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)

Collagen autoimmunity has been suggested as one etiologic mechanism to otosclerosis. Although substantial studies relating this disease to collagen autoimmunity have been reported, a basic understanding of the pathogenic mechanism involved is lacking. Some otosclerosis patients have a high level of antibody to type II collagen. In addition, complement and antibody were deposited in the stapes from otosclerosis patients. Furthermore, the otic capsule and stapes have been found to contain type II collagen by immunohistologic studies and biochemical analysis. Otospongiosis-like lesions have also been produced in rats by immunizing them with type II collagen. This finding led us to postulate a hypothesis of an autoimmunity to type II collagen as an etiopathogenesis of this illness. Our initial hypothesis has been updated to incorporate new findings in the field of cell biology. The role of interleukin 1, osteoclasts, osteoblasts, bone resorption, and other factors such as minor collagens, calcitonin, vitamin D, parathyroid hormone, collagenase, and prostaglandins are incorporated in this updated hypothesis.
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PMID:Enchondral cartilage rests collagen-induced autoimmunity: a possible pathogenetic mechanism of otosclerosis. 350 78

Matrix vesicles (MV) can be readily isolated from culture media of chicken growth plate hypertrophic chondrocytes grown in primary culture. The chondrocytes maintain normal morphology and synthesize type II collagen throughout the culture period. The culture-derived MV are morphologically indistinguishable from MV seen in situ and are rich in alkaline phosphatase. Formation of alkaline phosphatase-rich MV is strongly influenced by the stage of culture: large numbers are released shortly after cell seeding; marked decline is seen during cell spreading and rapid cell division; notable resurgence in alkaline phosphatase-rich MV production occurs as the cells attain confluency. Increasing the initial chondrocyte seeding density proportionately increases MV production. Cells derived from the hypertrophic region are much more capable of forming alkaline phosphatase-rich MV than those from the proliferating zone, indicating that MV formation is dependent on cellular differentiation. MV released by the cultured chondrocytes were compared in protein and phospholipid composition and in their ability to accumulate mineral ions, with plasma membrane fractions and collagenase-released MV obtained from the same tissue. Electrophoretic patterns of proteins, and the phospholipid profiles, suggest that significant modification of the plasma membrane occurs during MV formation. The vesicles are capable of accumulating large amounts of mineral ions from a metastable synthetic cartilage lymph when supplied with alkaline phosphatase substrates. This culture system thus appears to be a useful model for isolating native MV and characterizing factors required for vesicle formation and mineralization.
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PMID:Isolation and characterization of calcium-accumulating matrix vesicles from chondrocytes of chicken epiphyseal growth plate cartilage in primary culture. 390

Cartilage was taken from the macroscopically normal part of human femoral heads immediately after orthopedic surgical operations for total prothesis consecutive to hip arthrosis. After clostridial collagenase digestion and repeated washings, chondrocytes (10(6) cells) were cultivated in a gyrotory shaker (100 rpm). Under these conditions, cells were kept in suspension and after 3 to 5 d formed a flaky aggregate which, on Day 10, became dense. These chondrocytes were morphologically differentiated: they had a round shape, were situated inside cavities, and were surrounded by a new matrix. Histochemical methods showed the presence of collagen and polysaccharides in cell cytoplasm and in intercellular matrix, and the immunofluorescence method using specific antisera (anticartilage proteoglycans and anti-type II collagen) showed that these two constituents were in intercellular matrix. The measurement of the amounts of proteoglycans (PG) released into culture medium and those present in chondrocyte aggregate (by a specific PG radioimmunoassay) showed a maximum production on Days 3 to 5 of culture, then the production decreased and stabilized (from Day 10 to the end of culture). The observed difference between the amounts of PG in aggregates after 20 d and those after 2 h of culture demonstrated that PG neosynthesis did occur during cultivation. This conclusion was supported by other results obtained by [14C]glucosamine incorporation in chondrocyte aggregates. Moreover, the aggregate fresh weight related to cell number (appreciated by DNA assay) increased significantly with culture duration. Three-dimensional chondrocyte culture represents an interesting model: chondrocytes were differentiated morphologically as well as biosynthetically and synthesized a new cartilage matrix.
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PMID:Human chondrocytes in tridimensional culture. 394 76

