Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The growth of synovial fibroblast-like cells from patients with rheumatoid arthritis and rats with streptococcal cell wall (SCW)-induced arthritis in vitro under anchorage-independent conditions is inhibited by transforming growth factor-beta (TGF-beta). Because this growth factor is present in rheumatoid synovial fluids, we studied whether this cytokine might be secreted by cells in rheumatoid synovial tissue. We show that synovial tissues from patients with rheumatoid arthritis and osteoarthritis, and rats with SCW-induced arthritis, contain TGF-beta-1 mRNA. TGF-beta, predominantly type 1, was spontaneously secreted in vitro by synovial tissue explants and synovial fibroblast-like cells. In addition, TGF-beta could be detected immunohistochemically in cells throughout rheumatoid and SCW-induced arthritic rat synovial tissues. Finally, exogenous TGF-beta induced collagen and inhibited collagenase mRNA levels by cultured synoviocytes. These data support an autocrine role for TGF-beta in the regulation of synoviocytes in rheumatoid arthritis and, in light of its demonstrated effects on the immune system, suggest that TGF-beta might also have important paracrine effects on infiltrating inflammatory cells.
 ...
PMID:Transforming growth factor-beta production by synovial tissues from rheumatoid patients and streptococcal cell wall arthritic rats. Studies on secretion by synovial fibroblast-like cells and immunohistologic localization. 266 90

Inflammatory and 'non-inflammatory' forms of arthritis affect a large proportion of the population and these diseases can often lead to disability. Although the pain of arthritis can be relieved to some extent by the peripherally acting aspirin-like drugs, the progression of disease leading to joint destruction is largely resistant to current drug therapy. The synovial joints of patients with rheumatoid arthritis are infiltrated with neutrophils, macrophages and lymphocytes and the resident cells become activated to degrade the cartilage and bone. The inflammatory and destructive changes that occur are brought about by the action of mediators or local hormones which are produced by a variety of cell-types. Lipid mediators, such as prostaglandins, contribute to the symptoms of arthritis while polypeptide cytokines, such as interleukin 1 and tumour necrosis factor, play a key role in joint destruction by activating the synovial cells and chondrocytes to release metalloproteinases, such as collagenase. Aspirin-like drugs inhibit the production of prostaglandins from inflamed tissues and thereby blunt the symptoms of arthritis. However, these drugs do not suppress the production of collagenase from connective tissue cells and, therefore, do not halt the degeneration of joint tissues.
 ...
PMID:Pathogenesis and treatment of chronic arthritis. 269 74

Amiprilose HC1 (SM-1213), a nontoxic modified hexose sugar, was evaluated in in vivo and in vitro models of synovitis. In 8 sequential trials, 90 Louvain (LOU) rats and 91 Sprague-Dawley (SD) rats were immunized with chick type II collagen and given amiprilose HC1 in water (1 mg/ml) or water alone. In the LOU rats, the arthritis incidence was 7/46 (15%) in the amiprilose HC1 group vs 16/44 (36%) in the water group (p less than 0.01). In the SD rats, the incidence was 28/46 (60%) in the experimental vs 33/45 (73%) in the control group (p greater than NS), although the prevalence of arthritis on Days 16 and 21 was significantly (p less than 0.03) lower in the experimental group. Amiprilose HC1 did not affect the antibody titers or delayed-type hypersensitivity to collagen, or T cell subset distribution in the LOU experiments. Two analogues, SM-1211 and SM-1212, did not alter this disease. No toxicity was noted. At a nontoxic concentration of 1 mg/ml, amiprilose HC1 suppressed 3H thymidine incorporation in cultured rabbit synovial fibroblasts by 78% and resulted in the appearance of numerous intracytoplasmic granules/vacuoles. These effects were partially antagonized by indomethacin or dexamethasone at 10(-7) M. SM-1211 was inert in this system. Amiprilose HC1 system also reduced rabbit synoviocyte supernatant prostaglandin E2 levels up to 73% in a dose related fashion, but did not affect collagenase activity. These morphologic changes in synoviocytes, combined with anti-inflammatory and antiproliferative effects, provide evidence that amiprilose HC1 possesses modest and nontoxic antirheumatic properties. A search for analogues of this sugar with more substantial clinical activities is warranted.
 ...
PMID:Evaluation of a modified hexose sugar, amiprilose hydrochloride, in experimental models of synovitis. 278

