title: [Asporin, a susceptibility gene for osteoarthritis].
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.
authors.affiliation: Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN.
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000483:Alleles; D001224:Aspartic Acid / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D010003:Osteoarthritis / Q000235:genetics*; D011110:Polymorphism, Genetic; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: C439889:ASPN protein, human; D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D001224:Aspartic Acid