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)

A number of cells, chemotactic factors, and inflammatory mediators are implicated in the complex mechanisms underlying crystal-mediated inflammation. Interleukin-8, released from mononuclear cells that have been exposed to urate and other crystals, is a potent chemotaxin and activator of neutrophils. Experimental and clinical observations suggest that joint movements, local biomechanical factors, and previous joint damage may play a role in influencing the intensity of microcrystalline synovitis and the distribution of articular and periarticular crystal deposits in both calcium pyrophosphate dihydrate crystal deposition disease and gout. There are rare reports of extra-articular calcium pyrophosphate dihydrate crystal deposition in tendons, bursae, dura mater, and ligamentum flavum (with radiculomyelopathy) and of massive "tumoral," tophuslike, periarticular calcium pyrophosphate dihydrate crystal deposits. Synovial fluid levels of ATP, the main substrate for nucleoside triphosphate pyrophosphohydrolase ectoenzyme, which cleaves ATP-releasing inorganic pyrophosphate, are higher in patients with calcium pyrophosphate dihydrate crystal deposition disease than in those with other arthritides, and the levels correlate with inorganic pyrophosphate concentrations. Further reports of acute calcific periarthritis of the first metatarsophalangeal joint (hydroxyapatite pseudopodagra) in young women have been described. The mitogenic response of fibroblasts to stimulation with basic calcium phosphate crystals is accompanied by induction and secretion of collagenase and neutral proteases, implicating a role for the crystals in the pathogenesis of both synovial proliferation and joint damage in chronic basic calcium phosphate crystal-associated arthropathy. Subcutaneous cholesterol crystal deposition with tophus formation is extremely rare and has been described in a patient with scleroderma and calcinosis cutis.
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PMID:Calcium pyrophosphate crystal deposition disease and other crystal deposition diseases. 150 84

Although collagen-containing implants are widely used in various surgical applications, there has been relatively little attention paid to the possibility that this type of biomaterial may undergo pathologic calcification which could compromise its function. The present study reports for the first time the calcification of a series of implants of purified collagen sponges prepared with graded degrees of aldehyde-induced cross-linkages (assessed by shrinkage-temperature, wetting time, and collagenase digestibility). Type I collagen sponges were pretreated with either glutaraldehyde (0.1% to 2.0% aqueous solution, for 5-180 minutes) or formaldehyde (as vapors for 15 minutes to 15 hours), and implanted subcutaneously for 21 days in weanling rats. Although specimens not pretreated with either aldehyde reagent and the formaldehyde sponges pretreated for 15 minutes were resorbed without evidence of calcification, all other aldehyde-pretreated implants mineralized. The degree of calcification did not correlate with extent of cross-linking. Formaldehyde-pretreated implants calcified more extensively (Ca2+ = 87.8 +/- 2.8 micrograms/mg, mean +/- standard error of the mean; n = 58) than did glutaraldehyde-pretreated implants (Ca2+ = 40.9 +/- 1.4 micrograms/mg; n = 52). It is concluded that both glutaraldehyde- and formaldehyde-pretreated Type I collagen sponges calcify after subdermal implantation in young rats. Although aldehyde pretreatment of Type I collagen sponge implants is a prerequisite for their eventual mineralization, the threshold level of aldehyde-induced cross-linking required to potentiate their maximal pathologic calcification is low.
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PMID:Calcification of subcutaneously implanted type I collagen sponges. Effects of formaldehyde and glutaraldehyde pretreatments. 307 59

Pathologic calcification is thought to be the main cause of failure in the present generation tissue valves fabricated from glutaraldehyde pretreated bovine pericardium (BP). The present investigation describes the in vitro calcification and enzymatic degradation of bovine pericardia after hexamethylene diisocyanate (HMDIC) crosslinking and subsequent modification with polyethylene glycol. The enzymatic degradation of these treated surfaces were monitored by scanning electron micrography and tensile strength measurements. Various proteases, such as alpha-chymotrypsin, bromelain, esterase, trypsin and collagenase were investigated for tissue stability. Incubation of these enzymes with crosslinked pericardia had variably reduced their tensile strength. Among these treated surfaces, polyethylene glycol (PEG) grafted BP via isocyanate functionalities had retained maximum strength. The PEG modified tissues had also indicated a substantial reduction in calcification, when compared to other treated tissues. Further, the biocompatibility of various pericardial tissues were established by platelet adhesion and octane contact angle measurements. It is assumed that the PEG modification of pericardium may interfere with the cellular activation of injury (platelets) to reduce tissue associated calcification. In conclusion, it seems the PEG modification of bovine pericardium via HMDIC may provide new ways of controlling tissue biodegradation and calcification. However, more in vivo studies are needed to develop applications.
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PMID:The anticalcification effect of polyethylene glycol-immobilized on hexamethylene diisocyanate treated pericardium. 1170 61

