Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using EDTA extraction and collagenase digestion, cancellous bone from the femoral heads of ten normal and eight osteoarthrotic individuals was analyzed for its content of collagen, sialoprotein, proteoglycan, and carbohydrate. The EDTA extractability of the matrix proteins of the osteoarthrotic bone was significantly increased (P less than 0.001), as was the soluble collagenase-resistant fraction (SCRF). EDTA residues, bone matrix size, the collagenase-resistant fraction (CRF), and the insoluble collagenase-resistant fraction (ICRF) of the osteoarthrotic cases were not different from those of the controls. The amounts of carbohydrate and proteoglycans were considerably elevated in the bone matrix of the osteoarthrotic bone (P less than 0.01 and P less than 0.001, respectively). In the EDTA extracts, sialoprotein and proteoglycan contents were found in significant higher amounts (P less than 0.05 and P less than 0.01, respectively) in the osteoarthrotic cases. In the SCRF, the hexose and sialic acid contents were higher in the osteoarthrotic bone (P less than 0.01), while in the ICRF all the analyses were significantly increased in the osteoarthrotic bone (P less than 0.001). The ratios of collagen to non-collagenous components were lower in the osteoarthrotic than in normal bones. The quantitative and qualitative variations in cancellous bone proteins from the femoral head in osteoarthrosis found in this study suggest that alterations in subchondral bone play a role in the pathophysiology of cartilage degeneration in osteoarthrosis.
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PMID:Chemical composition of normal and osteoarthrotic cancellous bone of the femoral head. Studies of EDTA extracts and collagenase digests. 671 29

Recent reports on the Pond-Nuki model of osteoarthritis in the dog have provided evidence for partial disruption of the collagen network. The possibility of collagenase involvement in these localized changes was studied. Animals were killed 2, 4, 8, and 12 weeks after surgery. The left knee served as a sham-operated control. Cartilages from femoral condyles were processed for light and electron microscopy and assayed for collagenolytic activity by a direct tissue assay, based on the measurement of digestion of endogenous cartilage collagen. Animals killed at 2 and 4 weeks showed fibrillation and mild erosion of femoral condyles, which usually progressed to ulceration by 8 and 12 weeks. Electron microscopy demonstrated fiber disruption of the mid-zone perilacunar collagen as early as 2 weeks after the operation. Total collagenolytic activity, measured after activation by aminophenylmercuric acetate, was significantly higher in decreased cartilage than in controls of 2, 4, and 8 weeks; the peak value was at 4 weeks. Collagenase was shown, by its specific action on type I collagen, to be present at 2 and 4 weeks; however, other metalloproteases may also contribute to the digestion. The correlation between increased collagenolytic activity and the early osteoarthritic changes in cartilage suggests a role of this enzyme activity in the disease process.
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PMID:Collagenolytic activity and collagen matrix breakdown of the articular cartilage in the Pond-Nuki dog model of osteoarthritis. 687 Sep 69

The synovial fluids (SF) of patients with rheumatoid arthritis (RA) were investigated for their effects on thymocytes of C3H/HeJ mice. Of the 20 SF tested, 17 (85%) showed an augmentation of the phytohaemagglutinin (PHA) induced thymocyte stimulation. Out of 16 SF of patients with osteoarthrosis, such an activity was detected in only one (6.25%). Further characterisation of the amplification factor revealed that (1) the SF of RA patients augmented both the PHA and the Concanavalin A response of the thymocytes (2) in the absence of mitogens, SF-treated thymocytes showed an increased uptake of 3H-thymidine, (3) the SF did not propagate the growth of an interleukin 2 dependent ovalbumin specific T cell clone, but (4) the SF were found to be required for optimal interleukin 2 release by spleen cells stimulated with suboptimal doses of lectin. Based on these biological effects the factor in the SF of RA patients is suggested to represent an interleukin 1 (IL-1). IL-1 produced in cultures by activated macrophages has been shown to stimulate T and B cell functions and to induce the production of collagenase and prostaglandins by cultured synovial cells. Both properties of IL-1 could be relevant in the pathogenesis of RA.
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PMID:Interleukin 1 activity in the synovial fluid of patients with rheumatoid arthritis. 698 10

Resorption of cartilage matrix is usually considered to be due to extrinsic proteases, generally thought to be the neutral metalloproteases, including collagenase. Such enzymes can be secreted from synovial tissue and in acute forms of arthritis they are believed to be the main agents of pannus erosion. However, such enzyme secretion has not been clearly demonstrated to be the causative agent in either rheumatoid arthritis or in osteoarthritis. For example, no specific inhibitors of these proteinases have yet been proved effective in vivo. Recent experiments at the Strangeways Research Laboratory have demonstrated that viable chondrocytes of animal and human articular cartilage are capable of resorbing their surrounding matrix without the aid of extrinsic enzymes. We now know that such resorption can be stimulated by the action of a low molecular weight peptide released from living synovial and other connective tissues. These messengers (catabolins) are capable of stimulating chondrocytes to degrade totally both proteoglycan and collagen. The purification, properties, regulation and action of catabolism are under investigation to determine the role for catabolin in arthritis.
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PMID:Catabolin--a cartilage catabolic factor from synovium. 701 63

