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)

The distribution of ossified collagen (bone) and uncalcified collagen (fibrous tissue and cartilage) was compared histologically for rat and dog calvaria at birth. The relative amount of bone and uncalcified collagen was quantitated morphologically for rat calvaria during the first four weeks of rapid growth. Whereas dog calvaria are essentially ossified at birth, rat calvaria at birth consist mostly of fibrous tissue but rapidly become ossified with growth. Bacterial collagenase was used to separate uncalcified collagen from calcified collagen of whole membranous bones (frontal and parietal) and long bones (femur and humerus) at birth from man, monkey, dog, guinea pig, rabbit and rat. By this means quantitative changes in the relative fractions of the two forms of collagen were determined during the first eight weeks of postnatal growth for each type of rat bone. Quantitative biochemical data on whole rat bones (calvarium, femur, humerus) confirmed measurements based on histology which showed that at birth rat calvaria are mostly uncalcified as compared to other species whose bones are mostly ossified at birth. With growth rat membranous bones ossify more rapidly than long bones.
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PMID:Comparison of whole calvarial bones and long bones during early growth in rats. Histology and collagen composition. 16 16

Bone matrix and tendon are compared in terms of their carbohydrate and non-collagenous protein composition. The collagen content of both tissues was similar (90-91%), but bone matrix had at least three times as much sialic acid (0.28%) as tendon (0.08%). Smaller differences were found in the analysis of hexoses and hexosamines. After digestion with bacterial collagenase, about 9% of the total protein from both tissues was non-diffusible on dialysis, and this contained only 0.15% (bone) and 0.7% (tendon) of the original hydroxyproline; recovery of sialic acid was 86-87%. The collagenase-resistant soluble material amounted to about 9% (bone matrix) and 5% (tendon); the insoluble residues were 1 and 4% respectively. There were clear differences in the carbohydrate contents of the digests, but the amino acid compositions were similar. When the soluble digests were chromatographed on DEAE-cellulose, the elution profiles indicated the presence in each tissue of a variety of glycoproteins and a proteoglycan fraction, and showed clearly that an acidic glycoprotein corresponding to bone sialoprotein was not present in tendon.
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PMID:A comparison of bone matrix and tendon with particular reference to glycoprotein content. 18 11

The increase of total collagen and its destruction were compared for whole calvaria and long bones from young growing rats prelabeled in utero with 3H-L-proline. Rats were compared from birth to 16 weeks of age. Long bones and calvaria were isolated as intact anatomical units for autoradiography or separated by collagenase into calified and uncalcified collagens. Autoradiography using 14C-L-proline demonstrated eccentric modeling of bone collagen. With growth the mass of calcified collagen (bone) increased rapidly in calvaria and long bones. A similar increase in the mass of uncalcified collagen (mainly cartilage) occured in the long bones; a very small increase occurred in the fibrous tissue of calvaria. Total and specific radioactivities of collagens at each age were compared to that present at birth. With growth remodeling an almost complete loss of pre-existing radioactive collagen occurred from uncalcified fibrous tissue of calvaria as compared to a smaller but substantial loss from the uncalcified cartilage of long bones. A marked loss of calcifed collagen occurred in long bones as compared to a smaller loss from calvarial bones. The istopic data indicate a large turnover of fibrous tissue (type I collagen) with growth remodeling as compared to a smaller turnover of bone (calcified, type I collagen) and cartilage (typc I collagen). The turnover rate of skeletal collagens depends upon whether the collagen is calcified or not, and not upon the type of collagen.
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PMID:Comparison of whole calvarial bones and long bones during early growth in rats. II. Turnover of calcified and uncalcified collagen masses. 126 Apr 88

