Abstract:
INTRODUCTION:Excess C/EBP homologous protein (CHOP) expression is one feature of the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress. Here, we focused on CHOP expression and function in chondrocytes. METHODS:We studied human knee osteoarthritis (OA) cartilage, bovine chondrocytes cultured in alginate and subjected to sub-lethal biomechanical injury, and knee chondrocytes of human autopsy donors. We performed siRNA knockdown and transfection. RESULTS:UPR activation was increased in human knee OA cartilage in situ, and in biomechanically injured cultured chondrocytes in vitro. In normal human chondrocytes, CHOP “gain of function” sensitized chondrocytes to IL-1β induced nitric oxide (NO) and matrix metalloproteinase (MMP)-3 release without inducing these responses by itself. Excess CHOP expression, by itself, induced superoxide production and apoptosis. Conversely, siRNA knockdown of CHOP and the UPR-specific mediator X-box binding protein (XBP1) inhibited NO release by >80% (P <0.0005) in response to IL-1β, and blunted MMP-3 release, whereas there were only minimal effects of the UPR mediator GRP78 on these responses. The anti-inflammatory metabolic “super-regulator” AMP kinase (AMPK) is known to limit UPR activation in vascular muscle cells. Here, CHOP supported the capacity of IL-1β to suppress AMPK activity in chondrocytes. We also observed that inhibition of AMPK activity promoted an increase in chondrocyte CHOP expression. Conversely, pharmacologic activation of AMPK by 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) blunted chondrocyte CHOP expression in response to biomechanical injury. CONCLUSIONS:Biomechanical injury and IL-1 signaling stimulate UPR activation in chondrocytes. CHOP mediates chondrocyte catabolic and apoptotic responses to IL-1β, and does so partly by inhibiting AMPK activity. Conversely, development of excess CHOP activity is limited by AMPK activity in chondrocytes. Our findings suggest a mechanism for potential chondroprotection by AICAR and other AMPK activators. The work is of translational relevance for OA, since several drugs that activate AMPK are already in the clinic for arthritis (for example, allosteric AMPK activators sodium salicylate and high dose aspirin, and methotrexate, which activates AMPK by generating AICAR).
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Husa M,Petursson F,Lotz M,Terkeltaub R,Liu-Bryan Rdoi
10.1186/ar4415subject
Has Abstractpub_date
2013-01-01 00:00:00pages
R218issue
6eissn
1478-6354issn
1478-6362pii
ar4415journal_volume
15pub_type
杂志文章abstract:BACKGROUND:This study aimed at investigating the effect of a resistance exercise intervention on the interstitial muscle levels of pro-inflammatory cytokines in fibromyalgia (FMS) and healthy controls (CON). METHODS:Twenty-four female patients with FMS (54 ± 8 years) and 27 female CON (54 ± 9 years) were subjected to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/s13075-016-1041-y
更新日期:2016-06-13 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:INTRODUCTION:UK guidelines recommend that all early active rheumatoid arthritis (RA) patients are offered combination disease-modifying antirheumatic drugs (DMARDs) and short-term corticosteroids. Anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA may differ in their treatment responses. We used d...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/ar4439
更新日期:2014-01-16 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:Inflammatory arthritis is associated with increased bone resorption and suppressed bone formation. The Wnt antagonist dickkopf-1 (DKK1) is secreted by synovial fibroblasts in response to inflammation and this protein has been proposed to be a master regulator of bone remodelling in inflammatory arthritis. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4065
更新日期:2012-10-18 00:00:00
abstract:INTRODUCTION:Despite recent advances in anti-inflammatory therapy, rheumatoid arthritis (RA) patients continue to rate pain as a priority. The etiology of RA pain is likely multifactorial, including both inflammatory and non-inflammatory components. In this study, we examine the association between disease activity, sl...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2842
更新日期:2009-01-01 00:00:00
abstract::Human T cell leukaemia virus type I (HTLV-I) is known to be involved in late-onset chronic polyarthritis as HTLV-I-associated arthropathy. However, it is unclear whether HTLV-I infection could modify the pathophysiology of osteoarthritis (OA). In this study we compared several inflammatory cytokines, such as C-termina...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1193
更新日期:2004-01-01 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::Irreversible destruction of joint structures is a major feature of osteoarthritis and rheumatoid arthritis. Fibrillar collagens in bone, cartilage and other soft tissues are critical for optimal joint form and function. Several approaches can be used to ascertain the role of collagenases, matrix metalloproteinases, in...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar600
更新日期:2003-01-01 00:00:00
abstract:INTRODUCTION:Pateclizumab (MLTA3698A) is a humanized mAb against lymphotoxin α (LTα), a transiently expressed cytokine on activated B and T cells (Th1, Th17), which are implicated in rheumatoid arthritis (RA) pathogenesis. This study was conducted to assess the safety, tolerability, < NOTE: For clarity and per AMA/S-W ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/ar3554
更新日期:2012-01-08 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:INTRODUCTION:miR-146a is one of the first identified miRNAs expressed differentially in osteoarthritis (OA) cartilage. However, the role it plays in OA pathogenesis is not clear. The aim of this study is to identify a molecular target of miR-146a, thereby elucidating its function in chondrocytes during OA pathogenesis....
