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Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis
DC Field | Value | Language |
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dc.contributor.author | Echtermeyer, Frank | - |
dc.contributor.author | Bertrand, Jessica | - |
dc.contributor.author | Dreier, Rita | - |
dc.contributor.author | Meinecke, Ingmar | - |
dc.contributor.author | Fuerst, Martin | - |
dc.contributor.author | Song, Yeong Wook | - |
dc.contributor.author | Theilmeier, Gregor | - |
dc.contributor.author | Pap, Thomas | - |
dc.contributor.author | Herzog, Christine | - |
dc.contributor.author | Lee, Yun Jong | - |
dc.contributor.author | Neugebauer, Katja | - |
dc.date.accessioned | 2012-05-24T04:15:08Z | - |
dc.date.available | 2012-05-24T04:15:08Z | - |
dc.date.issued | 2009-09 | - |
dc.identifier.citation | NATURE MEDICINE; Vol.15 9; 1072-U127 | ko_KR |
dc.identifier.issn | 1078-8956 | - |
dc.identifier.uri | https://hdl.handle.net/10371/76392 | - |
dc.description.abstract | Aggrecan cleavage by a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 5 (ADAMTS-5) is crucial for the breakdown of cartilage matrix during osteoarthritis(1,2), a degenerative joint disease that leads to the progressive destruction of articular structures. The mechanisms of ADAMTS-5 activation and their links to the pathogenesis of osteoarthritis remain poorly understood, but syndecans have been shown to be involved in the activation of ADAMTS-4 (ref. 3). Here we show that syndecan-4 is specifically induced in type X collagen-producing chondrocytes both in human osteoarthritis and in murine models of the disease. The loss of syndecan-4 in genetically modified mice and intra-articular injections of syndecan-4-specific antibodies into wild-type mice protect from proteoglycan loss and thereby prevent osteoarthritic cartilage damage in a surgically induced model of osteoarthritis. The occurrence of less severe osteoarthritis-like cartilage destruction in both syndecan-4-deficient mice and syndecan-4-specific antibody-treated wild-type mice results from a marked decrease in ADAMTS-5 activity. Syndecan-4 controls the activation of ADAMTS-5 through direct interaction with the protease and through regulating mitogen-activated protein kinase (MAPK)-dependent synthesis of matrix metalloproteinase-3 (MMP-3). Our data suggest that strategies aimed at the inhibition of syndecan-4 will be of great value for the treatment of cartilage damage in osteoarthritis. | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | NATURE PUBLISHING GROUP | ko_KR |
dc.title | Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis | ko_KR |
dc.type | Article | ko_KR |
dc.contributor.AlternativeAuthor | 이윤종 | - |
dc.contributor.AlternativeAuthor | 송영욱 | - |
dc.identifier.doi | 10.1038/nm.1998 | - |
dc.citation.journaltitle | NATURE MEDICINE | - |
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dc.description.tc | 43 | - |
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