| Project/Area Number |
17209058
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MORITA Ikuo Tokyo Medical and Dental University, Graduate School, Professor (60100129)
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| Co-Investigator(Kenkyū-buntansha) |
AKIYASHI Kazunari Tokyo Medical and Dental University, Institute of Biomaterials and Bioengineering, Professor (90201285)
NAKAHAMA Ken-ichi Tokyo Medical and Dental University, Graduate School, Associate Professor (60281515)
ICHINOSE Shizuko Instrumental Analysis Research Center, 機器分析センター, Assistant Professor (60014156)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥50,180,000 (Direct Cost: ¥38,600,000、Indirect Cost: ¥11,580,000)
Fiscal Year 2007: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2006: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2005: ¥31,070,000 (Direct Cost: ¥23,900,000、Indirect Cost: ¥7,170,000)
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| Keywords | Connexin / Gap Junction / Differentiation / Cell Density / Expression / mRNA Stability / PI3 kinase / 発現調節 / mRNA安定性 / 骨代謝 / DDS / 細胞増殖 |
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| Research Abstract |
Cx43 plays various roles in cell proliferation, differentiation, and apoptosis. To ascertain whether Cx43 contributes to cell differentiation, we initially characterized Cx43 expression during cell differentiation. The present study shows that in hepatocytes, Cx43 expression is upregulated with carcinogenesis, and vitamin K2 attenuated cancer cell proliferation and stimulated cell differentiation by the suppression of Cx43 expression, and Cx43 is crucial for RPE cell differentiation in vitro. Cx43 short hairpin RNA dramatically inhibited RPE cell differentiation, whereas Cx43 overexpression facilitated it. Furthermore, the regulation of RPE cell differentiation by Cx43 results from the accumulation of cAMP, not from intercellular gap junctional communication (GJIC). In addition to membrane trafficking of connexin (Cx) protein, we focused on the regulation of gene expression of Cx43. The enhanced expression of Cx43 with high cell density was independent of gap functional intracellular c
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ommunication and gap junction between cells. However, the membrane trafficking of cx43 was affected with the gap junction between cells. The expression of Cx43 upregulated by high density was abolished by SP1 binding motif in Cx43 promoter region and Sp3 down-regulation will contribute the upregulation of cx43 gene expreswsion. Moreover, the Cx43 gene expression was also regulated by mRNA stabilization. Both PI3 kinase and AKT affected mRNA stabilization of Cx43. We also examined the expression pattern of various connexins and the role of Cx in cell differentiation. We have established the cell differentiation systems; isolation of multi potent stem cells from periodontal ligament tissues and differentiation to osteoblasts, endothelial cell differentiation from cord blood and differentiation of retina pigmental epithelia cells. It is interesting that Cx43 expression was upregulated by cell differentiation in all systems examined and Cx43 involves in cell differentiation via gap junction-independent manner. Less
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