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)

Human chondrocyte proliferation and production of matrix components such as proteoglycans and type II collagen (coll. II) were studied in an in vitro model of differentiated chondrocytes. It clearly appears that several hormones such as growth hormone, calcitonin, androgens and parahormones such as insulin like growth factor I and epidermal growth factor stimulate chondrocyte proliferation and coll. II and proteoglycan synthesis. These hormones and parahormones have no effect on either prostaglandin production or release and activation of collagenase. From our investigations in vitro, articular chondrocytes are target cells for hormones and local factors mainly responsible of chondroformation.
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PMID:Effects of hormones and local growth factors on articular chondrocyte metabolism. 202 35

The nature and tissue distribution of non-collagenous bone proteins synthesized by adult rat bone marrow cells, induced to differentiate in the presence of dexamethasone (DEX) and beta-glycerophosphate (beta-GP), was studied in vitro to determine the potential role of these proteins in bone formation. Northern hybridization analysis revealed a strong induction of bone sialoprotein (BSP) and osteocalcin in DEX-treated cultures, whereas the constitutive expression of secreted phosphoprotein I (SPP-1), type I collagen, SPARC, and alkaline phosphatase was stimulated 6-, 5-, 3-, and 2.5-told, respectively. Metabolic labeling of proteins showed that the sialoproteins (SPP-1 and BSP) were mostly secreted into the culture medium in the non-mineralizing (-beta-GP) cultures, but were the predominant non-collagenous proteins associated with the hydroxyapatite of the bone nodules in mineralizing cultures (+ beta-GP). Extraction of the tissue matrix with 4 M GuHCl and digestion of the demineralized tissue matrix with bacterial collagenase revealed that some BSP was also associated non-covalently and covalently with the collagenous matrix. SPP-1 was present in two distinct, 44 kDa and 55 kDa, forms in the conditioned medium of all cultures and was preferentially associated with the hydroxyapatite in the mineralizing cultures. In comparison, SPARC was abundant in culture media but could not be detected in de-mineralizing extracts of the mineralized tissue. Radiolabeling with [35SO4] demonstrated that both SPP-1 and BSP synthesized by bone cells are sulfated, and that a 35 kDa protein and some proteoglycan were covalently associated with the collagenous matrix in +DEX cultures. Labeling with [32PO4] was essentially confined to the sialoproteins; the 44 kDa SPP-1 incorporating significantly more [32PO4] than the 55 kDa SPP-1 and the BSP. These studies demonstrate that BSP and osteocalcin are only expressed in differentiated osteoblasts and that most of the major non-collagenous bone proteins associate with the bone mineral. However, some novel proteins together with some of the BSP are associated with the collagenous matrix where they can influence hydroxyapatite formation.
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PMID:Expression of bone matrix proteins associated with mineralized tissue formation by adult rat bone marrow cells in vitro: inductive effects of dexamethasone on the osteoblastic phenotype. 203 18

Degradative enzyme (proteoglycanase and collagenase) as well as proteoglycan synthesis enzyme (glycosyl-transferase) activity was studied in osteoarthritic fibrillated cartilage. Proteoglycanase activity was significantly lower in 10 patients with hip osteoarthritis treated with Naproxen (1 g/daily for 4 weeks) than in 10 patients treated with acetaminophen. Synthesis enzyme activity was similar in both groups. The results which confirm in vitro studies suggest that naproxen has not toxic effect on human osteoarthritic cartilage and could rather be beneficial.
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PMID:[Effects of naproxen (naprosyne) on the metabolism of arthrotic cartilage in man in vivo]. 205 6

Human skin fibroblasts express, in addition to versican, a second large chondroitin sulfate/dermatan sulfate proteoglycan, which has been investigated with the aid of a specific antiserum in cultures of fetal fibroblasts. Its core protein, obtained after chondroitin ABC lyase treatment, exhibits an apparent molecular mass of about 740 kDa in the absence of a reducing agent whereas reduction produces two core proteins of 460 and 300 kDa, respectively. Both subunits carry one or very few dermatan sulfate chains of about 20 kDa which are of similar chemical composition irrespective of the type of subunits to which they are attached. Tryptic peptide maps of [35S]methionine-labeled core proteins indicated that both subunits are related neither to each other nor to versican, suggesting that the proteoglycan exists predominantly as a heterodimeric molecule. It is insensitive to collagenase and does not interact with hyaluronan. Pulse-chase experiments suggested that the core proteins are different gene products. Dimerization begins soon after core protein synthesis but requires more than 2 h for completion. Glycosaminoglycan synthesis occurs immediately prior to secretion. A small proportion of both subunits may be secreted in form of a monomeric proteoglycan. The heterodimeric proteoglycan is a major proteoglycan species of fetal fibroblasts. The secreted product represents 10-20% of [35S]methionine and about 5-10% of [35S]sulfate incorporated into secreted proteoglycans.
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PMID:A novel large dermatan sulfate proteoglycan from human fibroblasts. 207

