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)

Autoimmunity to collagen was investigated in several naturally occurring arthropathies of the dog. Increased levels of serum anti-native collagen type II antibody, as assessed by ELISA, were shown in 72.4% of dogs with rheumatoid arthritis (RA), 88% of dogs with infective arthritis (IA) and 52% of dogs with osteoarthritis (OA) (p less than 0.001). The mean levels of antibody in cruciate disease patients (CR) were also significantly increased compared to control dogs (p less than 0.01). Serum anti-collagen antibody in OA dogs correlated with that in precipitated serum immune complexes. There was also a correlation between anti-collagen antibody level in synovial fluid and in synovial fluid complexes in dogs with rupture of the cranial cruciate ligament. In all patient groups, collagenase digestion of polyethylene glycol (PEG) precipitates from sera and synovial fluids caused a significant rise in specific antibody levels to collagen, indicating the presence of collagen-anti-collagen complexes in all arthropathies. In dogs with RA, the levels of collagen-specific antibody in synovial fluid complexes correlated with the total IgG in these complexes. These findings implicate collagen-anti-collagen complexes in the pathogenesis of naturally occurring joint diseases in the dog, but they are unlikely to be the primary aetiological mechanism.
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PMID:Anti-type II collagen antibody in naturally occurring canine joint diseases. 259 Aug

Osteoarthritis was induced in 12 normal dogs by severing of the anterior cruciate ligament of the right knees, the left knees serving as sham operated controls. The animals were killed at 7 and 14 weeks postsurgery. The total hexuronate, and thus proteoglycan, content of the articular cartilage of operated knees remained unaltered during the period of study. After pretreatment with a highly purified collagenase and in the presence of selected protease inhibitors, a higher proportion of the tissue hexuronate could be extracted from the different topographical areas of osteoarthritic joints under non dissociative conditions (70-75% versus 55-65% for control knees). The nondissociatively recovered osteoarthritic proteoglycans (a-A1 preparations) displayed progressive and consistent changes in their sedimentation profile. First, the size of the fast sedimenting or more saturated aggregates appeared to be reduced in the different regions of osteoarthritic joints at 7 weeks postoperatively. The disappearance of the faster sedimenting mode as well as a dramatic increase in the proportion of monomers were only detected in the topographical zones exhibiting the most severe surface damage and histologic abnormalities at 14 weeks postsurgery. The proteoglycan molecules present as "free" or "nonaggregated" monomers in a-A1 preparations recovered from normal and osteoarthritic cartilage at different time periods after surgery were separated from their corresponding aggregates by rate zonal centrifugation in isokinetic cesium sulfate gradient. Although they were severely depleted in keratan sulfate, the purified "free" and "aggregated" osteoarthritic monomers appeared to be normal in terms of aggregating capacity and size distribution, and were therefore not degraded. This progressive changes in size distribution of proteoglycan aggregates in the early stages of experimental canine osteoarthritis could contribute significantly to the biochemical and biomechanical alterations of osteoarthritic cartilage.
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PMID:Changes in the sedimentation profile of proteoglycan aggregates in early experimental canine osteoarthritis. 263 43

The growth of synovial fibroblast-like cells from patients with rheumatoid arthritis and rats with streptococcal cell wall (SCW)-induced arthritis in vitro under anchorage-independent conditions is inhibited by transforming growth factor-beta (TGF-beta). Because this growth factor is present in rheumatoid synovial fluids, we studied whether this cytokine might be secreted by cells in rheumatoid synovial tissue. We show that synovial tissues from patients with rheumatoid arthritis and osteoarthritis, and rats with SCW-induced arthritis, contain TGF-beta-1 mRNA. TGF-beta, predominantly type 1, was spontaneously secreted in vitro by synovial tissue explants and synovial fibroblast-like cells. In addition, TGF-beta could be detected immunohistochemically in cells throughout rheumatoid and SCW-induced arthritic rat synovial tissues. Finally, exogenous TGF-beta induced collagen and inhibited collagenase mRNA levels by cultured synoviocytes. These data support an autocrine role for TGF-beta in the regulation of synoviocytes in rheumatoid arthritis and, in light of its demonstrated effects on the immune system, suggest that TGF-beta might also have important paracrine effects on infiltrating inflammatory cells.
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PMID:Transforming growth factor-beta production by synovial tissues from rheumatoid patients and streptococcal cell wall arthritic rats. Studies on secretion by synovial fibroblast-like cells and immunohistologic localization. 266 90

Collagenase has been implicated in the pathogenesis of several arthropathies. Arteparon [glycos-aminoglycan (GAG) polysulfate] is a proteinase inhibitor that is being investigated as a therapeutic agent in osteoarthritis. We found that cultures of calcified lapine synovium release collagenase, one tenth of which is already activated. Normal synovium produces no active collagenase. GAG polysulfate suppresses the amount of active collagenase by one half. GAG polysulfate may interfere with the activation process of collagenase.
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PMID:Suppression of active collagenase from calcified lapine synovium by Arteparon. 282 15

