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)

This study details the macromolecular changes in cartilage involving proteoglycan molecules in an animal model of rheumatoid arthritis. In experimental chronic immune synovitis, fluorescein-conjugated mouse IgG and three monoclonal antibodies (MAbs 2G2, 2E9, and 6C9) portraying differing fine antigenic specificity for rabbit cartilage proteoglycan monomer were utilized to detail alterations in cartilage proteoglycan. In normal and IgG-immune animals, fluorescein isothiocynate (FITC)-conjugated MAbs 2G2 and 2E9 stained cellular/pericellular (C/PC) region intensely. FITC-MAb 2G2 stained cartilage interterritorial matrix as well. FITC-MAb 6C9 stained only C/PC area lightly but did not stain matrix. A marked decrease in staining intensity with FITC-MAb 2G2 was noted in cartilage sections derived from animals with immune synovitis. A corresponding increase in staining of cartilage was noted with FITC-MAb 6C9. The augmented staining of articular cartilage with FITC-MAb 6C9 was most prominent in femoral condyle tissue sections, which corresponded to the cartilaginous area, with the greatest severity in gross pathology. There was a slight augmentation of staining with FITC-MAb 2E9, especially in the C/PC area of medial/femoral cartilage. In addition, the animals with immune synovitis showed abortive cartilage repair exemplified by the presence of chondrocyte cloning (up to 20 cells) which correlated with increased FITC-MAb 2G2 staining. The differential MAb staining patterns of cartilaginous tissues obtained utilizing FITC-conjugated monoclonal antibodies with known fine antigenic specificity indicates a modulation of proteoglycans involving predominantly core protein epitopes in the articular cartilage of animals with chronic immune synovitis.
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PMID:Analysis of experimental immune synovitis cartilage using monoclonal antibodies reactive to rabbit proteoglycan. 335 87

Freshly isolated synovial fluid (SF) and plasma samples from 20 patients with rheumatoid arthritis (RA) and 9 patients with joint effusions of other diagnoses (non-RA) were immediately (without fractionation or dilution) used as a culture medium for murine articular cartilage. Both intact SF, and cell depleted SF were tested for the effect on proteoglycan synthesis (35S-incorporation) compared to the patients' plasma or standard tissue culture medium. In addition, the effect on proteoglycan degradation was measured using 35S-prelabeled cartilage. Intact SF and cell depleted SF were found to suppress chondrocyte metabolism both in the RA and non-RA group. In the group with RA a strong correlation was found between the number of cells in SF and the degree of suppression. In the same group, intact SF caused a markedly higher suppression of chondrocyte biosynthesis than in the non-RA group (p less than 0.02). In general, the suppressive effect of SF appeared to be at least partially related to inflammatory activity (number of cells in SF) rather than a specific feature of RA. During the short term exposure, no measurable breakdown of matrix proteoglycan was found, both in complete SF and cell depleted SF. Mechanistic studies suggest that neither hydrogen peroxide generated by polymorphonuclear neutrophil leukocytes nor variations in SF viscosity were responsible for the observed effects.
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PMID:Effects of synovial fluid and synovial fluid cells on chondrocyte metabolism in short term tissue culture. 336 31

Cartilage degradation is a characteristic feature of various types of human arthritis, notably rheumatoid arthritis and osteoarthritis. The influence of glucocorticoid and other steroid hormones on cartilage proteoglycan breakdown was examined in a model system in which breakdown is readily quantified by the release of proteoglycan from cultured bovine nasal cartilage discs. Endotoxin (bacterial lipopolysaccharides) treatment enhanced the depletion of cartilage proteoglycan by 2-3 fold. This was inhibited in a concentration-dependent manner by hydrocortisone (10(-9) to 10(-5) M) or other glucocorticoid hormones (dexamethasone, prednisolone, cortisone). Inhibition required the continued presence of the steroid. Removal of hydrocortisone (3 x 10(-7) M) after 4 days from endotoxin-treated cultures resulted in the rapid restoration of an endotoxin response, so that proteoglycan release approached maximum levels during a second 4-day culture period. Other C-21 steroid hormones (progesterone, aldosterone) were also inhibitory at 10(-5) M, but testosterone and beta-estradiol showed little influence on endotoxin action. Proteoglycan products of smaller average mol wt (Sepharose CL-2B chromatography), consistent with core protein cleavages, were released from endotoxin-treated cartilage. Cleavage was unaffected by beta-estradiol, partially blocked by aldosterone and largely prevented by hydrocortisone administration.
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PMID:Effect of steroid hormones on endotoxin-mediated cartilage degradation. 337 77

