This research proposal suggests a novel approach to the study of the effects of 1) intermittent cyclic deformation, 2) a known bone growth factor (insulin-like growth factor 1, IGF-1), and 3) synergistic effects of #1 and #2 on resultant in vitro bone matrix (osteoid) deposition and mineralization by two populations of cells: a) differentiating (populations containing preosteoblasts: days 1-9 of culture), and b) differentiated osteoblasts (days 11-21 of culture). The effect of cyclic deformation on resultant in vitro deposition and mineralization of osteoid by either cell population is unknown, as previous studies have been performed in either a static or a continuous loading environment. The following experiments are designed to test the following hypotheses: 1) exposure of both differentiating and differentiated osteogenic cell populations to IGF-1 or cyclic deformation increases the resultant osteoid deposition and mineralization, and 2) there is a significant synergistic effect between cyclic deformation and IGF-1 on osteoid deposition and mineralization by each cell population. To test these hypotheses, osteogenic cells will be isolated and grown for 21 days in vitro. At either 1-9 (differentiating populations) or 11-21 (differentiated populations) days, cells will be exposed to either various a) concentrations of IGF-1 b) frequencies and intensity of cyclic deformation, or c) combinations of 'a' and 'b'. The surface area and percentages of mineralized and unmineralized osteoid will be calculated by histomorphometric techniques. Mean deposition of each substance will be compared by factorial analysis of variance to determine the effects of IGF-1, the frequency and magnitude of cyclic deformation, and the interactive effects of each parameter on mineralized and unmineralized osteoid deposition by each population of cells. These results will provide important new data concerning the individual and combined effects of mechanical forces and growth factors on bone matrix (osteoid) deposition and mineralization and may provide a method for producing a more favorable healing environment for bone fractures.
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