Research in my laboratory falls under the umbrella of gene expression and regulation in the musculoskeletal system. The first area of research involves the regulation of fracture repair by growth factors. We have focused on the roles of TGF-?'s and FGF's. Current work has identified several sequences for cognate TGF-? receptors. These sequences are currently being extended, and ligands for the putative receptors identified. The second area of research activity focuses on the molecular and cellular events responsible for bone resorption around failed total joint implants. Our work in this area evaluates regulation of matrix metalloproteinase gene expression by macrophages. The third area of interest evaluates the cellular mechanisms by which musculoskeletal tissues respond to mechanical stress. We are using ultrasound to mechanically stimulate cultured cells; current work is evaluating the frequency response of cells to ultrasound signals. Finally, we are interested in the molecular mechanisms that confer drug resistance in chondrosarcomas. We have identified the expression of MDR1, MRP, and a novel related gene in surgical sarcoma samples. The regulation of these genes in chondrosarcomas and their role in conferring drug resistances is being examined.