| In vitro inhibition of aggrecanase activity by tetracyclines and proteoglycan loss from osteoarthritic human articular cartilage. | |
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MedLine Citation:
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PMID: 20069635 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Tetracyclines were reported to slow down the progression of cartilage damage both in an animal model of osteoarthritis (OA) and in humans. In search for the underlying mechanisms we examined whether tetracyclines possess an inhibitory potential on the activity of aggrecanases and inflammatory mediators and can thus prevent proteoglycan (PG) loss from human articular cartilage. In vitro activity of aggrecanase-1 and -2 was recorded in the presence of 1-100 microM tetracycline, minocycline, or doxycyline. Human knee articular cartilage explants were sorted according to the degree of OA and treated for 10 days with tetracycline derivatives in the presence of interleukin-1 (IL-1beta). Synthesis and loss of PGs, nitric oxide (NO), and prostaglandin E(2) (PGE(2)), as well as the viability were determined. Tetracyclines derivatives dose-dependently inhibited the activities of both aggrecanases in vitro, whereas no inhibitory effect of tetracyclines on any proteoglycanolytic activities within IL-1beta-treated human cartilage explants were found. Tetracyclines can significantly modulate NO and PGE(2) levels, but have no effect on PG synthesis and loss within the same human cartilage explant cultures. Altogether, our data show that tetracyclines have no inhibitory potential on any proteoglycanolytic activities within mild or moderately affected human OA cartilage at therapeutic achievable plasma levels. |
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Authors:
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J?rgen Steinmeyer; Jens Kordelle; Henning St?rz |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of orthopaedic research : official publication of the Orthopaedic Research Society Volume: 28 ISSN: 1554-527X ISO Abbreviation: J. Orthop. Res. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-04-21 Completed Date: 2010-05-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8404726 Medline TA: J Orthop Res Country: United States |
Other Details:
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Languages: eng Pagination: 828-33 Citation Subset: IM |
Copyright Information:
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(c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. |
Affiliation:
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Department of Orthopaedic Surgery, University Hospital Giessen and Marburg GmbH, Giessen, Germany. juergen.steinmeyer@ortho.med.uni-giessen.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ADAM Proteins
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antagonists & inhibitors* Aged Cartilage, Articular / metabolism* Cells, Cultured Chondrocytes / cytology, drug effects Dinoprostone / biosynthesis Humans Middle Aged Nitric Oxide / biosynthesis Osteoarthritis / drug therapy*, metabolism Procollagen N-Endopeptidase / antagonists & inhibitors* Protease Inhibitors / pharmacology* Proteoglycans / metabolism* Tetracyclines / pharmacology*, therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Protease Inhibitors; 0/Proteoglycans; 0/Tetracyclines; 10102-43-9/Nitric Oxide; 363-24-6/Dinoprostone; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/ADAMTS5 protein, human; EC 3.4.24.-/aggrecanase-1; EC 3.4.24.14/Procollagen N-Endopeptidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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