| Budget Amount *help |
¥109,460,000 (Direct Cost: ¥84,200,000、Indirect Cost: ¥25,260,000)
Fiscal Year 2010: ¥21,450,000 (Direct Cost: ¥16,500,000、Indirect Cost: ¥4,950,000)
Fiscal Year 2009: ¥21,970,000 (Direct Cost: ¥16,900,000、Indirect Cost: ¥5,070,000)
Fiscal Year 2008: ¥21,710,000 (Direct Cost: ¥16,700,000、Indirect Cost: ¥5,010,000)
Fiscal Year 2007: ¥21,190,000 (Direct Cost: ¥16,300,000、Indirect Cost: ¥4,890,000)
Fiscal Year 2006: ¥23,140,000 (Direct Cost: ¥17,800,000、Indirect Cost: ¥5,340,000)
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| Research Abstract |
To understand the mechanism of boneformation factors that are involved in the regulation and pathology, we have been examining molecular bases with respect to the micro environment. We identified that and CIZ is involved in the regulations ob bone information by altering the signaling of osteoblasts. CIZ and ECM proteins are regulating cell attachment and transcription. BMP is a most critical cytokine for bone information and implicated in niche regulation. Niche for bone cells and the regulation of cells in such location has not been well elucidated. As interaction of local and systemic hormone is important for coordinate regulation of bone formation we focused on parathyroid hormone (PTH). Such systemic hormonal control exerts its effect through the regulation of local target tissues, which in turn regulate upstream signals in a feedback loop. Parathyroid hormone receptor (PPR) transgenic mice expressing a constitutively active form of the receptor (caPPR) specifically in cells of th
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e osteoblast lineage have a high bone mass phenotype. In these mice, OPN deficiency further increased bone mass. Bone formation was also found to be controlled by ANA and Cnot7 that inhibit BMP. Epigentic link and PTH dependent regulation by M-CSF and MCP is also found to be important. Regeneration of bone requires the combination of appropriate drugs and an appropriate delivery system to control cell behavior. However, the delivery of multiple drugs to heal bone is complicated by the availability of carriers. The aim of this study was to explore a new system for delivery of a selective EP4 receptor agonist (EP4A) in combination with low-dose bone morphogenetic protein 2 (BMP-2). Combination treatment with EP4A and low-dose BMP-2 in nanogel efficiently activated bone cells to regenerate calvarial bone by forming both outer and inner cortical plates as well as bone marrow tissue to regenerate a structure similar to that of intact calvaria. EP4A enhanced low-dose BMP-2-induced cell differentiation and activation of transcription events in osteoblasts. These data indicate that combined delivery of EP4A and low-dose BMP-2 via nanogel-based hydrogel provides a new system for bone repair. Less
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