Abstract:
BACKGROUND:Nitric oxide and prostaglandin E2 (PGE2play pivotal roles in both the pathogenesis of osteoarthritis and catabolic processes in articular cartilage. These mediators are influenced by both IL-1beta and mechanical loading, and involve alterations in the inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX)-2 enzymes. To identify the specific interactions that are activated by both types of stimuli, we examined the effects of dynamic compression on levels of expression of iNOS and COX-2 and involvement of the p38 mitogen-activated protein kinase (MAPK) pathway. METHODS:Chondrocyte/agarose constructs were cultured under free-swelling conditions with or without IL-1beta and/or SB203580 (inhibitor of p38 MAPK) for up to 48 hours. Using a fully characterized bioreactor system, constructs were subjected to dynamic compression for 6, 12 and 48 hours under similar treatments. The activation or inhibition of p38 MAPK by IL-1beta and/or SB203580 was analyzed by western blotting. iNOS, COX-2, aggrecan and collagen type II signals were assessed utilizing real-time quantitative PCR coupled with molecular beacons. Release of nitrite and PGE2 was quantified using biochemical assays. Two-way analysis of variance and the post hoc Bonferroni-corrected t-test were used to examine data. RESULTS:IL-1beta activated the phosphorylation of p38 MAPK and this effect was abolished by SB203580. IL-1beta induced a transient increase in iNOS expression and stimulated the production of nitrite release. Stimulation by either dynamic compression or SB203580 in isolation reduced the IL-1beta induced iNOS expression and nitrite production. However, co-stimulation with both dynamic compression and SB203580 inhibited the expression levels of iNOS and production of nitrite induced by the cytokine. IL-1beta induced a transient increase in COX-2 expression and stimulated the cumulative production of PGE2 release. These effects were inhibited by dynamic compression or SB203580. Co-stimulation with both dynamic compression and SB203580 restored cytokine-induced inhibition of aggrecan expression. This is in contrast to collagen type II, in which we observed no response with the cytokine and/or SB203580. CONCLUSION:These data suggest that dynamic compression directly influences the expression levels of iNOS and COX-2. These molecules are current targets for pharmacological intervention, raising the possibility for integrated pharmacological and biophysical therapies for the treatment of cartilage joint disorders.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Chowdhury TT,Arghandawi S,Brand J,Akanji OO,Bader DL,Salter DM,Lee DAdoi
10.1186/ar2389subject
Has Abstractpub_date
2008-01-01 00:00:00pages
R35issue
2eissn
1478-6354issn
1478-6362pii
ar2389journal_volume
10pub_type
杂志文章abstract:INTRODUCTION:Pain remains the most important problem for people with rheumatoid arthritis (RA). Active inflammatory disease contributes to pain, but pain due to non-inflammatory mechanisms can confound the assessment of disease activity. We hypothesize that augmented pain processing, fibromyalgic features, poorer menta...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0525-5
更新日期:2015-01-20 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:Mutations in the NLRP3 gene are associated with the dominantly inherited cryopyrin-associated periodic syndrome (CAPS). The significance of the V198M variant is unclear; it has been reported in association with various CAPS phenotypes and as a variant of uncertain consequence. The aim of this study was to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4171
更新日期:2013-02-19 00:00:00
abstract:INTRODUCTION:The present study examined the effect of C-type natriuretic peptide (CNP) on the anabolic and catabolic activities in chondrocyte/agarose constructs subjected to dynamic compression. METHODS:Constructs were cultured under free-swelling conditions or subjected to dynamic compression with low (0.1 to 100 pM...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3459
更新日期:2011-01-01 00:00:00
abstract:INTRODUCTION:Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of a...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0814-z
更新日期:2015-10-22 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: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:BACKGROUND:Up to 12% of patients with systemic sclerosis (SSc) have anti-neutrophil cytoplasmic antibodies (ANCA). However, the majority of these patients do not manifest ANCA-associated vasculitis (AAV) and the significance of ANCA in these patients is unclear. The aim of this study is to determine the prevalence of A...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-019-1839-5
更新日期:2019-02-14 00:00:00
abstract:BACKGROUND:To investigate the association between knee pain and risk factors including low back pain and to develop a score to predict new knee pain in an older population, using population-based longitudinal cohort data. METHODS:We collected a questionnaire on self-reported knee pain and demographic data in a systema...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-1884-0
更新日期:2019-04-15 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::A dose-escalating phase II trial studied masitinib, an oral tyrosine kinase inhibitor, in 43 patients with rheumatoid arthritis. Masitinib induced American College of Rheumatology (ACR)20, ACR50 and ACR70 responses in 54%, 26% and 8% of patients, respectively. A placebo group was not included. Thirty-seven per cent of...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar2734
