Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advanced glycation end-product (AGE) pentosidine has previously been demonstrated in different tissues and body fluids. It was suggested as a novel marker for evaluating the pathologic activity in rheumatoid arthritis (RA). In this study we analyzed the relation between pentosidine and markers of inflammation, cartilage turnover, immune response, and disease status of RA. Using HPLC, we analyzed pentosidine in serum and synovial fluid from 39 patients with RA and in serum from 38 healthy controls. Cartilage oligomeric matrix protein (COMP) and antibodies to CCP (anti-CCP) were measured by ELISA. Clinical disease status was assessed by Disease Activity Score 28 (DAS 28) and functional status by Health Assessment Questionnaire (HAQ). We demonstrated significantly higher serum levels of pentosidine in RA patients in comparison with controls. Pentosidine in serum significantly correlated with pentosidine in synovial fluid. Serum pentosidine levels were associated with erythrocyte sedimentation rate (p<0.03) but not with CRP, COMP, anti-CCP antibodies, DAS 28, or HAQ. In contrast to previous studies, we could not show any correlation of pentosidine levels with inflammatory status, clinical disease activity, markers of immune response, or cartilage breakdown. However, AGEs can be suggested as important players participating in joint destruction rather than markers of disease activity.
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PMID:Advanced glycation end-product pentosidine is not a relevant marker of disease activity in patients with rheumatoid arthritis. 1729 11

Elevated levels of the pro-inflammatory cytokine, interleukin-18 (IL-18) have recently been demonstrated in osteoarthritic cartilage. However, the effects of IL-18 on chondrocyte signalling and matrix biosynthesis are poorly understood. Therefore, the present study was undertaken to further characterize the impact of IL-18 on human articular chondrocyte in vitro. Human articular chondrocytes were stimulated with various concentrations of recombinant human IL-18 (1, 10, 100 ng/ml) for 0, 4, 8, 12, 24, 48, 72 h in vitro. The effects of IL-18 on the cartilage-specific matrix protein collagen type II, the cytoskeletal protein vinculin, the cell matrix signal transduction receptor beta-integrin, key signalling proteins of the MAPKinase pathway (such as SHC (Sarc Homology Collagen) and activated MAPKinase [ERK-1/-2]), the pro-inflammatory enzyme cyclo-oxygenase-2 (COX-2) and the apoptosis marker activated caspase-3 were evaluated by Western blot analysis and immunofluorescence labelling. Morphological features of IL-18 stimulated chondrocytes were estimated by transmission electron microscopy. IL-18 lead to inhibition of collagen type II-deposition, decreased beta-integrin receptor and vinculin synthesis, SHC and MAPKinase activation, increased COX-2 synthesis and activation of caspase-3 in chondrocytes in a time- and dose-dependent manner. Furthermore, chondrocytes treated with IL-18 exhibited typical morphological features of apoptosis as revealed by transmission electron microscopy. Taken together, the results of the present study underline key catabolic events mediated by IL-18 signalling in chondrocytes such as loss of cartilage-specific matrix and apoptosis. Inhibition of MAPKinase signalling is hypothesized to contribute to these features. Future therapeutics targeting IL-18 signalling pathways may be beneficial in rheumatoid arthritis and osteoarthritis therapy.
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PMID:Interleukin-18 induces apoptosis in human articular chondrocytes. 1733 Aug 2

Recently, it has become possible to measure the concentration of serum cartilage oligomeric matrix protein (COMP) in various arthritis, and it is expected to be a novel biomarker indicative of cartilage destruction. In this study, we evaluated the diagnostic effectiveness of serum COMP in rheumatic diseases and analyzed the inhibition of cartilage destruction in patients with rheumatoid arthritis who were prescribed with infliximab (IFX) for one year. The changes in the concentration of serum COMP and the joint narrow space of Sharp score (Delta Sharp-JNS) were evaluated. The level of serum COMP decreased from 23.04+/-7.14 U/l to 8.69+/-2.89 U/l (p<0.005) and improved Delta Sharp-JNS (-0.50+/-6.38 points). We believed that these results were influenced by the effects of methotrexate (MTX) that was prescribed together with IFX, and we analyzed the group that was administered only MTX therapy as a reference. However, the serum COMP concentration and Sharp-JNS in the MTX group did not decrease. The serological and radiological results revealed that IFX inhibited cartilage destruction, and it is possible that serum COMP is one of the novel biomarkers in RA patients treated with anti-tumor necrosis factor-alpha antibody therapy.
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PMID:[Evidence of cartilaginous benefit of treatment with infliximab in rheumatoid arthritis using measurement of serum COMP]. 1733 4