The influence of synovial fluid and serum from patients with inflammatory joint disease on proteoglycan metabolism was studied in organ culture of bovine nasal cartilage. Proteoglycan biosynthesis, i.e. incorporation of [35S]-sulphate, was reduced after addition of synovial fluid from rheumatoid arthritis and reactive arthritis patients. Also some rheumatoid arthritis sera but no reactive arthritis serum reduced the biosynthesis compared to control sera. Proteoglycan degradation, i.e. release of proteoglycans prelabelled with [35S]-sulphate, as well as release of proteoglycans determined by chemical methods, was highest under the influence of rheumatoid arthritis synovial fluid. This effect appears to represent an activity truly stimulating degradation, since added control serum did not prevent the effect. The lowest proteoglycan degradation was observed in culture medium only. Addition of synovial fluid compared to addition of control serum did not increase proteoglycan degradation in freeze-killed cartilage indicating that the effect requires living cells. The findings are consistent with the presence in synovial fluid of mediators stimulating the chondrocytes both to activate proteoglycan degradation and to reduce proteoglycan biosynthesis.
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PMID:Human arthritic synovial fluid influences proteoglycan biosynthesis and degradation in organ culture of bovine nasal cartilage. 339 7

To investigate mechanisms of cartilage destruction that may apply to rheumatoid arthritis, young and old human, and young porcine, articular cartilage was cultured for 8 days and the effects on proteoglycan (PG) metabolism of normal synovium supernatant (NSS), rheumatoid synovial fluid (RFL), and blood mononuclear cell supernatant (MCF) were studied. The effects were chondrocyte-mediated. An inverse correlation was found between baseline net PG synthesis and the effect of NSS on PG synthesis. Responses of young (porcine and human) cartilage were similar. In young cartilage the three agents induced PG depletion by suppression of net PG synthesis. In old cartilage NSS and RFL induced PG depletion, whereas MCF did not. In cartilage of low baseline net PG synthesis, NSS and MCF stimulated both PG release and PG synthesis; NSS stimulated predominantly PG release, and MCF predominantly PG synthesis. In conclusion, young and old human cartilage differ in the quality of their in vitro response to potentially catabolic factors. This may be due to the difference in baseline net PG synthesis. Synovial extracts differ from mononuclear-cell supernatants in their effects on old cartilage. It is suggested that this is caused by the presence, in different relative amounts, of factors that influence either PG synthesis or PG release.
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PMID:Differential responses of old human cartilage explants to synovial- and mononuclear-cell factors. 342 21

Proteoglycan concentrations in knee joint synovial fluid and in serum from patients with various inflammatory arthritides were studied using an enzyme-linked immunosorbent assay. Patients with reactive arthritis, calcium pyrophosphate arthropathy, and juvenile rheumatoid arthritis (age less than or equal to 20 years) had the highest synovial fluid concentrations. These values differed significantly (P less than 0.001) from those in patients with rheumatoid arthritis, psoriatic arthropathy, and chronic HLA-B27-associated arthropathy. Rheumatoid arthritis patients receiving low-dose prednisolone treatment had higher synovial fluid (P = 0.006) and serum (P less than 0.001) proteoglycan concentrations than did those taking nonsteroidal antiinflammatory drugs or slow-acting antirheumatic drugs. Serum proteoglycan concentrations were near the detection limits, and did not correlate with levels found in paired samples of knee joint synovial fluid. Patients with calcium pyrophosphate arthropathy had the highest mean serum level of proteoglycan. This assay of proteoglycan antigens is a useful tool in the study of proteoglycan metabolism in patients with joint disease. With its use, differences between disease groups and effects of therapy can be distinguished.
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PMID:Cartilage proteoglycans in synovial fluid and serum in patients with inflammatory joint disease. Relation to systemic treatment. 366 62

