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 is unclear, but proteins in the synovial fluid of affected joints could conceivably contribute. We therefore surveyed the proteins present in OA synovial fluid and assessed their immunostimulatory properties. METHODS:We used mass spectrometry to survey the proteins present in the synovial fluid of patients with knee OA. We used a multiplex bead-based immunoassay to measure levels of inflammatory cytokines in serum and synovial fluid from patients with knee OA and from patients with rheumatoid arthritis (RA), as well as in sera from healthy individuals. Significant differences in cytokine levels between groups were determined by significance analysis of microarrays, and relations were determined by unsupervised hierarchic clustering. To assess the immunostimulatory properties of a subset of the identified proteins, we tested the proteins' ability to induce the production of inflammatory cytokines by macrophages. For proteins found to be stimulatory, the macrophage stimulation assays were repeated by using Toll-like receptor 4 (TLR4)-deficient macrophages. RESULTS:We identified 108 proteins in OA synovial fluid, including plasma proteins, serine protease inhibitors, proteins indicative of cartilage turnover, and proteins involved in inflammation and immunity. Multiplex cytokine analysis revealed that levels of several inflammatory cytokines were significantly higher in OA sera than in normal sera, and levels of inflammatory cytokines in synovial fluid and serum were, as expected, higher in RA samples than in OA samples. As much as 36% of the proteins identified in OA synovial fluid were plasma proteins. Testing a subset of these plasma proteins in macrophage stimulation assays, we found that Gc-globulin, α1-microglobulin, and α2-macroglobulin can signal via TLR4 to induce macrophage production of inflammatory cytokines implicated in OA. CONCLUSIONS:Our findings suggest that plasma proteins present in OA synovial fluid, whether through exudation from plasma or production by synovial tissues, could contribute to low-grade inflammation in OA by functioning as so-called damage-associated molecular patterns in the synovial joint.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Sohn DH,Sokolove J,Sharpe O,Erhart JC,Chandra PE,Lahey LJ,Lindstrom TM,Hwang I,Boyer KA,Andriacchi TP,Robinson WHdoi
10.1186/ar3555subject
Has Abstractpub_date
2012-01-08 00:00:00pages
R7issue
1eissn
1478-6354issn
1478-6362pii
ar3555journal_volume
14pub_type
杂志文章abstract:OBJECTIVE:To assess the associations between aspartate transaminase/alanine transaminase ratio (DRR) and mortality in patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD). PATIENTS AND METHODS:This was a retrospective cohort study, which included 522 patients with PM/DM-ILD whose...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02286-w
更新日期:2020-09-20 00:00:00
abstract::Susceptibility for giant cell arteritis increases with chronological age, in parallel with age-related restructuring of the immune system and age-induced remodeling of the vascular wall. Immunosenescence results in shrinkage of the naïve T-cell pool, contraction of T-cell diversity, and impairment of innate immunity. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3358
更新日期:2011-08-02 00:00:00
abstract:INTRODUCTION:CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor that is activated in the synovium in rheumatoid arthritis (RA) and promotes expression of various matrix metalloproteinases. In this study, we examined whether C/EBPβ mediates the expression of receptor activator of nuclear factor-kappa-B ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0532-6
更新日期:2015-02-17 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::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::Bone morphogenetic proteins (BMPs) are expressed during osteogenesis and their action is regulated by corresponding BMP inhibitors. Chordin (a well recognized BMP inhibitor) and BMP-2 are expressed during osteogenic differentiation of human mesenchymal stem cells. Chordin inhibition induces human mesenchymal stem cell...
