Description): The osteoblast is the bone-forming cell and there is a growing body of clinical evidence that functional defects of the osteoblast can be at the origin of osteoporosis. This observation underlines the importance of understanding the molecular mechanisms of osteoblast differentiation and function. To address this question, the investigators have cloned and characterized the first transcriptional activator of osteoblast differentiation termed Osf2/Cbfal. Osf2/Cbfal controls osteoblast differentiation during development but also the expression of several structural genes expressed in osteoblasts. The hypothesis is that Osf2/Cbfal is required in postnatal life to maintain the osteoblast phenotype. To test the multiple functions of Osf2/Cbfal during development and after birth, they propose: -to perform an extensive study of Osf2/Cbfal pattern of expression during development and after birth as well as a study of other molecular markers involved during skeletogenesis in wild-type and Cbfal-deficient mice; -to analyze the differentiation ability of Osf2/Cbfal in cell culture and in vivo; -to inhibit or abrogate Osf2/Cbfal function in differentiated osteoblasts in vivo; and -to overexpress Osf2/Cbfal in osteoblasts in vivo and determine if this overexpression leads to an increase in bone formation.
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