The effect of transforming growth factor-beta (TGF-beta) on proliferation and differentiation of mouse clonal osteoblastic cells (MC3T3-E1) was examined in vitro in three different stages of their differentiation. Stage I (1-3 days after plating) was characterized by rapid cell growth, negligible alkaline phosphatase (ALP) activity and high proteoglycan synthesis, but low collagen production. In stage II (3-5 days after plating), proteoglycan synthesis sharply decreased and ALP activity and collagen synthesis began to increase. Stage III (7-9 days after plating) was characterized by maximal osteoblastic phenotypes. Treating MC3T3-E1 cells with 1 ng/ml of TGF-beta greatly inhibited DNA synthesis in stage I but not in stage II. In contrast, TGF-beta dose-dependently stimulated the synthesis of collagenase digestible proteins (CDP), noncollagenous proteins (NCP) and proteoglycan, especially in stage II. The minimum effective dose of TGF-beta in this stage was as low as 0.04-0.2 ng/ml. In stages I and III, the MC3T3-E1 cells were rather insensitive to TGF-beta in increasing three osteoblastic phenotypes. The increase in ALP activity in stages II and III was inhibited by 1 ng/ml of TGF-beta. These results indicate that the response to TGF-beta of mouse clonal osteoblastic MC3T3-E1 cells changes depending on their maturation stages.
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PMID:Transforming growth factor-beta modulates proliferation and differentiation of mouse clonal osteoblastic MC3T3-E1 cells depending on their maturation stages. 208 82

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

The role of articular chondrocytes and matrix degrading enzymes such as collagenase and neutral protease in the pathogenesis of quinolone-induced cartilage degeneration was investigated in immature guinea pigs. Articular cartilage from nalidixic acid (NA) treated guinea pigs was examined for the presence of protease activity or the ex vivo synthesis of collagenase at various times post-treatment. Histologic evaluation of knee joints confirmed the presence of degenerative changes in the matrix, but increased collagenase synthesis or protease activity were not detected. A separate group of animals was used to determine the importance of articular chondrocytes in the lesion generation. These cells were killed by intra-articular injection of the glycolysis inhibitor iodoacetic acid (IA) prior to treatment of the animals with NA. Typical "blister-like" their presence was not required for lesion development. Cartilage exposed to IA only did not exhibit "blister-like" lesions indicating that chondrocyte death and proteoglycan loss in conjunction with frictional forces associated with load-bearing were not sufficient to induce major matrical disruptive changes during the period of this study. These results indicate that articular chondrocytes are not actively involved in inducing the degenerative changes and provide no evidence for involvement of collagenase or neutral protease in the pathogenesis of the lesion.
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PMID:Passive role of articular chondrocytes in quinolone-induced arthropathy in guinea pigs. 216 70

In order to determine whether interleukin 6 (IL-6) is involved in the pathogenesis of the cartilage destruction observed in arthritis, the effect of human recombinant IL-6 on collagenase production and proteoglycan synthesis by bovine articular chondrocytes was examined. Addition of IL-6 (1.0 to 1000 U/ml) to the culture medium did not stimulate collagenase production or alter proteoglycan secretion. Whereas human purified interleukin 1 (IL-1) (20 U/ml) stimulated collagenase production and inhibited proteoglycan synthesis. Furthermore addition of IL-1 (20 U/ml) to chondrocyte cultures did not stimulate the chondrocytes to produce IL-6. Under our experimental conditions, IL-6 did not stimulate chondrocytes to proliferate as measured by [3H] thymidine incorporation. This would suggest that IL-6 is not involved in mediating cartilage loss.
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PMID:Comparison of the effect of interleukin 6 and interleukin 1 on collagenase and proteoglycan production by chondrocytes. 217 Jun 44

Conditioned culture medium derived from Interleukin-I alpha-activated human articular chondrocytes contained both collagen- and proteoglycan-degrading activities. Preparations of soluble type I collagen and the cartilage collagens type II, IX, X and XI were all degraded when incubated with the conditioned culture medium at 35 degrees C. Fractionation of the enzymic activities using column chromatography with Ultragel AcA 34 and Heparin-Sepharose allowed the separation and identification of neutral proteinase, collagenolytic and proteoglycan-degrading activities. Eluant fractions which contained type I collagenase activity effectively degraded collagen type II, but these fractions did not correspond precisely with those which degraded collagen types IX, X and XI. These observations indicate that chondrocytes have the potential to produce a conventional interstitial type II collagenase together with other enzymes having some specificity for the minor collagens. Thus IL-1-activated chondrocytes produce a range of collagenolytic and proteoglycan-degrading enzymes which can process most of the structural components of the cartilage matrix.
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PMID:Degradation of cartilage collagens type II, IX, X and XI by enzymes derived from human articular chondrocytes. 217 Aug 28

Conditions were established to stimulate human gingival fibroblast explant cultures to synthesize milligram quantities of the metalloproteinase proenzymes, prostromelysin and procollagenase. To stimulate enzyme production, cells were treated with 1 nM recombinant human IL-1 beta for approximately 7 days under serum free conditions. Using a combination of rapid column chromatography steps, approximately 10 milligrams of prostromelysin and 5 milligrams of procollagenase were purified from 1 liter of conditioned media. Prostromelysin electrophoresed as a doublet with molecular weights of 55,57 kD, whereas, procollagenase migrated with slightly lower molecular weights of 52, 54 kD. Both proenzymes were treated with trypsin or aminophenylmercuric acetate to generate active species. The molecular weights of the active enzymes were approximately 10 kD smaller than the proenzymes. Active enzymes were inhibited by metal chelators and the natural metalloproteinase inhibitor, tissue inhibitor of metalloproteinase (TIMP), but not by the serine protease inhibitor, phenylmethylsulfonyl fluoride (PMSF). Activated stromelysin degraded a number of substrates including transferrin, proteoglycan monomer, proteoglycan aggregated with hyaluronic acid, and substance P. By contrast, collagenase degraded interstitial type I collagen and the peptide thioester, Ac-Pro-Leu-Gly-SCH(iBu)Co-Leu-GlyOEt. Identity of both enzymes were confirmed by amino-terminal protein sequence analysis as well as by immunoblot analysis using monoclonal antibodies.
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PMID:Production and purification of prostromelysin and procollagenase from IL-1 beta-stimulated human gingival fibroblasts. 217 90


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