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rdf:type | |
lifeskim:mentions | |
pubmed:dateCreated |
1995-5-4
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pubmed:abstractText |
We have compared the effects of a general matrix metalloproteinase (MMP) inhibitor (CT435) with those of a concentration-dependent specific gelatinase inhibitor (CT543; Ki < 20 nM) on bone resorption in vitro. The test systems consisted of measuring: (i) the release of 45Ca2+ from prelabelled mouse calvarial explants; (ii) the release of 45Ca2+ from prelabelled osteoid-free calvarial explants co-cultured with purified chicken osteoclasts; and (iii) lacunar resorption by isolated rat osteoclasts cultured on ivory slices. Both CT435 and CT543 dose-dependently inhibited the release of 45Ca2+ from neonatal calvarial bones stimulated by either parathyroid hormone or 1,25-dihydroxyvitamin D3. Moreover, CT543 produced a 40% inhibition at a concentration (10(-8) M) selective for the inhibition of human gelatinases A and B. CT435 (10(-5) M) and CT543 (10(-5) M) partially inhibited the release of 45Ca2+ from osteoid-free calvarial explants by chicken osteoclasts with a maximum of approximately 25% for unstimulated cultures, and approximately 36% for cultures stimulated by interleukin-1 alpha (IL-1 alpha; 10(-10) M). Neither inhibitor prevented lacunar resorption on ivory by unstimulated rat osteoclasts, but the compounds produced a partial reduction in both the number and total surface area of lacunae in IL-1 alpha-stimulated cultures, with maximal action at 10(-5) M. Neither of the inhibitors affected protein or DNA synthesis, nor the IL-1 alpha-stimulated secretion of the lysosomal enzyme beta-glucuronidase. Immunocytochemistry demonstrated that isolated rabbit osteoclasts constitutively expressed gelatinase A and synthesized gelatinase B, collagenase and stromelysin, as well as the tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) following IL-1 alpha stimulation. These experiments have shown that in addition to collagenase, gelatinases A and B are likely to play a significant role in bone resorption. They further suggest that MMPs produced by osteoclasts are released into the sub-osteoclastic resorption zone where they participate in bone collagen degradation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Gelatinases,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Phenethylamines,
http://linkedlifedata.com/resource/pubmed/chemical/Tissue Inhibitor of...
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9533
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
107 ( Pt 11)
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3055-64
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:7699005-Animals,
pubmed-meshheading:7699005-Bone Resorption,
pubmed-meshheading:7699005-Cells, Cultured,
pubmed-meshheading:7699005-Chickens,
pubmed-meshheading:7699005-Gelatinases,
pubmed-meshheading:7699005-Glycoproteins,
pubmed-meshheading:7699005-Immunohistochemistry,
pubmed-meshheading:7699005-Metalloendopeptidases,
pubmed-meshheading:7699005-Mice,
pubmed-meshheading:7699005-Morpholines,
pubmed-meshheading:7699005-Osteoclasts,
pubmed-meshheading:7699005-Phenethylamines,
pubmed-meshheading:7699005-Rats,
pubmed-meshheading:7699005-Rats, Wistar,
pubmed-meshheading:7699005-Tissue Inhibitor of Metalloproteinases
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pubmed:year |
1994
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pubmed:articleTitle |
The effects of selective inhibitors of matrix metalloproteinases (MMPs) on bone resorption and the identification of MMPs and TIMP-1 in isolated osteoclasts.
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pubmed:affiliation |
Cell and Molecular Biology Department, Strangeways Research Laboratory, Worts Causeway, Cambridge, UK.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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