We studied the effect of mast cell chymase on the interaction between osteoblasts and extracellular matrix. Chymase was purified from mast cell lysate by anion exchange chromatography. Osteoblasts were isolated from rat calvarias by collagenase digestion. Incubation of osteoblasts with mast cell lysate (40-170 micrograms/ml) or purified chymase (8-32 micrograms/ml) resulted in changes in cell-matrix interaction and cell morphology. Osteoblasts treated with chymase also showed a gradual detachment from the artificial substrata and from the biomatrix (collagen-digested rib fragment). A similar effect of mast cell chymase on the osteoblasts was found in vitro on endosteum of an intact parietal bone. Neutral protease inhibitors abolished the effect of both crude and purified enzyme preparations on the cell-matrix interaction. Mast cell chymase had no effect on osteoblast viability. The effect of enzyme on osteoblast proliferation was studied with lower concentrations of enzyme (0.2 micrograms/ml) in order to avoid cell detachment; there was no effect on either the metaphase index or on the number of cells after 5 days of incubation with chymase. Osteoblast attachment and cell spreading on different matrix proteins (fibronectin, vitronectin, extract of noncollagenous matrix proteins from rat bone) were significantly altered by their pretreatment with chymase. Matrix fibronectin of osteoblasts in culture as well as soluble vitronectin and fibronectin were digested by rat mast cell chymase. Our data suggest that mast cells through action of neutral protease chymase may alter molecules in extracellular matrix that are important in osteoblast adhesion, cell spreading, maintenance of cell morphology, and, most likely, cell function.
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PMID:Interaction of osteoblasts with extracellular matrix: effect of mast cell chymase. 768 44

The triterpenes, alpha-amyrin (AA) and its palmitate (AAP) and linoleate esters (AAL), were tested on models of inflammatory and destructive arthritic processes and their effects were compared with the clinical antiarthritic drugs indomethacin (IN) and methotrexate (MTX). The triterpenes had no effect on the prostaglandin phase of carrageenin pedal edema in rats, which was reduced 28% by 100 microM IN. AAL caused a considerable reduction in the synthesis by human neutrophils of 5-lipoxygenase products--5-HETE (IC50 = 70 microM), LTB4, (62 microM), isomer I (30 microM) and isomer II (24 microM). Rat osteosarcoma cell growth was inhibited by all triterpenes with IC50's (microM) of < 10 (AAP), 14 (AA) and 27 (AAL) and were more effective than IN (35). MTX caused 100% inhibition at a concentration of 10 microM compared with 64% inhibition by AAP. Tadpole collagenase digestion of type I (bone) native collagen was completely inhibited by all the triterpenes as well as IN and MTX at 100 microM. The results indicate that the principal point of antiarthritic intervention by amyrin triterpenes lies in their local inhibition of joint destruction.
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PMID:Antiarthritic mechanisms of amyrin triterpenes. 795 94

Osteoclasts degrade bone matrix, which is mainly type I collagen and hydroxyapatite, in an acidic extracellular compartment. Thus we reasoned that osteoclasts must produce an acid collagenase. We purified this enzyme, a 31 kDa protein, from avian osteoclast lysates (in 100 mM acetate/1 mM CHAPS/1 mM dithiothreitol, pH 4.4), fractionated by (NH2)2SO4 precipitation, gelatin-affinity, cation exchange, and gel filtration. Fraction activity was measured using diazotized collagen or 3H-labelled cross-linked collagen (decalcified and trypsin-treated metabolically L-[4,5-3H]proline-labelled bone) as substrates. Iodoacetate, leupeptin, antipain, pepstatin and mercurials inhibited collagenolysis by the isolated proteinase; mercurial derivatives could not be re-activated by dithiothreitol. Collagen degradation was maximal at pH 4.4; purified proteinase reproduced the collagenolytic activity of cell lysates. The N-terminal amino acid sequence from the isolated protein and its CNBr degradation fragments showed sequence similarity to mammalian cathepsin Bs, and near-identity with avian liver cathepsin B. Peptide substrate specificity of the osteoclastic enzyme resembled those of mammalian cathepsin B and its avian liver counterpart, but degradation of low-molecular-mass substrates by the osteoclastic enzyme was slower, reflecting generally lower kcat. values. Further, kcat/Km varied less between arginine-containing substrates than for previously reported cathepsin Bs, indicating different substrate specificity of the osteoclast enzyme. Polyclonal antibody raised to a 25 kDa fragment of the enzyme recognized a single 31 kDa band in SDS/PAGE of osteoclast lysates blotted to poly(vinylidene difluoride), adsorbed collagenolytic activity of osteoclast lysates, and stained avian osteoclasts in tissue sections. Degenerate sense- and antisense-oligonucleotide primers, predicted from segments of primary amino acid sequence, amplified a 486 bp DNA fragment; this was cloned and sequenced. Of 162 amino acids encoded, 77% are identical with those of human cathepsin B; hybridization identified a 2.4 kb RNA in osteoclast lysates. We conclude that the major avian osteoclast collagenolytic enzyme is a cathepsin B, whose activity varies from other enzymes of its class.
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PMID:Extracellular-matrix degradation at acid pH. Avian osteoclast acid collagenase isolation and characterization. 845 15

