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)

Drugs in the tetracycline family can inhibit mammalian tissue collagenase both in vitro and in vivo by a mechanism that is independent of antibiotic action. The epiphyseal cartilages of rachitic rats contain extremely high levels of collagenase (CGase), and we have used this model to study further the phenomenon of tetracycline inhibition of tissue CGase. Rickets was induced in rats by phosphate/vitamin D deficiency and parameters of gross bone morphology, bone chemistry, and serum chemistry were evaluated in both rachitic and nonrachitic animals with and without treatment with oral tetracyclines (TETs). Minocycline (or doxycycline) partially suppressed the appearance of many of the expected changes in the rachitic animals, including gross bone hardness, growth plate widening, long bone length, suppression of weight gain, and decreased bone ash content. The effects were dose dependent and were associated with marked suppression of the enhanced CGase activity. Examination of collagen breakdown products by SDS-PAGE documented that the rachitic enzyme behaved like other mammalian collagenases including in vitro inhibition with minocycline 10-20 micrograms/ml and with a nonantibiotic tetracycline. No evidence of TET osseous toxicity was noted, and, in fact, administration of TET to nonrachitic animals had a mildly favorable effect on growth and development. TET suppression of CGase can be demonstrated in a well defined model system and this form of pharmacologic enzyme inhibition can be a useful probe for delineating the role of the enzyme in connective tissue pathology.
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PMID:Inhibition of epiphyseal cartilage collagenase by tetracyclines in low phosphate rickets in rats. 284 40

Skeletal problems are common in both young and old poultry and are often related to bone weakness. They affect mortality on the farm and condemnations within processing plant and thus raise both welfare and economic concerns. To understand the basis of bone strength, the metaphyseal histology, composition, and the biomechanical properties of tibiae from 7- and 72-wk-old male and female broiler breeder chickens were compared. The biochemical constituents included ash, collagen, proteoglycan, transforming growth factor-beta (TGF-beta), pyridinium crosslinks, and the organic matrix-associated fluorescence. Blood variables were measured to determine the metabolic status of these birds as related to bone physiology. Although there were no differences in blood chemistry of 7-wk-old males and females, there were several differences between young and old birds. The levels of calcium, triglyceride, and iron were higher in older females than in older males. The collagen content was reduced, and the proteoglycan content increased in 72-wk-old hens. The TGF-beta content of bones from 7-wk-old females was higher than that of other groups of birds. Bone strength and stiffness, measured using loads at break and Young's modulus, respectively, were higher in older birds. The presence of medullary bones in 72-wk-old hens did not affect their bone strength, although it reduced strain values and increased Young's modulus. Compared to other groups, the 72-wk-old hens had a higher content of an inorganic matrix. The levels of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) and the collagenase-extractable fluorescence of the organic matrix from older birds was higher. The decalcified bone matrix from older birds also showed higher susceptibility to bacterial collagenase than their younger counterparts. Bone strength showed positive correlations with its ash content, density, pyridinium crosslinks, and the fluorescence of the matrix. However, the correlation was strong with both pyridinium crosslinks and the fluorescence of the organic matrix. These results suggest that bone strength is influenced by the content of its collagen crosslinks.
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PMID:Comparative differences in the composition and biomechanical properties of tibiae of seven- and seventy-two-week-old male and female broiler breeder chickens. 1047 52