Rheumatoid arthritis may take an unfavourable course leading to rapid functional decline in a certain percentage of patients. Early identification of these patients is desirable. The aim of this study was to evaluate clinical and laboratory parameters for their value in the prediction of bad outcome. A total of 172 patients with early arthritis were followed for 3 years. Higher initial values for erythrocyte sedimentation rate, IgG and IgM rheumatoid factor, serum concentration of cartilage oligomeric matrix protein, Health Assessment Questionnaire score, Larsen score of feet, disease activity score, and swollen and tender joint count predicted worse outcome. An association with the presence of IgA rheumatoid factor or anti-cyclic-citrullinated peptide could not be established. We conclude that prognosis in an individual with rheumatoid arthritis depends on many factors. The determination of independent prognostic factors for progression of rheumatoid arthritis is a valuable tool in early arthritis to select patients for more aggressive therapy.
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PMID:Predicting factors for severity of rheumatoid arthritis: a prospective multicenter cohort study of 172 patients over 3 years. 1742 38

Recent studies have shown a strong correlation between the nervous, endocrine and immune systems. Knowledge of how these systems interact is important for understanding the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and to open new therapeutic perspectives. New theories suggest that in RA there is an inappropriate response of the hypothalamic-pituitary-adrenal axis to the increase in pro-inflammatory cytokines, resulting in a corticosteroid (CS) insufficiency state. While recent observations have questioned the positive effect of CS on the progression of joint damage, efficacious new drugs such as anti-TNF have attracted attention to agents without the side effects of CS. Cartilage oligomeric matrix protein, a new biohumoral marker, has recently led to a re-evaluation of CS in RA therapy.
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PMID:Corticosteroids, a review. 1746 31

The triangular fibrocartilage complex (TFCC) transmits load from the wrist to the ulna and stabilizes the distal radioulnar joint. Damage to it is a major cause of wrist pain. Although its basic structure is well established, little is known of its molecular composition. We have analysed the immunohistochemical labelling pattern of the extracellular matrix of the articular disc and the meniscal homologue of the TFCC in nine elderly individuals (age range 69-96 years), using a panel of monoclonal antibodies directed against collagens, glycosaminoglycans, proteoglycans and cartilage oligomeric matrix protein (COMP). Although many of the molecules (types I, III and VI collagen, chondroitin 4 sulphate, dermatan sulphate and keratan sulphate, the oversulphated epitope of chondroitin 6 sulphate, versican and COMP) were found in all parts of the TFCC, aggrecan, link protein and type II collagen were restricted to the articular disc and to entheses. They were thus not a feature of the meniscal homologue. The shift in tissue phenotype within the TFCC, from a fibrocartilaginous articular disc to a more fibrous meniscal homologue, correlates with biomechanical data suggesting that the radial region is stiff and subject to considerable stress concentration. The presence of aggrecan, link protein and type II collagen in the articular disc could explain why the TFCC is destroyed in rheumatoid arthritis, given that it has been suggested that autoimmunity to these antigens results in the destruction of articular cartilage. The differential distribution of aggrecan within the TFCC is likely to be reflected by regional differences in water content and mobility on the radial and ulnar side. This needs to be taken into account in the design of improved MRI protocols for visualizing this ulnocarpal complex of the wrist.
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PMID:An immunohistochemical study of the triangular fibrocartilage complex of the wrist: regional variations in cartilage phenotype. 1753 98

Spleen tyrosine kinase (Syk), a key mediator of immunoreceptor signaling in inflammatory cells, is essential for immune complex-mediated signal transduction initiated by activated receptors for immunoglobulin G. In collagen-induced arthritis, R788/R406, a novel and potent small molecule Syk inhibitor suppressed clinical arthritis, bone erosions, pannus formation, and synovitis. Serum anti-collagen type II antibody levels were unaltered, while the half-life of exogenous antibody was extended when co-administered with R406. Expression of the targeted kinase (Syk) in synovial tissue correlated with the joint level of inflammatory cell infiltrates and was virtually undetectable in treated rats. Syk inhibition suppressed synovial cytokines and cartilage oligomeric matrix protein (COMP) in serum, suggesting a sensitive and reliable biomarker for R406 activity. These results highlight the role of activating Fcgamma receptors in inflammatory synovitis and suggest that interruption of the signaling cascade with a novel Syk inhibitor may be a useful addition to immunosuppressive disease-modifying anti-rheumatic drugs currently used in the treatment of human autoimmune diseases such as rheumatoid arthritis.
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PMID:Inflammation and bone erosion are suppressed in models of rheumatoid arthritis following treatment with a novel Syk inhibitor. 1766 59

