No abstract

Tendon harvest causes significant weakness of hamstring muscle strength at high knee flexion angles, but such weakness can be minimized if the gracilis tendon is preserved.

Susceptibility to osteoarthritis, the most common human arthritis, is known to be influenced by genetic factors. Through a genome-wide association study using approximately 100,000 SNPs, we have identified a previously unknown gene on chromosome 3p24.3, DVWA, which is associated with susceptibility to knee osteoarthritis. Expressed specifically in cartilage, DVWA encodes a 276-amino-acid protein with two regions corresponding to the von Willebrand factor type A domain (VWA domain). Several DVWA SNPs are significantly associated with knee osteoarthritis in two independent Japanese case-control cohorts. This association was replicated in a Japanese population cohort and a Han Chinese case-control cohort (combined P = 7.3 x 10(-11)). DVWA protein binds to beta-tubulin, and the binding is influenced by two highly associated missense SNPs (rs11718863 and rs7639618) located in the VWA domain. The Tyr169-Cys260 isoform of DVWA, which is overrepresented in knee osteoarthritis, showed weaker interaction. Our findings reveal a new paradigm for study of osteoarthritis etiology and pathogenesis.

Cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a secreted protein expressed by chondrocytes; the expression is repressed by interleukin 1␤ (IL-1␤). To investigate the transcriptional mechanism, by which CD-RAP expression is suppressed by IL-1␤, deletion constructs of the mouse CD-RAP promoter were transfected into rat chondrocytes treated with or without IL-1␤. The results revealed an IL-1␤-responsive element located between ؊2138 and ؊2068 bp. As this element contains a CAAT/enhancer-binding protein (C/EBP) motif, the function of C/EBP␤ and C/EBP␦ was examined. IL-1␤ stimulated the expression of C/EBP␤ and -␦, and the direct binding of C/EBP␤ to the C/EBP motif was confirmed. The ؊2251-bp CD-RAP promoter activity was down-regulated by co-transfection with C/EBP expression vectors. Mutation of the C/EBP motif abolished the inhibitory response to IL-1␤. Additionally, C/EBP expression vectors were found to down-regulate the construct containing the promoter and enhancer of the type II collagen gene. Finally, the enhancer factor, Sox9, was shown to bind adjacent to the C/EBP site competing with C/EBP binding. Taken together, these results suggest that C/EBP␤ and -␦ may play an important role in the IL-1␤-induced repression of cartilage-specific proteins and that expression of matrix proteins will be influenced by the availability of positive and negative trans-acting factors.