PROGRAM PROJECT GRANT

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DESCRIPTION (provided by applicant): The underlying primary hypothesis of the Program project is that intervertebral disc degeneration contributes to low back pain and a second hypothesis is that the process of degeneration can be prevented, retarded or repaired. Our premise is that both biological and biomechanical factors contribute to the pathogenesis of disc degeneration. The Program project therefore, addresses both the biomechanical and biological aspects of disc degeneration. By improving our understanding of the degenerative process and by exploring different approaches to diagnose, prevent, retard or repair the degenerative process, we will ultimately decrease the problem of low back pain in society. The approach taken in this Program project is to address (1) diagnostic techniques by which the impact of the degenerative changes can be assessed in vivo; (2) mechanical factors contributing to the development of degenerative disc changes; (3) biochemical changes occurring with disc degeneration and; (4) methods to slow, reverse or repair the degenerative process. The Program project will be completed using a multi-disciplinary approach with the participation of members from orthopedic surgery, radiology, biomechanics, anatomy, biochemistry, and molecular biology. Project I will study in vivo segmental spine motion of the lumbar spine in normal volunteers and discogenic low-back-pain patients. Project 2 will look at the relationship between disc injury and repetitive loading using finite element models with experimental validation. Project 3 will determine how changes in disc structure and composition correlate with changes in the metabolism of cells from the NP and AF and will use culture models in vitro to study degenerative processes and the ability of specific growth factors to promote repair. Project 4 will study regeneration of the intervertebral disc matrix by assessing the effects of growth factors and gene gun mediated gene transfer of growth factors to intervertebral disc cells. At the end of the program period we will have: (1) New diagnostic techniques to better assess clinically the mechanical consequences of disc degeneration on the intervertebral disc. (2) An improved understanding of the effects of repetitive loading on the mechanical integrity of the intervertebral disc, and this information can be used to identify appropriate subjects for treatment. (3) Knowledge about the relationship between disc degeneration and changes in the metabolism of the extracellular matrix of the intervertebral disc as well as alterations in the expression of specific genes by disc cells. This will provide a platform for biochemical or molecular therapeutic approaches for intervertebral disc degeneration. (4) Knowledge about alternative approaches to prevent, retard or repair disc degeneration based on the degree of degeneration. Each of the projects are highly integrated with each other and supported by Biomechanics, Biochemistry and Administrative Cores.