The purpose of this study is to define the mechanism of decrease in osteoblastic activity at the cellular level, which is principally responsible for the slow, age-related phase of bone loss. Our central hypothesis is that age-related impairment in the production of key growth factors in the bone microenvironment is responsible for most or all of the impaired osteoblast function. We have developed state-of-the-art methods for isolating human trabecular osteoblasts in cancellous bone and for measuring the small concentration of mRNA for the relevant growth factors. In the proposed studies, we will compare steady-state levels of mRNA for the relevant growth factors. In the proposed studies, we will compare steady-state levels of mRNA for IGF-I, IGF-II, TGFB, and bFGF in osteoblasts from a group of young normal adult women with those from a group of elderly normal women to test our hypothesis.
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