| Budget Amount *help |
¥16,470,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2007: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2006: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2005: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Research Abstract |
We previously identified a bone specific transcription factor Osterix (Osx) that appeared to be an essential regulator of osteoblast differentiation along with another key transcription factor Runx2/Cbfa1, although the mechanisms of the regulation for osteoblast differentiation and the skeletogenesis have not been clarified in detail so far. We thus hypothesized the existence of the transcription factor network that would orchestrate the developmental machinery of those processes, and to understand the reality of the hypothesis, we investigated putative factors involved in the network. The factors include Runx2, Cnot7, Schumurri-2 and Ciz which were supposed to contribute to the Osterix-related regulatory pathways. By analyzing null-mutant mice deficient for these factors, we revealed molecular involvement of each factor for cell signaling and bone formation through their actions on osteoblasts in various way. In these studies, we mainly focused on the pathways stimulated by humoral factors that activates osteoblast function, including bone morphogenetic proteins (BMPs) and parathyroid hormone (PTH). In addition, we investigated novel aspects of osteoblastic differentiation, through mechanisms of molecular pathways related to transcription factors JunD and NfatC1, or by patterning signal molecule PlexinD1, a cation-channel Trpv4, and rennin-angiotensin system (RAS) using gene targeting disruption of the experimental mice. Although the entire picture of the transcription factor network is still unveiled, our study indicated possible involvement of multiple factors in the machinery, clarification of which would be beneficial for developing application methods for related clinical situations.
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