A large focus of our research endeavors is in the area of skeletal tissue regeneration after fracture. These projects cover a diverse set of basic studies that are directed at uncovering the underlying molecular mechanisms that promote fracture healing, as well as pre-clinical trials of biological compounds and small molecule pharmaceuticals that might have either positive or negative effects on bone repair. Basic science studies on fracture healing include two large project areas examining the role of the innate immune system as a primary initiator in bone regeneration and have primarily focused on the roles of tumor necrosis factor (TNF) and bone morphogenetic protein (BMP) function during fracture healing. Our pre-clinical trials have focused on the basic development of both BMP and parathyroid hormone (PTH) as therapeutics for bone healing as well as the roles of NSAIDS and coxibs as inhibitors of bone repair. Our projects cover a full range of research approaches from whole animal studies using transgenic models to cell biology experiments using cultured marrow stromal stem cells, primary sources of osteoblasts and osteoclasts, and transgenic cell lines. We use a combination of state-of-the-art assessment tools to examine fracture healing including microcomputer assisted tomography (CT), biomechanical testing for strength and material property assessment and novel tools of three dimensional tissue reconstruction of sequential histological specimens. These studies also make use of all forms of molecular analyses of mRNA expression from RT-PCR to large scale transcriptional profiling.