The purpose of this study was to clarify the mechanism of joint destruction in rheumatoid arthritis and osteoarthritis by observing the effects of the pathological synovial fluids on proteoglycan (PG) and collagen metabolism of chondrocytes. When chondrocytes from chick embryo were cultured with pathological synovial fluids, especially RA synovial fluid, biosynthesis of both proteoglycan and collagen of chondrocytes were found to increase in proportion to the amounts of pathological synovial fluids applied to the culture medium. Chondrocytes began to synthesize PG of small molecular size, approximately 70,000 in addition to PG of normal molecular size. It is noteworthy that the PG of small molecular size shows a shortening of the glycosaminoglycan link and core protein on undersulfation. These findings indicate that pathological synovial fluids disturb the biochemical regulation of the articular cartilage matrix by altering both PG and collagen metabolisms of chondrocytes.
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PMID:[Effects of pathological synovial fluids on the metabolism of chondrocytes]. 368 Oct 68

The purpose of this study was to test whether cartilage serves as the source or repository of antigenic components active in the stimulation of inflammation in rheumatoid arthritis through an analysis of peripheral blood lymphocyte proliferation. Articular cartilage samples were obtained from patients with osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis undergoing joint replacement surgery. Each sample was homogenized and characterized biochemically with respect to the content of proteoglycan, collagen, and immunoglobulin. Proteoglycan content of rheumatoid cartilage was reduced by 71% when compared to osteoarthritic cartilage; the proteoglycan content of ankylosing spondylitis cartilage was reduced by 40% when compared to osteoarthritic cartilage. Immunoglobulins were detectable in all cartilage samples when analyzed by ELISA or end-plate titration. Lymphocyte proliferation, quantified by uptake of 3H-thymidine, was unaltered by addition of cartilage fragments, low (saline) and high salt extracts (2.0 M CaCl2), or cartilage residues. Both autologous and heterologous lymphocytes were tested against the cartilage samples with no difference in reactivity. Purified bovine articular proteoglycans and Type II collagen were also inactive. Although tetanus toxoid and phytohemagglutinin were effective stimulants of proliferation, lymphocytes from arthritis patients were suppressed relative to those of normal individuals. Analysis of arthritic articular cartilage by these techniques failed to demonstrate the presence of antigen(s) stimulating proliferation of peripheral blood lymphocytes.
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PMID:Biochemistry and antigenicity of osteoarthritic and rheumatoid cartilage. 373 34

During inflammatory reactions, activated leukocytes are thought to produce a variety of small proteins (cytokines) that influence the behaviour of other cells (including other leukocytes). Of these substances, which include the interleukins, interferons and tumour necrosis factors (TNFs), interleukin-1 (IL-1) has been considered potentially a most important inflammatory mediator because of its wide range of effects. In vivo it is pyrogenic and promotes the acute phase response; in vitro it activates lymphocytes and stimulates resorption of cartilage and bone. Cartilage resorption is a major feature of inflammatory diseases such as rheumatoid arthritis, and IL-1 is the only cytokine hitherto known to promote it. TNFs are characterized by their effects on tumours and cytotoxicity to transformed cells, but share some actions with IL-1. I report here that recombinant human TNF alpha stimulates resorption and inhibits synthesis of proteoglycan in explants of cartilage. Its action is similar to and additive with IL-1, and it is a second macrophage-derived cytokine whose production in rheumatoid arthritis, or inflammation generally, could contribute to tissue destruction.
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PMID:Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage. 373 71

Hybridization of peripheral blood lymphocytes from patients with rheumatoid arthritis has yielded 14 monoclonal antibodies which react with cultured human epithelial cells. Immunofluorescence staining identifies at last five different types of antibody. Solid phase immunosorbent assays show a variety of cross-reaction patterns with nucleic acids, proteoglycan, cardiolipin and plastic, confirming that the various antibodies react with epitopes which are at least slightly different. These conclusions are confirmed by SDS gel electrophoresis and immunoblotting on epithelial cell extracts. Similar antibodies previously found in association with lupus-like disease have been thought to be representative of the high antinuclear antibody response characteristic of lupus. Our data are more consistent with the hypothesis that all or many of these antibodies are part of the normal inflammatory response.
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PMID:Human monoclonal antibodies from patients with rheumatoid arthritis: cross reactions against cellular constituents. 390


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