Articular chondrocytes cultured in the presence of recombinant human interleukin 1 alpha (rhIL-1 alpha) or recombinant human tumor necrosis factor alpha (rhTNF alpha) caused increased production of the latent metalloproteinase (collagenase and caseinase) and the proteoglycan release from cartilage. The existences of IL-1 and TNF alpha in the chondrocytes of human articular cartilage were also shown by immunohistochemical staining using polyclonal antibodies. Furthermore, chondrocyte was found to be a producer of interleukin 6 (IL-6), known as a pleiotropic cytokine and thought to be an important mediator of the cell interactions in arthritis. In addition, the production of IL-6 was also shown to be stimulated by rhIL-1 alpha or rhTNF alpha. From our findings, we suggest there exists a very complicated autocrine control system of chondrolysis by the chondrocyte itself.
 ...
PMID:The role of cytokines in chondrocyte mediated cartilage degradation. 281 Feb 94

Rabbit proactivator is a neutral metalloproteinase that activates another metalloproteinase, procollagenase, and degrades noncollagenous matrix. We describe the construction of an activator complementary DNA (cDNA) clone, which is 1.9 kb, that selects a 2.1-kb messenger RNA (mRNA) in Northern blot hybridizations. Nucleic acid sequence studies of the activator cDNA indicate 1) that it encodes protein Mr 53,881, 2) that this protein exhibits approximately 80% homology with rat transin, an oncogene-induced protein with a previously unknown function, and 3) that, in the first 172 residues, it is virtually identical to the rabbit metalloproteinase, stromelysin. Homology between rabbit activator and human skin collagenase is approximately 50%. Activator and collagenase mRNA are coordinately regulated; untreated cultures of rabbit synovial fibroblasts produce low levels of each protein, but addition of phorbol myristate acetate (10(-8)M) results in an increase in mRNA for both proteins by 2.5-5 hours. Adding all-trans-retinoic acid (10(-6)M) or dexamethasone (10(-7)M) to phorbol-stimulated cells coordinately suppresses both activator and collagenase mRNA. Our data suggest the existence of coordinately regulated metalloproteinases that are important in the modulation of connective tissue metabolism.
Arthritis Rheum 1987 Nov
PMID:Cloning of a complementary DNA for rabbit proactivator. A metalloproteinase that activates synovial cell collagenase, shares homology with stromelysin and transin, and is coordinately regulated with collagenase. 282 26

The activity of elastase and collagenase was measured in the synovial fluid (SF) of 24 patients with inflammatory and 6 patients with traumatic joint effusions. The enzyme activity was compared with local and systemic variables of the disease. Elastase and collagenase activity could be detected in 79 and 83%, respectively, of the arthritic SF, whereas no enzyme activity was found in the traumatic joint effusions. The SF enzyme activity showed no correlation with clinical, laboratory or radiographic variables of arthritis in the joint from which the fluid was obtained. Our results show that proteolytic enzyme activity in SF may help to distinguish inflammatory from noninflammatory joint effusions but does not reflect the severity of the arthritic process.
 ...
PMID:Elastase and collagenase activities in synovial fluid of patients with arthritis. 282 14

Synthetic calcium pyrophosphate dihydrate crystals and, to a lesser extent, synthetic hydroxyapatite crystals increased the amount of interleukin-1/mononuclear cell factor released by human blood monocytes, as measured by collagenase and prostaglandin E2 production by rabbit chondrocytes, human dermal fibroblasts, and adherent rheumatoid synovial cells. The same crystals also directly induced collagenase and prostaglandin E2 secretion by rabbit chondrocytes, and potentiated the action of interleukin-1/mononuclear cell factor on chondrocytes. These mechanisms may be important in the pathogenesis of the destructive arthropathies associated with these crystals.
Arthritis Rheum 1987 Dec
PMID:Effect of synthetic calcium pyrophosphate and hydroxyapatite crystals on the interaction of human blood mononuclear cells with chondrocytes, synovial cells, and fibroblasts. 282 29