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3798
更新日期:2012-04-16 00:00:00
abstract::Autoantibodies to the polymyositis/scleroderma (PM/Scl) complex have been associated with systemic sclerosis and PM/Scl overlap syndrome. The report of Hanke and colleagues in a recent issue of Arthritis Research and Therapy is the first to describe the separate evaluation of anti-PM/Scl-75c and PM/Scl-100 autoantibod...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar2646
更新日期:2009-01-01 00:00:00
abstract::The aim of this study was to evaluate the efficacy and safety of mycophenolate sodium (MPS) in patients with primary Sjögren syndrome (pSS) refractory to other immunosuppressive agents. Eleven patients with pSS were treated with MPS up to 1,440 mg daily for an observation period of 6 months in this single-center, open...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/ar2322
更新日期:2007-01-01 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::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:INTRODUCTION:Cartilage oligomeric matrix protein (COMP) is found at elevated concentrations in sera of patients with joint diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). We recently showed that COMP activates complement via the alternative pathway and that COMP-C3b complexes are present in sera of ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3694
更新日期:2012-01-20 00:00:00
abstract:INTRODUCTION:Sulfur compounds isolated from garlic exert anti-inflammatory properties. We recently isolated thiacremonone, a novel sulfur compound from garlic. Here, we investigated the anti-inflammatory and arthritis properties of thiacremonone through inhibition of NF-kappaB since NF-kappaB is known to be a target mo...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2819
更新日期:2009-01-01 00:00:00
abstract::Autoantibodies targeting intracellular proteins involved in key processes are detected in patients with idiopathic inflammatory myopathies. These myositis-specific autoantibodies have been increasingly demonstrated to correlate with distinct clinical phenotypes within the myositis spectrum. This review highlights the ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3275
更新日期:2011-03-18 00:00:00
abstract:INTRODUCTION:Standard measurements used to assess murine models of rheumatoid arthritis, notably paw thickness and clinical score, do not align well with certain aspects of disease severity as assessed by histopathology. We tested the hypothesis that non-invasive optical tomographic imaging of molecular biomarkers of i...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3038
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Ankylosing spondylitis (AS) shares many characteristics with inflammatory bowel disease (IBD). Intestinal microbiota most likely plays an important role in the development of IBDs and may also be involved in the pathogenesis of AS. We aimed to define and compare the fecal microbiota composition in patients w...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2018-4
更新日期:2019-11-27 00:00:00
abstract:BACKGROUND:Identification of risk factors for rapid joint destruction in early rheumatoid arthritis (RA) can be helpful for optimizing treatment, and improving our understanding of destructive arthritis and its mechanisms. The objective of this study was to investigate the relationship between early RA patient characte...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1575-2
更新日期:2018-05-02 00:00:00
abstract:INTRODUCTION:The aim of the study was to determine whether Olf1/EBF associated zinc finger protein (OAZ), a transcription factor encoded by a positional systemic lupus erythematosus (SLE) candidate gene, plays a functional role in the pathogenesis in SLE. METHODS:Gene expression levels in peripheral blood cells (PBLs)...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2972
更新日期:2010-01-01 00:00:00
abstract::Pulmonary involvement is a common complication of vasculitides, especially small vessel vasculitides. This review provides an overview of vasculitic manifestations of the lung as well as of other organs involved in vasculitides. Furthermore, it provides the diagnostic procedures required to asses a patient with vascul...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3307
更新日期:2011-06-30 00:00:00
abstract:INTRODUCTION:Extracellular matrix (ECM) degradation leads to malfunction of the cartilage in osteoarthritis (OA). Inflammatory cytokine interleukin-1 beta (IL-1β) functions in ECM degradation and prevents ECM synthesis by down-regulating the key transcription factor, Sox9, and consequently inhibiting ECM gene expressio...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4114
更新日期:2012-12-10 00:00:00
abstract:INTRODUCTION:To date, no single most-appropriate factor or delivery method has been identified for the purpose of mesenchymal stem cell (MSC)-based treatment of cartilage injury. Therefore, in this study we tested whether gene delivery of the growth factor Indian hedgehog (IHH) was able to induce chondrogenesis in huma...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3921
更新日期:2012-07-20 00:00:00
abstract::TNF inhibitors are currently considered both effective and cost-effective in patients with active rheumatoid arthritis (RA), particularly in patients who have not responded fully to methotrexate. There is substantial doubt about the cost-effectiveness of TNF inhibitors as initial treatment for active RA. New data from...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar2970
更新日期:2010-01-01 00:00:00
abstract::Collagen-induced arthritis (CIA) is a chronic inflammatory disease bearing all the hallmarks of rheumatoid arthritis, e.g. polyarthritis, synovitis, and subsequent cartilage/bone erosions. One feature of the disease contributing to joint damage is synovial hyperplasia. The factors responsible for the hyperplasia are u...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1205
更新日期:2004-01-01 00:00:00
abstract:INTRODUCTION:The aims of this study were to evaluate the diagnostic accuracy of blood B-cell subset profiling and immune-system activation marker assays in primary Sjögren's syndrome (pSS) and to assess whether adding these tools to the current laboratory item would improve the American-European Consensus Group (AECG) ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4442
更新日期:2014-01-17 00:00:00
abstract:INTRODUCTION:Monocytic cells play a central role in the aetiology of rheumatoid arthritis, and manipulation of the activation of these cells is an approach currently under investigation to discover new therapies for this and associated diseases. CD148 is a transmembrane tyrosine phosphatase that is highly expressed in ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4288
更新日期:2013-01-01 00:00:00