Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis

摘要: The degenerative joint disease osteoarthritis is known to involve the activation of protease ADAMTS-5. Now, Frank Echtermeyer and his colleagues have shown that transmembrane proteoglycan syndecan-4 responsible for this activation. They also show genetic deletion syndecan-4, or inhibition with a blocking antibody, reduces progression in mouse model. Aggrecan cleavage by disintegrin metalloproteinase thrombospondin type 1 motif, member 5 (ADAMTS-5) crucial breakdown cartilage matrix during osteoarthritis1,2, leads progressive destruction articular structures. mechanisms ADAMTS-5 their links pathogenesis remain poorly understood, but syndecans been be involved ADAMTS-4 (ref. 3). Here we specifically induced X collagen–producing chondrocytes both human murine models disease. loss genetically modified mice intra-articular injections syndecan-4–specific antibodies into wild-type protect from thereby prevent osteoarthritic damage surgically model osteoarthritis. occurrence less severe osteoarthritis-like syndecan-4–deficient antibody–treated results marked decrease activity. Syndecan-4 controls through direct interaction regulating mitogen-activated protein kinase (MAPK)-dependent synthesis metalloproteinase-3 (MMP-3). Our data suggest strategies aimed at will great value treatment