Abstract: The invention discloses that members of a subfamily of receptor tyrosine kinases comprising TYRO3, Axl, cMer and ligands thereof, such as GAS6 are suitable targets for the development of new therapeutics to treat, prevent or ameliorate OA. The invention also relates to methods to treat and/or ameliorate OA and pharmaceutical compositions therefore comprising modulators with inhibitory effect on the expression or activity of members of this subfamily of receptor tyrosine and related ligands. The invention also relates to a method to identify compounds with therapeutic usefulness to treat OA, comprising identifying compounds that can, e.g., inhibit activity and/or expression of these polypeptides.

Abstract: High-throughput functional screening assays are provided that identify genes and gene products that are associated with the pathogenesis of osteoarthritis (OA) in chondrocytes. In addition, genes and gene products identified by such functional assays are also provided. The genes and gene products provided herein are useful inter alia for diagnosing OA in individuals and as drug targets for identifying drugs to treat OA.

Abstract: The invention discloses PI3K, PKB, IL-1, and OSM as suitable targets for the development of new therapeutics to treat, prevent or ameliorate osteoarthritis (OA). The invention relates to methods to treat, prevent or ameliorate OA and pharmaceutical compositions therefor comprising substances with inhibitory effects on PI3K and/or PKB enzyme activity and/or gene expression and IL-1 and/or OSM activity or gene expression. The invention also relates to a method to identify compounds with therapeutic usefulness to treat OA, comprising identifying compounds that can effect PI3K and/or PKB activity and/or gene expression and/or IL-1 or OSM activation of PI3K and/or PKB activity and/or gene expression which leads to downregulation of AGG-1 and/or COL-3 and thus prevent, treat or ameliorate OA in vivo.