We have maintained chick embryo chondrocytes in culture for more than 2 months, passaging the floating cells in the absence of ascorbic acid. Throughout the culture period some of the cells attached to the dish, assuming an epithelial-like morphology and subsequently giving rise to new floating cells. The interconversion of the two cell populations was highest in primaries and decreased with the aging of the culture. Cartilage cells synthesized pro-alpha 1 (II) collagen and sulphated proteoglycans in vitro; compared with floaters, the epithelial-like cells secreted relatively large amounts of fibronectin. When ascorbic acid was added to the medium, all cells attached, maintaining their rounded shape; in this condition the pro-alpha, (II) collagen was matured and collagen fibres were detectable outside the cells. Other specific proteins synthesized by the chondrocytes in culture were also identified. One of these, a 64 K collagenase-sensitive protein, was not related to the type II collagen and may represent a new collagen type.
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PMID:The culture of chick embryo chondrocytes and the control of their differentiated functions in vitro. I. Characterization of the chondrocyte-specific phenotypes. 621 15

Degradation of type II and III collagens by tadpole collagenase in a mixture of both substrates was monitored by SDS-polyacrylamide gel electrophoresis in 3 M urea, followed by densitometric quantiation. The degradation rates of type II and III collagens were increased and decreased, respectively, by the mutual prsence, compared with those of type II and III collagens alone. The results suggest that the degradation of type II collagen in vivo may be regulated by the presence of other type(s) of collagen, particularly in such a case as resorption of cartilage in the region of newly forming osteoid tissue.
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PMID:Degradation rates of type II and III collagens by tadpole collagenase are modulated by mutual presence. 624 1

Culture media collected from secondary monolayer and spinner cultures of rabbit articular chondrocytes showed evidence of collagenolytic activity by the following criteria: (1) Amicon PM-10 concentrates of culture medium released [14C] glycine from reconstituted rabbit skin collagen fibrils at 37 degrees C; (2) medium concentrated by lyophilization decreased the relative viscosity of human cartilage collagen in solution. The loss in viscosity was partially inhibited if medium was preincubated with o-phenanthroline, and (3) degradation of human cartilage collagen after 60 h incubation at 24 degrees C was characterized primarily by the appearance of 75 000 dalton (TCA) and 25 000 dalton ((TCB) products. The majority of the collagenase (EC 3.4.24.3) from cultured chondrocytes was secreted in latent form, since preincubation with either trypsin or p-aminophenylmercuric acetate significantly increased activity against human cartilage collagen. Chondrocyte collagenase may be important in mediating the normal slow turnover of cartilage collagen and may be particularly active in collagen destruction associated with early stages of synovial joint arthritides, before attack by non-cartilage cells or extra-articular soft tissues.
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PMID:Neutral proteinases from articular chondrocytes in culture. I. A latent collagenase that degrades human cartilage type II collagen. 626 Feb 4

The separation and further purification of human polymorphonuclear-leucocyte collagenase and gelatinase, using modifications of the method of Cawston & Tyler [(1979) Biochem J. 183, 647-656], are described. The final preparations yielded collagenase of specific activity 260 units/mg and gelatinase of specific activity 13 000 units/mg. Gelatinase was purified to apparent homogeneity in a latent form, and analysis of the activation of 125I-labelled latent enzyme by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and gel-filtration techniques suggested that no peptide material was lost on conversion into the active form. The purified natural inhibitors alpha 2-macroglobulin, tissue inhibitor of metalloproteinases ('TIMP') and amniotic-fluid inhibitor of metalloproteinases all inhibited the two polymorphonuclear-leucocyte metalloproteinases, but the last two inhibitors were slow to act and complete inhibition was difficult to attain. Collagenase degraded soluble types I and III collagen equally efficiently, but soluble type II collagen less well. Gelatinase alone had little activity on these substrates, although it enhanced the action of collagenase. Gelatinase was capable of degrading soluble types IV and V collagen at 25 degrees C, whereas collagenase was only active at higher temperatures when the collagens were susceptible to trypsin activity. By using tissue preparations of insoluble collagens (type I, II or IV) the activity of leucocyte collagenase was low and gelatinase activity was negligible, as measured by the solubilization of hydroxyproline-containing material. The two enzymes together were two or three times more effective in the degradation of these insoluble collagens.
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PMID:Partial purification of collagenase and gelatinase from human polymorphonuclear leucocytes. Analysis of their actions on soluble and insoluble collagens. 628 93

