The proposed study aims to elucidate the role of growth factors in the onset of age-related osteoporosis. In bone marrow stromal (BMS) cell cultures, osteoprogenitor cells appear in fibroblast colony formation units (CFU-F) and express alkaline phosphatase. In rodents, the bone forming potential of the osteoblasts is in direct proportion to the number of alkaline phosphatase (ALP) positive CFU-F. In the proposed study, young (4 month) and old (24 month) C57BL/6J mice will be used as donors of BMS cells. These mice have lowCFU-F forminf ability, thin bones and low circulating insulin-like growth factor I (IGF-1) levels. BMS cells from young and old mice will be assayed and compared in the following manner: 1) ALP activity in CFU-F; 2) Mitogenic response to individual growth factors known to be important in bone homeostasis including IGF-1, PDGF-AA, TGFbeta-1, bFGF and BMP-7 (OP-1), and combination mitogenic influence of IGF-1 and the growth factor that is most mitogenic in individual assays; 3. endogenous expression of IGF-1 and chosen growth factor that gives greatest mitogenic response. Results from these experiments will further our understanding of how growth factors act and interact to affect young and aged osteoprogenitor cells and whether defects in these activities play a role in lowering of the response to IGF-1 in aged osteoblasts.
