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)

The collagenolytic enzyme systems in the human, normal, and prolapsed intervertebral discs have been studied. Normal discs obtained postmortem contained a novel collagenase with specificity toward Type II collagen and gelatin but with little or no activity against Type I collagen. A method whereby enzymes are detected quantitatively in extracts of human tissue using specific substrates, without prior chromatographic separation of the enzymes, has been developed and used to study 14 normal discs and 35 surgically excised prolapsed discs. No differences were observed between annulus and nucleus extracts of normal discs either in the pattern of enzymes or the quantity. The intermediate zone between nucleus and annulus was excised and was not tested. Highly significant differences were observed between the enzyme patterns of the normal and prolapsed discs. The major collagenolytic activity of normal discs is against Type II collagen and 1 alpha 2 alpha 3 alpha collagen, there is little activity toward Type I collagen and virtually none toward elastin. Conversely, the prolapsed disc is more highly active against the substrates elastin and Type I collagen than against Type II collagen or 1 alpha 2 alpha 3 alpha collagen. The individual patterns of enzymes of the 35 prolapsed discs were virtually identical. Similarly there was little internal variation between the patterns of enzymes extracted from discs, obtained postmortem, which were apparently normal. The striking difference between the normal and prolapsed disc could be an important factor in the pathogenesis of disc prolapse.
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PMID:Abnormal connective tissue degrading enzyme patterns in prolapsed intervertebral discs. 378 41

Animal experimental studies are reported in which the enzyme collagenase was used to digest the nucleus pulposus of the intervertebral disc in both dogs and monkeys. Studies in the same animals indicated a low risk toxicity. Clinical studies were started in 1979, in which the results in 82 patients are reported. All patients were subjected to rigid standards of selection. Of 78 patients followed, 80.4% had good results, 4.9% fair results, and 14.7% had poor results. There were no instances of toxicity. A double-blind study of 30 patients indicates clearcut superiority of collagenase over placebo in relieving the symptoms of herniated disc.
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PMID:Intervertebral discolysis with collagenase. 629 14

The molecular and morphologic features of herniated human intervertebral disc tissues are of particular importance to clarify the pathogenesis. The present study analyzed the biochemical and morphological features of herniated intervertebral disc tissues to determine the constituent factors responsible for intervertebral disc herniation. A total of 32 herniated disc specimens and 4 control disc samples were analyzed. Collagen subunit composition, collagenase activity, lipid peroxidation level, caspase-3 activity, metal levels, morphologic studies, and genetic analysis were performed on herniated disc tissues of chronic (group A) and acute (group B) group and compared with findings of control group. Nick translation analysis in situ revealed apoptotic-positive stained DNA fragments as black-brown spots in herniated disc tissues. The presence of type II collagen in control disc samples and its absence in herniated samples were confirmed immunohistochemically. The increased caspase-3 activity, the apoptotic-positive stained DNA fragments, and the electron microscopic findings suggest enhanced programmed cell death in herniated discs. The significant increase in lipid peroxidation levels and collagenase activity, and the low metal levels suggest the enhancement of cell death signals in herniated discs, caused by oxygen stress. Linkage analysis of herniated disc tissues in Japanese individuals may suggest ethnic variation. These findings may be helpful in understanding the pathogenesis of herniated disc disease.
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PMID:Biochemical and morphological changes in herniated human intervertebral disc. 1179 73

The aim of this study was to identify the possible correlation between polymorphisms in matrix metalloproteinase (MMP)-1 and MMP-3 and their corresponding protein levels in disc tissues obtained from patients with lumbar disc herniation (LDH) using biochemical and immunohistochemical analyses. Blood and disc samples were obtained from 100 patients with LDH who underwent a lumbar microdiscectomy. Based on the radiological degeneration, the patients were diagnosed with grade 2, 3, or 4 LDH. MMP-1 -1607 1G/2G and MMP-3 -1171 5A/6A were analyzed by real-time polymerase chain reaction. The expressions of MMP-1 and MMP- 3 were detected by biochemical and immunohistochemical analyses. We found no association between the MMP-1 polymorphism and disc degeneration and MMP-1 expression. However, patients expressing the 6A/6A and 5A/6A alleles of MMP-3 -11715A/6A showed higher MMP-3 expression, compared to those expressing the 5A/5A genotype. Additionally, the radiological degeneration grades were correlated with the histological degeneration scoring. Protein levels and immunopositive cell rates of MMP-1 and MMP-3 were associated with disc degeneration grades. Moreover, the MMP-1 and MMP-3 expression and the histological and radiological scores were positively correlated and the MMP-3 -11715A/6A polymorphism was associated with MMP-3 expression in herniated disc tissues. This study is the first to investigate polymorphisms in MMP-1 and MMP-3, as well as their corresponding protein expressions. We also quantified an association between the radiological degeneration grades and MMP-1 and MMP- 3 expression. Further genomic studies on MMPs could focus on the utilization of MMP-1 and MMP-3 as markers for the prevention and treatment of this disease.
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PMID:Effects of MMP-1 and MMP-3 gene polymorphisms on gene expression and protein level in lumbar disc herniation. 2770 15

Back pain is the second leading cause of disability among American adults and is currently treated either with conservative therapy or interventional pain procedures. However, the question that remains is whether we, as physicians, have adequate therapeutic options to offer to the patients who suffer from chronic low back pain but fail both conservative therapy and interventional pain procedures before they consider surgical options such as discectomy, disc arthroplasty, or spinal fusion. The purpose of this article is to review the potential novel therapies that are on the horizon for the treatment of chronic low back pain. We discuss medications that are currently in use through different phases of clinical trials (I-III) for the treatment of low back pain. In this review, we discuss revisiting the concept of chemonucleolysis using chymopapain, as the first drug in an intradiscal injection to reduce herniated disc size, and newer intradiscal therapies, including collagenase, chondroitinase, matrix metalloproteinases, and ethanol gel. We also review an intravenous glial cell-derived neurotrophic growth factor called artemin, which may repair sensory nerves compressed by herniated discs. Another new drug in development for low back pain without radiculopathy is a subcutaneous monoclonal antibody acting as nerve growth factor called tanezumab. Finally, we discuss how platelet-rich plasma and stem cells are being studied for the treatment of low back pain. We believe that with these new therapeutic options, we can bridge the current gap between conservative/interventional procedures and surgeries in patients with chronic back pain.
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PMID:Treatment of chronic low back pain - new approaches on the horizon. 2854 69