Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Articular cartilage from arthritic joints of rats immunized with type II collagen is severely depleted of proteoglycans. Depletion begins within 48 hours after the onset of inflammation, prior to extensive pannus formation, and may represent a critical first step in cartilage destruction. We have immunolocalized stromelysin, an enzyme that is believed to play a major role in the pathologic degradation of proteoglycans, in the joints of rats with collagen-induced arthritis. Immunoperoxidase staining of frozen tissue sections demonstrated the presence of stromelysin in both the synovium and chondrocytes. In contrast, collagenase was localized primarily to the pannus-cartilage junction. Neither enzyme was detectable in joints from normal animals. To test the hypothesis that chondrocytes respond directly to inflammatory mediators by increasing the production of stromelysin, isolated chrondrocytes were incubated with various concentrations of interleukin-1. The culture media were also assayed for the presence of stromelysin by immunoreactivity on Western blots and by analysis of enzymatic activity on casein substrate gels. A 3-fold increase in a doublet of proteins synthesized in response to 10 units/ml of interleukin-1 was observed. These proteins also immunoreacted with the stromelysin antibody and degraded casein. Northern blotting results established that the increased levels of stromelysin were accompanied by increases in stromelysin-specific messenger RNA levels. These results suggest that stromelysin is responsible for proteoglycan degradation in early inflammatory arthritis, and that chondrocytes may play a direct role in the earliest stages of the degradation of their own matrices.
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PMID:The role of stromelysin in the cartilage destruction that accompanies inflammatory arthritis. 215 11

In this study, we determined the effects of indomethacin and calcitonin on bone resorption in otosclerosis-like lesions in rats. Morphometric analysis showed that both indomethacin and calcitonin inhibited active otosclerosis-like lesions (bone resorption) and rats immunologically induced with type II collagen, and indomethacin had a much higher inhibitory effect than calcitonin. In in vitro studies we found that conditioned medium from splenic lymphocytes of rats immunized with type II collagen stimulated collagenase production by macrophages and fibroblasts. Collagenase is the major enzyme for degradation of the organic components of bone. Treatment of the immunized rats with indomethacin and calcitonin significantly reduced the stimulatory effect of the lymphocyte-conditioned medium on collagenase production. Indomethacin caused a greater reduction of the stimulatory effect of the lymphocytes on collagenase production than calcitonin. These findings are in agreement with results of the morphometric study. Results of the present study also suggest that cell-to-cell interaction plays an important role in collagenase production for degradation of organic components of bone resorption in otosclerotic lesions.
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PMID:Effects of indomethacin and calcitonin on bone absorption in type II collagen-induced otosclerosis-like lesions in rats. 217 35

The activity of stromelysin and collagenase was determined in fibrillated human OA cartilage using labeled proteoglycans and type II collagen as substrates. In vitro paracetamol had no effect on metalloprotease whereas TA induced a significant inhibition of stromelysin. In cartilage and synovium from nine patients treated with TA and nine patients treated with paracetamol during 8 weeks before surgery for hip OA, stromelysin activity was significantly lower in the TA than in the paracetamol group. The results suggest that TA has a potential chondroprotective effect in OA.
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PMID:Cartilage degradative enzymes in human osteoarthritis: effect of a nonsteroidal antiinflammatory drug administered orally. 231 5

A T cell line specific to human type II collagen (CII) was selected and propagated from DBA/1J mice immunized with human CII. The line cells were not reactive to type I or type III collagen of human origin, but they were cross-reactive to bovine, rat, and rabbit CII and they recognized both native and heat-denatured human CII. The cells were reactive to an N-terminal three-quarters fragment of human CII, produced by tadpole collagenase digestion of human CII, but not to a C-terminal one-quarter fragment of human CII. The cells showed Thy-1+, Lyt-1+, Lyt-2-, and L3T4+ phenotypes characteristic of T helper cells or delayed-type hypersensitive cells, determined by the immunofluorescence method. To clarify the role of T cells in the pathogenesis of collagen-induced arthritis, we inoculated this cell line into DBA/1J mice and found that they developed clinical arthritis, albeit at a low incidence. The cells attenuated by x-ray were capable of inducing resistance to the subsequent induction of collagen-induced arthritis of DBA/1J mice. The sera from mice protected by inoculation of the cell line exhibited anti-idiotypic antibody response against conventional and monoclonal anti-CII antibodies. Anti-T cell receptor response may be involved in the mechanism for the protective effect of the cell line against autoimmune murine arthritis.
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PMID:Isolation of T cell line capable of protecting mice against collagen-induced arthritis. 244 73

Chondrocytes from bovine articular cartilage were stripped of matrix, then allowed to reconstitute their pericellular matrix in suspension culture. After incubation, the cells were centrifuged through a Percoll (TM) cushion and separated into a cell fraction, a medium fraction, and an interface fraction. The collagen in each fraction was analyzed by SDS-polyacrylamide gel electrophoresis and immunolocation with antisera against type XI and type II. Under these conditions, type XI collagen was recovered in the cell fraction, but was not detectable by immunolocation in the medium fraction or the interface fraction. In contrast, type II collagen was found in all three of these fractions. Insoluble type XI fibers subjected to the same fractionation scheme in the absence of cells were recovered in the medium and interface fractions, but not in the cell fraction. Incubation of intact cells with collagenase digested the cell-associated collagen, indicating that it was outside of the cells. The type XI collagen was removed from the cells by extraction with 4 M guanidinium chloride. These results indicate that type XI collagen is preferentially retained at the chondrocyte surface, and are consistent with our proposal that it is involved in organization of the pericellular matrix.
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PMID:Type XI collagen is associated with the chondrocyte surface in suspension culture. 250 10