Our aim was to investigate the collagenolytic potential and localization of matrix metalloproteinase-2 (MMP-2) in relation to its regulatory proteins membrane type MT1-MMP and tissue inhibitor of metalloproteinases-2 (TIMP-2) in rheumatoid arthritis (RA). For this purpose, we have used purification of MMP-2, MMP-8, MMP-9 and interstitial type I, II and III collagens; SDS-PAGE/densitometric collagenase activity assay; zymography; Western blotting; reverse transcriptase polymerase chain reaction; in situ hybridization; and immunofluorescence, ABC, ABC-APAAP double immunostainings. MMP-2 degraded human type II collagen almost as effectively as MMP-8, whereas MMP-9 did not cleave type II collagen. In synovial tissue, MT1-MMP, TIMP-2 and MMP-2 were found in synovial lining in fibroblast- and macrophage-like cells, in stromal cells and in vascular endothelium. MT1-MMP, TIMP-2 and MMP-2 were strongly expressed in the pannocytes of the invasive pannus at the interface, but staining was weak and/or there were few positive cells both "above" and "below" the soft-to-hard tissue (cartilage and/or bone) interface. Rheumatoid synovial tissue extract contained proteolytically active 62/59 kDa MMP-2 and 43 kDa MT1-MMP, but no free TIMP-2. These results indicate that components of the ternary MT1-MMP/TIMP-2/MMP-2 complex are coexpressed in the normal synovial lining and in its pathological extension on the hyaline articular cartilage. MMP-2 may participate in the remodeling of the normal lining and also seems to be localized/focalized to pannocytes at a site critical for tissue destruction in arthritis.
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PMID:New collagenolytic enzymes/cascade identified at the pannus-hard tissue junction in rheumatoid arthritis: destruction from above. 992 52

A. actinomycetemcomitans has clearly adapted well to its environs; its armamentarium of virulence factors (Table 2) ensures its survival in the oral cavity and enables it to promote disease. Factors that promote A. actinomycetemcomitans colonization and persistence in the oral cavity include adhesins, bacteriocins, invasins and antibiotic resistance. It can interact with and adhere to all components of the oral cavity (the tooth surface, other oral bacteria, epithelial cells or the extracellular matrix). The adherence is mediated by a number of distinct adhesins that are elements of the cell surface (outer membrane proteins, vesicles, fimbriae or amorphous material). A. actinomycetemcomitans enhances its chance of colonization by producing actinobacillin, an antibiotic that is active against both streptococci and Actinomyces, primary colonizers of the tooth surface. The fact that A. actinomycetemcomitans resistance to tetracyclines, a drug often used in the treatment of periodontal disease, is on the rise is an added weapon. Periodontal pathogens or their pathogenic products must be able to pass through the epithelial cell barrier in order to reach and cause destruction to underlying tissues (the gingiva, cementum, periodontal ligament and alveolar bone). A. actinomycetemcomitans is able to elicit its own uptake into epithelial cells and its spread to adjacent cells by usurping normal epithelial cell function. A. actinomycetemcomitans may utilize these remarkable mechanisms for host cell infection and migration to deeper tissues. A. actinomycetemcomitans also orchestrates its own survival by elaborating factors that interfere with the host's defense system (such as factors that kill phagocytes and impair lymphocyte activity, inhibit phagocytosis and phagocyte chemotaxis or interfere with antibody production). Once the organisms are firmly established in the gingiva, the host responds to the bacterial onslaught, especially to the bacterial lipopolysaccharide, by a marked and continual inflammatory response, which results in the destruction of the periodontal tissues. A. actinomycetemcomitans has at least three individual factors that cause bone resorption (lipopolysaccharide, proteolysis-sensitive factor and GroEL), as well as a number of activities (collagenase, fibroblast cytotoxin, etc.) that elicit detrimental effects on connective tissue and the extracellular matrix. It is of considerable interest to know that A. actinomycetemcomitans possesses so many virulence factors but unfortunate that only a few have been extensively studied. If we hope to understand and eradicate this pathogen, it is critical that in-depth investigations into the biochemistry, genetic expression, regulation and mechanisms of action of these factors be initiated.
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PMID:Virulence factors of Actinobacillus actinomycetemcomitans. 1052 26