journal_title:Arthritis research & therapy
pub_type: 社论
doi:10.1186/ar2467
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:Dual-energy computed tomography (DECT) has potential for monitoring urate deposition in patients with gout. The aim of this prospective longitudinal study was to analyse measurement error of DECT urate volume measurement in clinically stable patients with tophaceous gout. METHODS:Seventy-three patients wi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4343
更新日期:2013-10-23 00:00:00
abstract:INTRODUCTION:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Cardiovascular disease (CVD) is common and a major cause of mortality. Studies on cardiovascular morbidity are abundant, whereas mortality studies focusing on cardiovascular outcomes are scarce. The aim of this study was to investigate cau...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3759
更新日期:2012-01-01 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
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更新日期:2018-08-16 00:00:00
abstract:BACKGROUND:In previous studies, we demonstrated that the NEMO score, i.e. the cumulative number of microhaemorrhages (MHEs) and microthromboses (MTs), observed in nailfold videocapillaroscopy was a good indicator of the steady state level of disease activity (DA) in patients with systemic sclerosis (SSc) when the Europ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2032-6
更新日期:2019-11-29 00:00:00
abstract::Magnetic resonance imaging bone marrow edema is an imaging feature that has been described in many conditions, including osteomyelitis, overuse syndromes, avascular necrosis, trauma, and inflammatory arthritides. In rheumatoid arthritis (RA), bone edema has special significance as it has been shown to be a common and ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4035
更新日期:2012-09-28 00:00:00
abstract:INTRODUCTION:Interleukin-1 (IL-1) blockade is the treatment of choice of cryopyrin associated periodic syndromes (CAPS). Anti-IL-1 monoclonal antibody (canakinumab) was recently registered. However no clear data are available on the optimal schedule of administration of this drug. The aim of the present study was to an...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/ar4184
更新日期:2013-02-26 00:00:00
abstract:BACKGROUND:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of autoantibodies to multiple self-antigens, including heat shock proteins (HSP). Because of the increased expression of HSP90 and abnormal immune responses to it in SLE, we investigated whether an HSP90 DNA vacc...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02246-4
更新日期:2020-06-22 00:00:00
abstract:INTRODUCTION:Semaphorin 3A (sema3A) and neuropilin-1 (NP-1) play a regulatory role in immune responses and have a demonstrated effect on the course of collagen induced arthritis. This study was undertaken to evaluate the role of sema3A and NP-1 in the pathogenesis of systemic lupus erythematosus (SLE) and the specific ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3881
更新日期:2012-06-14 00:00:00
abstract:INTRODUCTION:Bone morphogenetic proteins (BMPs) are critical growth factors in the osteogenic differentiation of progenitor cells during development in embryos and fracture repair in adults. Although recombinant BMPs are in use clinically, their clinical efficiency needs to be improved. The biological activities of BMP...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2436
更新日期:2008-01-01 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:INTRODUCTION:Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and organs. Increase in oxidative stress and platelet-derived growth factor receptor (PDGFR) activation promote collagen I (Col I) production, leading to fibrosis in SSc. Lipoic acid (LA) and its active metabolite...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-014-0411-6
更新日期:2014-01-01 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: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:Intraarticular administration of autologous conditioned serum (ACS) recently demonstrated some clinical effectiveness in treatment of osteoarthritis (OA). The current study aims to evaluate the in vitro effects of ACS on cartilage proteoglycan (PG) metabolism, its composition and the effects on synovial fl...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3050
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Established rheumatoid arthritis (RA) patients display differentially expressed genes coding for cytokine/chemokine-mediated immunity compared to healthy controls. It is unclear, however, if in the pre-arthritis phase of clinically suspect arthralgia (CSA) expression of immune genes differ between patients w...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02361-2
更新日期:2020-11-09 00:00:00
abstract::Hypoxia, which leads to dysfunctional cell metabolism, and complement activation both play central roles in the pathogenesis of rheumatoid arthritis (RA). Recent studies have reported that mice deficient for the complement-inhibitory protein CD59 show enhanced susceptibility to antigen-induced arthritis and reported t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2019
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:A number of occupational risk factors are discussed in relation to the development and progress of knee joint diseases (for example, working in a kneeling or squatting posture, lifting and carrying heavy weights). Besides the occupational factors, a number of individual risk factors are important. The dist...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3015
更新日期:2010-01-01 00:00:00
abstract::Abnormalities in lymphocyte signaling cascades are thought to play an important role in the development of autoimmune disease. However, the large amount of cellular material needed for standard biochemical assessment of signaling status has made it difficult to evaluate putative abnormalities completely using primary ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1155
更新日期:2004-01-01 00:00:00
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 algin...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4415
更新日期:2013-01-01 00:00:00
abstract:INTRODUCTION:Since current treatment options for patients suffering from active rheumatoid arthritis (RA) remain inadequate, especially for those unresponsive to disease-modifying antirheumatic drugs (DMARDs), new and improved medication is needed. This study evaluates the safety and efficacy of masitinib (AB1010), a p...
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/ar2740
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:The in vitro pharmacology of baricitinib, upadacitinib, and tofacitinib was evaluated to understand differences among these JAK inhibitors (JAKis) at the cellular level. METHODS:Peripheral blood mononuclear cells from healthy donors were incubated with different JAKis, levels of phosphorylated signal transd...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-1964-1
更新日期:2019-08-02 00:00:00
abstract:INTRODUCTION:Vagus nerve stimulation (VNS) exerts beneficial anti-inflammatory effects in various animal models of inflammation, including collagen-induced arthritis, and is implicated in representing a novel therapy for rheumatoid arthritis. However, evidence of anti-inflammatory effects of VNS in humans is very scarc...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-015-0667-5
更新日期:2015-06-07 00:00:00
abstract:INTRODUCTION:In this study, we sought to address changes in blood lymphocyte subpopulations and labial salivary gland (LSG) inflammation after belimumab treatment in patients with primary Sjögren's syndrome (pSS) and to identify predictors of response to treatment. METHODS:Sequential blood lymphocyte subsets and LSG b...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0750-y
更新日期:2015-09-04 00:00:00
abstract::Antibodies to double-stranded DNA are important in the pathogenesis of nephritis, a major clinical manifestation in lupus patients. Since earlier diagnosis of renal involvement may lead to better outcomes, identification of the nephritogenic specificity of lupus-associated autoantibodies is important in understanding ...
journal_title:Arthritis research & therapy
pub_type: 社论
doi:10.1186/ar2869
更新日期:2009-01-01 00:00:00