Arthritis is characterized by the breakdown of extracellular matrix compounds and subsequent loss of articular cartilage. The destruction of the extracellular matrix of articular cartilage and bone in arthritic joints is thought to be mediated by excessive proteolytic activity. We recently identified zinc-metalloproteinases ADAMTS-7 and ADAMTS-12 (ADAMTS: A Disintegrin And Metalloproteinase with ThromboSpondin motifs) as the new cartilage-degrading enzymes using functional genetic screen. My first research focus is to investigate the roles of ASADTS proteins in arthritis, with the goal of understanding the degradative events that occur in patients with arthritic disorders. We thus hope to increase our ability to monitor the biological and physical properties of cartilage extracellular matrix as they become altered by various disease processes, and ultimately to develop effective therapeutic strategies for arthritis, such as blocking enzymatic agents by isolating and utilizing their naturally occurring inhibitors and/or analogous compounds. The differentiation of uncommitted mesenchymal cells into osteoblasts is a fundamental molecular event governing both embryonic development and repair of bone. Osteogenesis is tightly controlled by a variety of molecules that might regulate BMP-2/Smads/CBFA1 pathway in both positive and negative fashions. Our findings have implicated p204, an interferon-inducible protein, as another critical regulator in these processes. My second research focus is to investigate the roles of p204 in skeletal development, with the goal of understanding the molecular events involved and of providing a biological basis for designing therapeutic approaches to such musculoskeletal disorders as osteoporosis and osteopetrosis.