The susceptibility of meniscus allografts to enzymatic degradation may be reduced through tissue stabilization. We have previously reported on an epoxide-based crosslinker, triglycidyl amine (TGA), which can be used alone or with a bisphosphonate (MABP) to stabilize heterograft heart valves and reduce their pathologic calcification. Our objective was to evaluate the effects of TGA and TGA-MABP pretreatment on an orthopedic allograft involving meniscus crosslinking, degradation, calcification, and compressive properties. Ovine menisci treated with TGA or TGA-MABP for up to seven days and glutaraldehyde crosslinked controls were examined in vitro for degree of crosslinking, resistance to degradation by collagenase, and material property changes. Likewise treated menisci were implanted in rats for eight weeks and examined for calcium content and biomechanical changes. TGA treatment for three days significantly reduced collagen loss by 88% and increased thermal denaturation temperatures (Ts) above 80 degrees C versus Ts of 70 degrees C or less for non-crosslinked meniscus. In vitro, TGA and TGA-MABP significantly increased aggregate modulus by 19% and 32% compared to native controls, respectively. TGA decreased permeability by 53% while TGA-MABP increased it by 303%. In vivo, TGA significantly reduced explant calcification by 42% compared to glutaraldehyde, and including MABP reduced it by 90%. Analyses revealed that TGA and TGA-MABP stabilized menisci had significantly lower modulus and permeability values than glutaraldehyde controls by at least 28% and 86%, respectively. It is concluded that TGA crosslinking of meniscus increases resistance to both collagenase degradation and pathologic calcification, while demonstrating comparable or improved biomechanical properties versus glutaraldehyde controls.
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PMID:Biomechanical and biologic effects of meniscus stabilization using triglycidyl amine. 1955 90

Aortic valve (AoV) stenosis is the third most common cardiovascular disease. The pathogenesis of AoV stenosis is associated with an inflammatory process where MMPs serve important roles. The aim of the present study was to determine the association between matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and inflammatory factors, and AoV stenosis at various degrees of severity compared with the control. A total of 18 patients with mild, 19 with moderate and 15 with severe AoV stenosis were included in the present stud, and 50 individuals were enrolled in the control group. The severity of stenosis was determined by echocardiography. The expression levels of chemerin, fibroblast growth factor 21, MMP-1, -3, and -9, and TIMP-1 and -3 were analyzed by ELISA. Data were analyzed using GraphPad Prism7 software. The expression levels of MMP-1 was increased in patients with stenosis compared with the control group (P=0.0043). Distribution of the trimodal MMP-1 values was obtained in the stenosis group and monomodal in the control group. A total of 80% of patients in the stenosis group presented significantly increased expression levels of MMP-1 compared with the control group (P=0.0002). Expression of MMP-1 was significantly higher in all stenosis groups compared with the control. The highest expression level of MMP-1 appeared in patients with moderate stenosis (P<0.0001). There was no significant difference in the expression of MMP-3, MMP-9 and TIMP-1 in the aortic stenosis group, compared with the control group. A positive correlation between MMP-1 and MMP-9 expression levels was identified (r=0.37; P=0.017). The increase of MMP-1 was correlated with the increase of MMP-9, but not with the level of MMP-3. The expression levels of chemerin was significantly elevated in patients with stenosis compared with healthy patients. The highest expression levels of chemerin were determined in patients with mild (P=0.0001) and moderate (P=0.0007) stenosis and decreased with the grade of severity compared with the control group. The expression of FGF-21 was significantly different between the control and mild (P=0.013), moderate (P=0.015) and severe stenosis (P=0.003) groups. The expression levels of FGF-21 increased with the increase in severity grade, reaching the maximum for severe stenosis. The results of the present study indicated that the inflammatory process is predominantly occurring at the early, mild stage of stenosis and the most prominent extracellular matrix remodeling occurs in moderate stenosis (demonstrated by MMP-1 levels). In patients with severe stenosis, the levels of MMP-1 and chemerin (which are lower than in a case of mild or moderate stenosis) could indicate the development of calcinosis and the reduction in activity or inactivation of the inflammatory process.
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PMID:Impact of several proinflammatory and cell degradation factors in patients with aortic valve stenosis. 3090 30