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[Asporin, a susceptibility gene for osteoarthritis]
1Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN.
Abstract:
Osteoarthritis (OA) is the most common form of human arthritis. Genetic factors have been implicated in OA. Through a candidate gene-association study, we found association between asporin and OA. Asporin is an extracellular matrix component expressed abundantly in the articular cartilage of OA patients. A significant association between a polymorphism in the aspartic acid (D) repeat of the asporin gene (ASPN) and knee OA was found; the D14 allele of ASPN is over-represented relative to the common D13 allele, and its frequency increases with disease severity. The D14 allele is also over-represented in patients with hip OA. The association of asporin is replicated in European population by meta-analysis. Asporin suppresses transforming growth factor-beta (TGF-beta)-mediated expression of aggrecan and type II collagen genes and reduced proteoglycan accumulation in an in vitro model of chondrogenesis. Asporin co-localized to and bound to TGF-beta, and inhibited TGF-beta-Smad signal. Clarification of molecular pathway of OA relating to asporin and TGF-beta would lead to order-made medicine and novel therapeutic strategies for OA.
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