MOLECULAR BASIS OF GROWTH FACTOR ENHANCED TENDON REPAIR

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The focus of this research proposal is to define the growth factor and matrix gene expression changes in early tendon injury. It will also evaluate pharmaceutical means of enhancing the healing response to achieve tendon repair tissue that more closely resembles the mechanical properties of normal tendon. The ultimate goal is healed tendons that are less likely to sustain reinjury. Our specific aims include documentation of the temporal and spatial expression of collagen types I and III, the growth factors insulin-like growth factor I (IGF-I) and transforming growth factor beta (TGF-beta), and the IGF binding proteins during the healing response of flexor tendon following collagenase injury in the horse. The relationship between growth factor expression and subsequent changes in collagen expression are of central interest. This information will provide the scientific basis for decisions regarding selection, timing, and duration of administration of biologicals in this and future investigations. Previous in vitro studies document the beneficial effects of IGF-I on tendon healing and the in vitro study outlined in this proposal will provide preliminary data on beta-aminopriopionitrile (BAPN). The information from these in vitro studies will be combined with that from the temporal healing study to perform the two in vivo studies outlined, one using IGF-I alone and the other using a combination of IGF-I and BAPN. Tissues will be analyzed by histologic stains, in situ hybridization, immunostaining, autoradiography, and biochemical assays for DNA content and matrix composition. Statistical analyses will be performed as dictated by the specific study design, including paired t-tests, one-way analysis of variance, Tukey's post hoc comparisons, individual regression analysis, and Pearsons's Correlation. Significance will be set at p less than or equal to 0.05.