DTIC ADA456020: Gene Therapy for Fracture Repair pdf

DTIC ADA456020: Gene Therapy for Fracture Repair

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Effective gene therapy for musculoskeletal injuries requires the optimization of the components and techniques for the accurate assessment of therapeutic benefits. We have identified a murine leukemia virus (MLV) vector that provides robust transgene expression in fracture tissues, and applied it to the rat femur fracture model to express therapeutic transgenes. With these techniques, the MLV vector has been used to simultaneously express engineered bone morphogenetic protein (BMP)-4 and fibroblast growth factor (FGF)-2 transgenes in the healing fracture. Initial results indicate that this combination of FGF-2 proliferative and BMP-4 osteogenic functions does indeed enhance fracture repair. To characterize the molecular pathways of fracture healing, we have used microarray technology to examine normally healing fracture tissues during the inflammatory and endochondral bone formation stages of fracture repair. Inflammatory gene expression, so important to the initiation of healing, has been described. Molecular pathways have been characterized that 1) could mediate the regeneration of healing bone, and 2) involve intracellular FGF regulation of fracture repair.

Independent techniques have confirmed microarray-based identification of genes expressed in fracture repair. Unknown genes expressed in fracture repair have been identified and the effects of inhibiting their expression in bone cell lines in vitro are under investigation

• Creator/s: Defense Technical Information Center
• Date: 12/1/2005
• Year: 2005
• Book Topics/Themes: DTIC Archive, Lau, William, LOMA LINDA VETERANS ASSOCIATION FOR RESEARCH AND EDUCATION CA, *REPAIR, *GENES, *WOUNDS AND INJURIES, *GROWTH(PHYSIOLOGY), *MUSCULOSKELETAL SYSTEM, *REGENERATION(PHYSIOLOGY), *BONE FRACTURES, CONTROL, TISSUES(BIOLOGY), OPTIMIZATION, BENEFITS, HEALING, GENE THERAPY, CARTILAGE, MORPHOGENESIS, LEUKEMIA, BONES, ANATOMICAL MODELS, LEGS, INFLAMMATION, VIRUSES, FIBROBLASTS, THERAPY, RATS, PROTEINS, ACCURACY

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