Women are more susceptible to anterior cruciate ligament (ACL) injuries than men performing similar athletic activities. Because tissue remodeling may affect ligament strength, we assessed expression of tissue remodeling effector genes in the human ACL. Specifically, we surveyed ACL for RNAs encoding all known matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteases (TIMPs) by reverse transcription/polymerase chain reaction (RT-PCR). These experiments revealed that mRNAs encoding nine of sixteen MMPs and all four TIMPs are present in the normal ACL. The nine expressed proteases were MMPs 1-3, 7, 9, 11, 14, and 17 (collagenase 1, gelatinase A, stromelysin 1, matrilysin, gelatinase B, stromelysin 3, and membrane types 1 and 4, respectively), and MMP-18. Genes for MMPs 8, 10, 12, 13, 15, and 16 appeared not to be expressed in ACL, as their mRNAs were not detected using RT-PCR conditions that did yield positive signals from other tissues (testis or bone). We conclude that numerous genes encoding tissue remodeling effector proteins are expressedin the human ACL.
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PMID:Expression of matrix metalloprotease and tissue inhibitor of metalloprotease genes in human anterior cruciate ligament. 1151 74

Osteoarthritis (OA) is one of the most common joint diseases among adults, and its early detection is still not possible. In this study, high-frequency ultrasound and ultrasound-assisted mechanical testing systems were used to quantitatively measure the morphologic, acoustic and mechanical properties of normal and enzymatically degraded bovine articular cartilages in vitro. A total of 40 osteochondral cartilage plugs were prepared from 20 bovine patellae (n=20x2) and divided into two groups for collagenase and trypsin digestions, respectively. A high-frequency ultrasound system (center frequency: 40 MHz) was used to analyze the surface integrity (ultrasound roughness index, URI), thickness and acoustic properties of the articular cartilages before and after enzymatic degradations. Acoustic parameters included the integrated reflection coefficient (IRC) from the cartilage surface, reflection from the cartilage-bone interface (AIB(bone)), integrated attenuation (IA) and integrated backscatter (IBS) of the internal cartilage tissue. A newly developed ultrasound water jet indentation system was used to assess the mechanical properties of the cartilage samples. The results showed that the URI increased significantly (p<0.05) after collagenase digestion while no significant change (p>0.05) was found after trypsin digestion. With regard to acoustic parameters, the IRC decreased significantly (p<0.05) after collagenase digestion while no significant change (p>0.05) was found after trypsin digestion. The AIB(bone) demonstrated an insignificant change after collagenase digestion (p>0.05) but a significant decrease after trypsin digestion (p<0.05). Both enzymatic degradation groups showed insignificant differences (p>0.05) in the IA but a significant increase (p<0.05) in the IBS after both enzymatic degradations. The apparent stiffness measured by ultrasound water jet indentation suggested that articular cartilage from both groups became significantly softer (p<0.05) after the enzymatic degradations. A significant relationship was found to exist between the IRC and URI (p<0.05). This study showed that high-frequency ultrasound can be a comprehensive tool to quantitatively and systematically analyze the morphologic, acoustic and mechanical properties of articular cartilage in association with its degeneration.
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PMID:Quantitative assessment of articular cartilage with morphologic, acoustic and mechanical properties obtained using high-frequency ultrasound. 2017 50


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