Kinetic analysis of the degradation of mixtures of type I and type II collagens by tadpole collagenase was performed, using [14C]glycine-labeled type I collagen and [3H]acetylated type II collagen as substrates. The degradation rate of type I collagen was decreased in the initial stage of the reaction, then further slowed down giving a constant rate independent of both the amounts of enzyme and type II collagen. The effect of type II collagen on the degradation of type I collagen is two-fold. First, competitive inhibition manifested only in the initial stage of the reaction due to higher (about 4-fold) affinity of type II collagen for the enzyme than type I collagen. Second, interference in step(s) following the formation of enzyme-substrate complex.
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PMID:Dual effects of type II collagen on the degradation of type I collagen by tadpole collagenase. 628 28

In addition to releasing collagenase and proteoglycanase activity, rabbit articular chondrocytes in monolayer culture released into the culture medium, latent, neutral enzyme activity which when activated by p-aminophenylmercuric acetate degraded fluorescein-labeled polymeric rat tail tendon Type I collagen and the tropocollagen TCA and TCB fragments of human Type II collagen into smaller peptides at 37 degrees C. Enzyme activity was abolished if p-aminophenylmercuric acetate-activated culture medium was preincubated with 1.10-phenanthroline, a metal chelator. Thus, articular chondrocytes in monolayer culture are capable of producing neutral proteinases which acting together can result in complete degradation of tendon and cartilage collagen to small peptides.
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PMID:'Gelatinase-like' activity from articular chondrocytes in monolayer culture. 629 87

Blood mononuclear cells from patients with rheumatoid arthritis produce the lymphokine, leukocyte inhibitory factor (LIF) in response to collagens in vitro, and blood monocytes release prostaglandins (PGE2) and a factor, mononuclear cell factor (MCF) which stimulates collagenase and PGE2 production by cultured synovial cells. We therefore examined the effect of collagens on the production of PGE2 and MCF. Blood mononuclear cells from 6 patients with rheumatoid arthritis and 6 normal subjects were cultured in native human types I, II, or III collagen-coated tubes, or with streptokinase-streptodornase (SK-SD), and the supernatant media derived from these cultures analyzed for the presence of MCF, PGE2, and LIF. Types II and III collagens, as well as SK-SD, markedly stimulated MCF production by the cells from all 12 subjects (MCF activity, expressed as a mean stimulation index (SI) +/- SEM, was 43 +/- 12 for type II, 33 +/- 7 for type III, and 37 +/- 23 for SK-SD). Type I collagen was less stimulatory (mean SI 10 +/- 7). Cells from the patients with rheumatoid arthritis, but not the normal subjects, produced LIF in response to types II or III collagens but not to type I collagen. PGE2 production by blood mononuclear cells paralleled that of MCF, although abrogation of PGE2 release with indomethacin did not reduce MCF production. alpha chains purified from denatured collagens also stimulated MCF production. Using cells from patients with rheumatoid arthritis, type II collagen stimulated production of all three factors in the presence of polymyxin B or fibronectin-depleted serum, suggesting, respectively, that neither endotoxin nor fibronectin were responsible for their generation. Monocytes, purified from normal blood by an adherence technique, but not lymphocytes depleted of monocytes, released MCF and PGE2 when cultured with type II collagen. These results demonstrate that collagens can act as ligands to stimulate monocytes, as well as antigens to stimulate sensitized lymphocytes, to produce soluble factors that may contribute to the destruction of connective tissue.
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PMID:Collagens act as ligands to stimulate human monocytes to produce mononuclear cell factor (MCF) and prostaglandins (PGE2). 630 48


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