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:High levels of the oncoprotein survivin may be detected in the majority of patients with early rheumatoid arthritis (RA). Survivin is a sensitive predictor of joint damage and persistent disease activity. Survivin-positive patients are often poor responders to antirheumatic and biological treatment. The ai...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4438
更新日期:2014-01-16 00:00:00
abstract::Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from a loss of tolerance to multiple self antigens, and characterized by autoantibody production and inflammatory cell infiltration in target organs, such as the kidneys and brain. T cells are critical players in SLE pathophysiology as they regulate...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3251
更新日期:2011-03-17 00:00:00
abstract::The changes occurring in the field of rheumatoid arthritis (RA) over the past decade or two have encompassed new therapies and, in particular, a new look at the clinical characteristics of the disease in the context of therapeutic improvements. It has been shown that composite disease activity indices have special mer...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2535
更新日期:2009-01-01 00:00:00
abstract::In rheumatoid arthritis, T cells, B cells, macrophages, and dendritic cells invade the synovial membranes, establishing complex microstructures that promote inflammatory/tissue destructive lesions. B cell involvement has been considered to be limited to autoantibody production. However, recent studies suggest that B c...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1737
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are chronic immune-mediated disorders complicated by vascular organ damage. The aim of this study was to examine the serum levels of the markers of neoangiogenesis: endostatin and vascular endothelial growth factor (VEGF), in our unselecte...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0756-5
更新日期:2015-08-28 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:BACKGROUND:Restoring normal physical functioning is a major therapeutic aim in the management of rheumatoid arthritis (RA). It is unknown, whether the extent of synovial inflammation quantified by musculoskeletal ultrasound (US) can predict current or future capacity for physical functioning. To answer this question we...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1208-6
更新日期:2017-01-13 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:INTRODUCTION:Microcirculation dysfunction is a typical feature of systemic sclerosis (SSc) and represents the earliest abnormality of primary myocardial involvement. We assessed coronary microcirculation status by combining two functional tests in SSc patients and estimating its impact on disease outcome. METHODS:Fort...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4136
更新日期:2013-01-09 00:00:00
abstract:BACKGROUND:The aim of this study was to develop a patient-reported questionnaire that is suitable to detect periodontitis (PD) in patients with rheumatoid arthritis (RA). METHODS:A self-reported questionnaire containing 12 items potentially relevant to PD and dentists' semiquantitative assessment of PD (no/mild/modera...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-019-1982-z
更新日期:2019-08-29 00:00:00
abstract:BACKGROUND:Bone marrow mesenchymal stem cells (BM-MSCs) can dampen inflammation in animal models of inflammatory rheumatisms and human osteoarthritis. They are expected to be a solution for numerous human conditions. However, in rheumatoid arthritis (RA) and spondyloarthritis (SpA), subsets of subchondral BM-MSCs might...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13075-019-2014-8
更新日期:2019-11-13 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
abstract:INTRODUCTION:Serious infection, cardiovascular disease, and mortality are increased in rheumatoid arthritis (RA). Whether RA affects the risk for these complications after total joint arthroplasty (TJA) is unknown, we hypothesize that it does. We compared the occurrence of 30-day postoperative complications and mortali...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4385
更新日期:2013-01-01 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: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:Galactosylation of immunoglobulin G (IgG) is reduced in rheumatoid arthritis (RA) and assumed to correlate with inflammation and altered humoral immunity. IgG hypogalactosylation also increases with age. To investigate dependencies in more detail, we compared IgG hypogalactosylation between patients with RA,...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1540-0
更新日期:2018-03-14 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
abstract:INTRODUCTION:Mesenchymal stem cells (MSCs) represent promising applications in rheumatoid arthritis (RA). However, the inflammatory niche in the RA synovium could adversely affect MSC function. This study was designed to investigate biologic and immunologic properties of synovium-derived MSCs (SMSCs) in RA, with partic...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4355
更新日期:2013-10-29 00:00:00
abstract::The characteristic of a biomarker that makes it a useful surrogate is the ability to identify a high risk of clinically important benefits or harms occurring in the future. A number of definitions or descriptions of surrogate definition have been put forward. Most recently the Institute of Medicine of the National Aca...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4176
更新日期:2013-01-01 00:00:00