Cartilaginous wear particles were retrieved from synovial fluid aspirates of human diarthrodial joints and added to cultures of human or murine mononuclear phagocytes or human synovial cells. In each case, addition of the wear particles elevated the production of proteinases active at neutral pH against collage, gelatin, azocasein and the synthetic pentapeptide phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg. Synovial cells secreted more than five times as much collagenase as the same number of the other cells. All types of cell secreted significant quantities of enzymes active against the noncollagenous substrates. Mild treatment of the spent media with trypsin stimulated all of these eurmymic activities. The spent culture media of synovial cells which had been exposed to cartilaginous wear particles released hydroxyproline and glycosaminoglycan from powdered cartilage, indicating the production of enzymes which degrade both the collagen and proteoglycan of th cartilaginous matrix. Cultures of mononuclear phagocytes, in contrast, while solubilizing chondroitin sulphate from cartilage, released very little hydroxyproline. The ability of wear particles to elicit these effects suggests a role for them in the pathogenesis of osteoarthritis and other types of joint deterioration.
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PMID:Release of neutral proteinases from mononuclear phagocytes and synovial cells in response to cartilaginous wear particles in vitro. 702 35

The aim of this study was to validate a device developed previously to measure laxity of murine knee joints and to investigate whether experimentally induced pathological conditions result in measurable laxity. The laxity characteristics of normal murine knee joints were derived from measurements of 25 left knees of normal mice. Reproducible, nonlinear s-shaped load-displacement curves were determined, and parameters of anterior-posterior translation, varus-valgus rotation, and compliance were calculated from the curves. No differences were found between the left and right knee joints of eight mice. The average displacement between 0.8 N of anterior force and 0.8 N of posterior force was 0.47 +/- 0.10 mm. The endpoint compliances for anterior and posterior displacements were 0.16 +/- 0.03 and 0.16 +/- 0.04 mm/N, respectively. The average rotation between a 4 Nmm valgus moment and a 4 Nmm varus moment was 17.4 +/- 3.3 degrees. The endpoint compliances for varus and valgus rotations were 1.1 +/- 0.7 and 1.0 +/- 0.3 degrees/Nmm, respectively. Storage of the joints at -70 degrees C had no effect on laxity. We also studied the parameters of laxity after pathology of the knee joint was induced. Zymosan-induced or antigen-induced arthritis did not increase laxity of the joint. In an osteoarthritis model induced by injection of collagenase, laxity was markedly increased. In conclusion, laxity in the knees of mice can be measured reproducibly and changes in the characteristics of laxity due to pathological conditions can be quantified.
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PMID:Laxity characteristics of normal and pathological murine knee joints in vitro. 747 58

This article demonstrates that both the bulk water self-diffusion coefficient (D) and the spatially resolved variation in D for lesion canine cartilage due to osteoarthritis is increased by about 25% over that of surrounding cartilage. This increase in D can be mimicked by enzymatic degradation of cartilage with trypsin, hyaluronidase, and collagenase, or by mechanical means. However, it is established here using excised disks of living cartilage whose proteoglycan and collagen contents were manipulated by biochemical intervention in tissue culture that the diffusion measurement is not sensitive to the proteoglycan content of cartilage. Instead, self-diffusion appears to monitor mesoscopic (nonspecific) tissue damage. These results show that D, measured in a spatially resolved manner by pulsed field gradient nuclear magnetic resonance imaging, can localize regions of cartilage degradation.
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PMID:Self-diffusion monitors degraded cartilage. 748 94

The aim of this study was to examine the effects of 2 nonsteroidal anti-inflammatory drugs (NSAIDs), nimesulide and naproxen, on the proteoglycan matrix breakdown and metalloprotease synthesis of human osteoarthritic cartilage. The results showed that, under in vitro conditions, these 2 NSAIDs could significantly reduce both the degradation of proteoglycan and stromelysin synthesis. However, only nimesulide had the ability to significantly reduce collagenase synthesis. The effectiveness of these drugs on the natural course of osteoarthritis remains to be established by clinical studies.
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PMID:Effects of nimesulide and naproxen on the degradation and metalloprotease synthesis of human osteoarthritic cartilage. 750 92

A number of basic calcium phosphate crystals have been demonstrated in human articular tissues. The exact relationship between crystal deposition and disease remains obscure, although there is evidence supporting a rapid degenerative arthropathy within a specific set of patients. Limited reports of 'cuboid' calcium phosphate microcrystals in articular cartilage have been made over the last 10 years. In this study the occurrence of such crystals, not apparent by light microscopy, in human articular cartilage has been confirmed by transmission electron microscopy and X-ray microanalysis of tissue prepared by aqueous and anhydrous processing techniques. A crystal isolation technique involving collagenase digestion, centrifugation and sodium hypochlorite treatment was developed enabling crystal characterization by electron and X-ray diffraction. Crystals were identified as magnesium whitlockite; the first report of this mineral in articular cartilage. The presence of this mineral phase in normal and osteoarthritic articular cartilage is discussed with consideration given to physical conditions known to favor whitlockite formation and those extant in articular cartilage.
Osteoarthritis Cartilage 1995 Jun
PMID:The isolation and characterization of magnesium whitlockite crystals from human articular cartilage. 758 21

In rheumatoid and osteoarthritis, degradation of articular cartilage is mediated by the matrix metalloproteinases collagenase, stromelysin and gelatinase. The key event in this process is the cleavage of triple helical collagen by collagenase. We have determined the crystal structure of the catalytic domain of human recombinant fibroblast collagenase complexed with a synthetic inhibitor at 2.2 A resolution. The protein fold is similar to the amino termini of the zinc endopeptidases astacin thermolysin and elastase despite a lack of primary sequence homology. The conformation of the bound inhibitor provides a molecular basis for the design of inhibitors of collagenase and other matrix metalloproteinases. Such inhibitors should be useful in the treatment of a variety of diseases including arthritis and cancer.
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PMID:Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor. 765 13


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