transitional care is effective in improving self-care and quality of life as well as reducing rehospitalization ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-018-1670-4
更新日期:2018-08-16 00:00:00
abstract:BACKGROUND:Systemic sclerosis (SSc) is a rare disease with studies limited by small sample sizes. Electronic health records (EHRs) represent a powerful tool to study patients with rare diseases such as SSc, but validated methods are needed. We developed and validated EHR-based algorithms that incorporate billing codes ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2092-7
更新日期:2019-12-30 00:00:00
abstract::Neonatal lupus erythematosus is a rare disorder caused by the transplacental passage of maternal autoantibodies. The 52-kDa Ro/SSA antigen (Ro52) ribonucleoprotein represents an antigenic target strongly associated with the autoimmune response in mothers whose children have neonatal lupus and cardiac conduction distur...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1848
更新日期:2006-01-01 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:BACKGROUND:Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc), associated with a progressive elevation in pulmonary vascular resistance and subsequent right heart failure and death. Due to unspecific symptoms, the diagnosis of PAH is often delayed. On this basis, it is of great v...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02218-8
更新日期:2020-06-01 00:00:00
abstract::An impaired differentiation of naive CD4+ T cells towards Th2 cells may contribute to the chronic tissue-destructive T-cell activity in rheumatoid arthritis (RA). The differentiation of naive CD4+ T cells into memory Th2 cells by IL-7 in comparison with that by IL-4 was studied in RA patients and in healthy controls. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar790
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:Increased expression of toll-like receptor 4 (TLR4) and its endogenous ligands, is characteristic of rheumatoid arthritis (RA) synovitis. In this study, we evaluated how these TLR4 ligands may drive pathogenic processes and whether the fine profiling of anti-citrullinated protein antibodies (ACPA) based on t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1128-5
更新日期:2016-10-06 00:00:00
abstract:BACKGROUND:Social media may complement traditional data sources to answer comparative effectiveness/safety questions after medication licensure. METHODS:The Treato platform was used to analyze all publicly available social media data including Facebook, blogs, and discussion boards for posts mentioning inflammatory ar...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1251-y
更新日期:2017-03-07 00:00:00
abstract:INTRODUCTION:In this study, we aimed to determine the relationship between flow-mediated endothelium-dependent vasodilatation (FMD) and carotid artery intima-media wall thickness (IMT), two surrogate markers of atherosclerosis, in a series of Spanish patients with rheumatoid arthritis (RA) without clinically evident ca...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3382
更新日期:2011-06-22 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: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:INTRODUCTION:Osteoarthritis (OA) is a degenerative disease characterized by cartilage breakdown in the synovial joints. The presence of low-grade inflammation in OA joints is receiving increasing attention, with synovitis shown to be present even in the early stages of the disease. How the synovial inflammation arises ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3555
更新日期:2012-01-08 00:00:00
abstract:BACKGROUND:Clinical remission can be maintained after the discontinuation of biological disease-modifying antirheumatic drugs (bDMARDs) in some patients with rheumatoid arthritis (RA) (bDMARD-free remission (BFR)). It is unknown which bDMARD is advantageous for achieving BFR or under which conditions BFR can be conside...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-018-1673-1
更新日期:2018-08-03 00:00:00
abstract:INTRODUCTION:Osteoclastogenesis plays an important role in the bone erosion of rheumatoid arthritis (RA). Recently, Notch receptors have been implicated in the development of osteoclasts. However, the responsible Notch ligands have not been identified yet. This study was undertaken to determine the role of individual N...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3758
更新日期:2012-03-05 00:00:00
abstract:INTRODUCTION:We previously demonstrated that a single-chain fragment variable (scFv) specific to collagen type II (CII) posttranslationally modified by reactive oxygen species (ROS) can be used to target anti-inflammatory therapeutics specifically to inflamed arthritic joints. The objective of the present study was to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4613
更新日期:2014-07-16 00:00:00
abstract:BACKGROUND:In recent decades, low-level laser therapy (LLLT) has been widely used to relieve pain caused by different musculoskeletal disorders. Though widely used, its reported therapeutic outcomes are varied and conflicting. Results similarly conflict regarding its usage in patients with nonspecific chronic low back ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1186/s13075-015-0882-0
更新日期:2015-12-15 00:00:00