Cartilage oligomeric matrix protein (COMP) is a tissue-specific noncollagenous protein that was first detected in the serum and the synovial fluid of patients suffering from rheumatic disorders, such as rheumatoid arthritis, reactive arthritis, juvenile chronic arthritis, and osteoarthritis. In this review, the authors consider serum COMP levels in different diseases and discuss their study of patients with rheumatoid arthritis treated with anti-TNF-alpha, to evaluate whether COMP is able to predict a rapid and sustained clinical response to these drugs. They observe that patients with high COMP levels have a lower ACR 70 response independently of the state of systemic inflammation, and conclude that COMP seems to have a pathogenetic role that is independent of the mechanisms regulating inflammatory processes.
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PMID:Cartilage oligomeric matrix protein level in rheumatic diseases: potential use as a marker for measuring articular cartilage damage and/or the therapeutic efficacy of treatments. 1789 3

The purpose of this article is to present the current state of knowledge regarding the structure and functions of articular cartilage. Articular cartilage is constructed with hyaline cartilage tissue. It is composed of chondrocytes located in lacunae and the extracellular matrix. The chondrial matrix contains water, collagen, proteglycans, non-collagenous matrix proteins, and lipids. Articular cartilage is devided into four zones - superficial, intermediate, deep, and calcified - on the basic of morphology, the orientation of collagen fiber, and the proteoglycan content. The dominant collagen of this tissue is Type II collagen, which, together with smaller quantities of other collagens (i.e. Types IX and XII), forms a network of fibers, with large, aggregating proteoglycans and smaller, non-aggregating proteoglycans. Proteoglycans are proteins that contain covalently attached glycosaminoglycans (GAGs), with water between them. The large aggregating proteoglycans, called "aggrecans", form aggregates that bind hyaluronic acid, and together with collagen they are responsible for the mechanical properties of cartilage. The smallnonaggregating proteoglycans, decorin and fibromodulin, limit the formation of collagen fibres. Other proteins in the cartilage matrix - chondrocalcin and the N-propetide of Type II collagen - participate in fiber formation. Yet other proteins - chondronectin, fibronectin, vitronectin and thrombospondin - take part in the interaction between the chondrocytes and the matrix. Cartilage oligomeric matrix protein (COMP) prevents the vascularization of the cartilage and, perhaps, is responsible for the repair process. The proteins known as Cart-1 and CEP-68 participate in chondrogenesis, while tenascin and Mgp are considered to be cartilage calcification inhibitors. Apart from the structural elements, chondrocytes produce substances that fulfill purely physiological functions: enzymes and cytokines. The enzymes - which include metalloproteinases, adamalysins, serine and cysteine proteases and their inhibitors - participate in cartilage matrix reconstruction. The cytokines - IL-1, TNF-alfa, IL-6, IL-8, and LIF - stimulate the chondrocytes to produce an increased amount of enzymes, while IL-4 inhibits this process. Human articular chondrocytes exibit the constitutive expression of class I molecules of the major histocompatibility complex (MHC), molecules regulating the activation of the complement, and after activation (e.g. under the influence of IFN-alfa, IL-1, TNF-a or in the course of arthritis), also MHC class II and ICAM-1 intracellular adhesion molecules. Numerous studies have shown that chondrocytes also have tissue-specific antigens, which induce the production of antibodies in patients with cartilage grafts, as well as those with rheumatoid arthritis and osteoarthritis. Some of these antibodies react with type II collagen, others are directed against other proteins i.e. anchorin CII and CH65. the role of these diverse molecules, which are present in cartilage cells and separated from the immune system by the matrix, remains unclear.
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PMID:The morphology and selected biological properties of articular cartilage. 1798 77

Cartilage oligomeric matrix protein is a non-collagenous extracellular matrix protein expressed primarily in cartilage, ligament, and tendon. Cartilage oligomeric matrix protein has been studied extensively because mutations in the gene cause two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia. Pseudoachondroplasia is a disproportionate dwarfing condition associated with joint abnormalities, while multiple epiphyseal dysplasia is less severe. Both of these skeletal dysplasias have a characteristic chondrocyte pathology that consists of intracellular retention of cartilage oligomeric matrix protein and other extracellular matrix proteins in an enlarged rough endoplasmic reticulum. This toxic intracellular retention of extracellular matrix proteins causes chondrocyte cell death thereby decreasing linear bone growth. Additionally, when cartilage oligomeric matrix protein and the other co-retained proteins are not exported to the extracellular matrix, the resulting matrix is abnormal and easily erodes with normal physical activity. Cartilage oligomeric matrix protein is also a marker for joint destruction associated osteoarthritis, rheumatoid arthritis, joint trauma, and intense activity. Serum cartilage oligomeric matrix protein levels are higher in aggressive cases of arthritis and levels are used to predict future disease progression. Recent studies have identified molecular functions of cartilage oligomeric matrix protein that may contribute to its role in skeletal disease. These molecular functions include: binding other ECM proteins, catalyzing polymerization of type II collagen fibrils, and regulation of chondrocyte proliferation. Here, we review cartilage oligomeric matrix protein's role in skeletal disease and potential molecular mechanisms.
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PMID:The role of cartilage oligomeric matrix protein (COMP) in skeletal disease. 1885 21


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