Osteoarthritis is characterized by a loss of articular cartilage due at least in part to the action of degradative enzymes secreted by chondrocytes. We have investigated the effect of type II collagen from cartilage and interleukin 1 on collagenase production in cultures of rabbit articular chondrocytes. Interleukin 1 alone stimulated the chondrocytes to secrete collagenase but this response was increased as much as fivefold by the addition of rabbit type II collagen. Bovine type II and chick type I collagens were also stimulatory. The native form of the collagens was not required since denatured collagens and purified chick type II alpha chains were effective. The observed effects of collagens and interleukin 1 may contribute to the progressive nature of osteoarthritis.
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PMID:The stimulation of collagenase production in rabbit articular chondrocytes by interleukin-1 is increased by collagens. 282 8

We found the presence of collagenase-like (CL) peptidase in synovial fluid by a highly sensitive fluorescence assay using (succinyl-Gly-Pro-Leu-Gly-Pro)-4-methyl-coumaryl-7-amide (Suc-GPLGP-MCA) as a substrate. Suc-GPLGP-MCA is hydrolyzed at the Leu-Gly bond by CL-peptidase. The CL-peptidase activity in synovial fluid was significantly higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA) and in arthropathy-free controls. No significant difference in CL-peptidase activity in synovial fluid was found between patients with OA and arthropathy-free controls.
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PMID:Collagenase-like (CL) peptidase activity in synovial fluid from patients with rheumatoid arthritis. 283 60

Native serum C1q, the collagenous-like subcomponent of the first component of complement, is not recognized by polyclonal anti-collagen type II antibodies. However, when purified C1q was subjected to limited proteolysis by collagenase it showed antigenic cross-reactivity with collagen type II. The same cross-reactivity was observed with hemolytically active C1q in synovial fluids of patients with rheumatoid arthritis (RA), whereas C1q from synovial fluids of patients with osteoarthritis (OA), villo-nodular synovitis and ankylosing spondylitis was not recognized by this antibody. However, incubation of synovial fluid C1q of OA patients with synovial fluid leucocytes from RA patients led to an alteration of OA-C1q which was now recognized by the anti-collagen type II antibody.
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PMID:Enzymatic alteration of C1q, the collagen-like subcomponent of the first component of complement, leads to cross-reactivity with type II collagen. 283 Jan 44

The number of leucocytes and the concentrations of protein, proteoglycans (PG), elastase a1 proteinase inhibitor complexes (E-alpha 1 Pi) and collagenolytic activity were measured in the synovial fluid (SF) of 15 patients with rheumatoid arthritis (RA) and 18 with osteoarthritis (OA). The mean levels of protein, E-alpha 1 Pi and collagenase and the number of leucocytes were higher in RA than in OA SF. However, the mean level of PG was higher of OA SF than in RA. In the latter, they were principally in the form of monomers and fragments while in the former they were in the form of aggregates and monomers. There was a direct relationship between the concentration of E-alpha 1 Pi and either the number of white cells or the concentration of synovial proteins, suggesting that the measurement of E-alpha 1 Pi complexes is a biochemical index of the local inflammatory reaction. There was an inverse correlation between the concentrations of PG and E-alpha 1 Pi which may reflect the effect of degradation in PG of elastase and other enzymes released at the same time. Finally, there was a direct relationship between the concentration of E-alpha 1Pi and collagenase which may be the reflection of a simultaneous release of various enzymes from leucocytes and macrophages.
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PMID:Measurement of proteoglycans, elastase, collagenase and protein in synovial fluid in inflammatory and degenerative arthropathies. 298 25

In osteoarthritis, despite increased matrix synthesis, there is a reduction of both major matrix components, proteoglycan and collagen. This study suggests that this is the result of enhanced degradative activity intrinsic to the cartilage. Because osteoarthritis is a focal disease, histologic controls were used to measure the severity in different areas of the cartilage and in different specimens. Neutral proteoglycanase and collagenase were both described in human cartilage, and their levels matched the severity of the disease as did acid phosphatase, a marker of lysosomal enzymes. Articular cartilage collagenase has an inhibitor in the cartilage and has negligible activity in normal cartilage. This was found not to be a lysosomal enzyme. A model of osteoarthritis was studied and found to have the same biochemical pattern as human disease. Using this method, inhibitors of degradative enzymes were used as a treatment. The chelator of metallic cations EDTA was found to have a significant effect on reduction of degradative enzyme activity and altered the arthritic process.
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PMID:Degradative enzyme systems in osteoarthritic cartilage. 298 65

The levels of kallikrein and collagenase in synovial fluid from rheumatoid arthritis (RA) patients were examined and the role of kallikrein in procollagenase activation is discussed. Both prekallikrein and active kallikrein in synovial fluid from patients with RA were significantly elevated when compared to synovial fluid from patients with osteoarthritis (OA). In RA synovial fluid, the ratio of the active form to total kallikrein was also higher than that in OA synovial fluid. Both active collagenase and the alpha 2-macroglobulin (alpha 2M)-collagenase complex in RA synovial fluid were higher than in OA synovial fluid. A partial correlation (r = 0.58) between active kallikrein and total collagenase (active and alpha 2M-collagenase complex) was observed in RA synovial fluid. These observations indicate that both kallikrein and collagenase are associated with the destruction of cartilage, but the role of kallikrein in procollagenase activation was not fully clarified.
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PMID:Kallikrein in synovial fluid with rheumatoid arthritis. 303 90


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