Chick-derived native cartilage collagen type X and the pepsin-resistant 45 kDa fragment were susceptible to attack by human synovial collagenase and neutrophil elastase at 25 degrees C and 35 degrees C. Synovial collagenase cleaved type X collagen at two sites which were equally susceptible to the enzyme. In contrast, elastase produced three cleavages, but the sensitive loci showed different susceptibilities as judged by the sequential appearance of specific breakdown products. Both enzymes produced a major, enzyme-resistant fragment of approximately 32 kDa at 35 degrees C, and both of these end-products co-migrated in SDS polyacrylamide gels. Human chondrocyte-derived collagenase also degraded native, 59 kDa collagen type X in a similar manner to that shown by the synovial collagenase. From amino acid sequence data the enzyme cleavages probably occur at three regions of sequence imperfection. The specific cleavages brought about by synovial or chondrocyte collagenase, or neutrophil elastase, may have a functional catabolic role in vivo, and in vitro might provide useful tools with which to further analyse specific properties of the native collagen type X molecule.
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PMID:Cleavage of collagen type X by human synovial collagenase and neutrophil elastase. 254 40

Phospholipase A2 (PLA2) activity was measured in articular cartilage from normal and osteoarthritic (OA) human femoral heads. Protoglycanase and collagenase activity was determined in the same specimens using radiolabelled human proteoglycan subunit and type II collagen, respectively. Grossly normal and fibrillated OA cartilage samples showed a significant increase in PLA2 activity which was not found in osteophytic cartilage. PLA2 activity was found to be correlated with proteoglycanase but unrelated to collagenase activity. Tiaprofenic acid induced in vitro a concomitant increase in PLA2 and a decrease in proteoglycanase activity. PLA2 which may be activated by cytokines as well as mechanical factors is suggested as a key enzyme in chondrocyte metabolism regulation. Tiaprofenic acid is shown as a potential chondroprotective nonsteroidal anti-inflammatory drug.
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PMID:Phospholipase A2 activity in human osteoarthritic cartilage. 234 43

Collagenases are known to be associated with tissue destruction in chronic inflammatory diseases such as periodontal diseases and rheumatoid arthritis. Collagenases are secreted by circulating inflammatory cells (polymorphonuclear leukocytes and monocytes), resident mesenchymal cells and epithelial cells in latent forms, which can be activated by proteases and compounds reacting with protein thiol groups. We have studied here the effects of oxygen-derived free radicals (ODFR) on latent human neutrophil collagenase. Also, in order to elucidate the cellular sources of collagenases, the ability of human gingival crevicular fluid (GCF) collagenases both from adult periodontitis (AP) and localized juvenile periodontitis (LJP) patients to degrade soluble interstitial collagen types I and II was studied. ODFR generated by the xanthine oxidase/hypoxanthine system in the presence of trace amounts of iron and EDTA activated latent neutrophil collagenase to an equal extent as the known activators phenylmercuric chloride and gold thioglucose. ODFR activation was inhibited by desferoxamine and mannitol as well as by superoxide dismutase and catalase. Clear differences in the susceptibility of collagen types I and II to AP and LJP GCF collagenases were observed. AP GCF collagenase degraded type I and II collagens at equal rates, resembling the substrate-specificity of human neutrophil collagenase. LJP GCF collagenase degraded type I collagen considerably faster than type II collagen, which was only negligibly degraded. This corresponds to the substrate specificity of fibroblast collagenase. Zymographic evaluation of gelatinolytic proteases showed the presence of 90 and 68 kD gelatinases in both AP and LJP GCF. Non-proteolytic means apparently provide a potent activation pathway of neutrophil collagenase in vivo and the hydroxyl radical was identified to be one of the potent activating oxidants.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Non-proteolytic activation of latent human neutrophil collagenase and its role in matrix destruction in periodontal diseases. 256 61

Calvaria from 20-21 day old fetuses were obtained under sterile conditions and the endo- and exoperiosteum stripped off. Cells were dispersed by sequential collagenase-DNase treatment and suspended in 0.5% low Tm agarose in the presence of DMEM supplement with 10% FCS. After 4-5 days of incubation some 30% of these cells showed active synthesis of metachromatic extracellular matrix. Cells from skin, muscle and periosteum failed to show metachromatic matrix positive colonies to a comparable extent. The phenotypic expression of these cells was determined by analysis of collagen types. Eleven day old cultures were incubated in the presence of [3H]-proline plus beta-aminopropionitrile and ascorbic acid and the collagen extracted analyzed by polyacrylamide electrophoresis of their intact chains or CNBr-derived peptides. The results show that anchorage independence is a requirement for calvaria cells to express type II collagen. Type I collagen was preferentially expressed in monolayer culture or when pre-attached to a substrate before being cultured in agarose. Type II collagen was the predominant collagen when cells were cultured in agarose. Further characterization of cell populations was achieved by isopycnic centrifugation in a percoll gradient. Cell fractions were tested for their collagen phenotype when cultured in agarose. Cells recovered from densities 1.04 g/ml or higher synthesized type II collagen, while cells with densities lower than 1.04 g/ml synthesized mainly type I collagen. Isopycnic centrifugation appears to be a novel method for separation of phenotypically different cells from a heterogeneous population in fetal calvaria. The high density cell fractions may represent a mixture of pre-chondrocytes as well as pluripotential cells.
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PMID:Cells isolated from fetal rat calvaria by isopycnic separation express different collagen phenotypes. 271 31

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.
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PMID:Evaluation of a modified hexose sugar, amiprilose hydrochloride, in experimental models of synovitis. 278


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