Abstract
Aggrecanase-mediated aggrecan degradation is a significant event in early-stage osteoarthritis (OA). Aggrecanases belonging to the 'A Disintegrin And Metalloproteinase with ThromboSpondin motifs' (ADAMTS) family of proteinases play a significant role in aggrecan depletion in osteoarthritic cartilage. There has been considerable interest in the possible role of these aggrecanases, especially ADAMTS-4 and ADAMTS-5, as therapeutic targets in OA. This article discusses recent data regarding ADAMTS-4 and ADAMTS-5 in OA, with emphasis on the relationship between aggrecanase and aggrecan degradation as well as the role of aggrecanase in OA.
MeSH terms
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ADAM Proteins / antagonists & inhibitors
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ADAM Proteins / metabolism*
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ADAMTS4 Protein
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ADAMTS5 Protein
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Aggrecans / metabolism*
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Extracellular Matrix / enzymology
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Humans
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Osteoarthritis / enzymology*
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Procollagen N-Endopeptidase / antagonists & inhibitors
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Procollagen N-Endopeptidase / metabolism*
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Tissue Inhibitor of Metalloproteinase-3 / metabolism
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Tissue Inhibitor of Metalloproteinase-3 / pharmacology
Substances
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ACAN protein, human
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Aggrecans
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TIMP3 protein, human
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Tissue Inhibitor of Metalloproteinase-3
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ADAM Proteins
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ADAMTS5 Protein
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ADAMTS5 protein, human
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Procollagen N-Endopeptidase
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ADAMTS4 Protein
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ADAMTS4 protein, human