We studied synovial fluid (SF) collagenase in 10 women with severe rheumatoid arthritis (RA), 10 with pyrophosphate arthropathy, and 10 with idiopathic destructive disease of the shoulder conforming to a pattern recently described. SF cell counts were highest in the RA group. Particles were detected by polarized light microscopy and alizarin red staining. Crystals were seen in fluids from all 3 groups; pyrophosphate predominated in the pyrophosphate arthropathy group and alizarin red-positive particles in the idiopathic disease group. Collagenase and tissue inhibitor of metalloproteinase levels were estimated in SF after gel filtration. Tissue inhibitor of metalloproteinase activity was detected in all fluids, but tended to be highest in the RA group. Collagenase activity was detected in 3 RA fluids only. In no sample was collagenase found in an active form. These findings support the clinical concept of an aggressive destructive process which sometimes occurs in the shoulder joints of elderly women. Because we were not able to detect free collagenase in SF from any of the patients with idiopathic shoulder disease, the data suggest that high levels of active collagenase are not characteristic of this group of patients.
Arthritis Rheum 1988 Jul
PMID:Synovial fluid collagenase in patients with destructive arthritis of the shoulder joint. 284 85

Clones of dermal fibroblasts from the skin of 4 normal subjects and 5 patients with progressive systemic sclerosis (PSS; scleroderma) were established, and their synthetic and proliferative characteristics were compared. A limiting-dilution assay was used to determine frequencies of cloning in the microcultures of dermal fibroblasts plated. The clones derived from single cells were expanded in vitro and examined (in passages C-H) for growth and synthesis of glycosaminoglycan (GAG) and collagenase-sensitive protein (CSP). The clonogenicity of PSS fibroblasts was not significantly different from that of normal fibroblasts. Normal fibroblast clones were characterized by low levels of GAG and CSP synthesis, and there was a correlation between the GAG and CSP phenotypes. In contrast, clones of PSS fibroblasts were often, but not always, high producers of GAG and CSP, but there was no correlation between the levels of GAG and CSP synthesis. It appears that scleroderma skin is composed of fibroblast clones that are unable to regulate the synthesis of connective tissue components and often synthesize large amounts of connective tissue macromolecules.
Arthritis Rheum 1988 Oct
PMID:Heterogeneous synthetic phenotype of cloned scleroderma fibroblasts may be due to aberrant regulation in the synthesis of connective tissues. 284 98

Growing evidence suggests that biochemical mechanisms play a role in the pathogenesis of arthritis. Cartilaginous wear particles have been shown to induce destructive enzymes and cytokines. To assess the biocompatibility of artificial ACL replacements, the effects of wear particles from the following ligaments were analyzed biochemically and histologically: GORETEX, Stryker Dacron Ligament Prosthesis, Versigraft carbon, Kennedy LAD, Xenograft, Leeds-Keio, and human patellar tendon allograft. Ligaments were frozen and ground to produce wear particles similar to those seen clinically and were added to lapine synovial cell cultures. The resulting conditioned medium was analyzed for collagenase, gelatinase, and chondrocyte activating factor (CAF) production. All of the ligaments induced significantly elevated enzyme and CAF production by the synoviocytes, with Xenograft and carbon inducing significantly higher enzyme levels than those of the other five ligaments. Five milligrams of wear particles were injected into the knees of 4 kg to 5 kg rabbits that were analyzed histologically after 14 weeks. Wear particles accumulated in the periarticular synovial folds and induced modest to severe macrophage infiltration in the synovium. A hypothetical model explaining the role of artificial ligament wear particles in the pathogenesis of arthritis is presented.
 ...
PMID:The biochemical and histological effects of artificial ligament wear particles: in vitro and in vivo studies. 285 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>