| Project/Area Number |
11307041
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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 | Osaka University |
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Principal Investigator |
YONEDA Toshiyuki Osaka University Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (80142313)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Riko Osaka University Graduate School of Dentistry, Associate Professor, 大学院・歯学研究科, 助教授 (60294112)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥37,750,000 (Direct Cost: ¥36,100,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2001: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2000: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1999: ¥24,200,000 (Direct Cost: ¥24,200,000)
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| Keywords | Osteoclast / Osteoblast / Adipocytes / NF-kB / JNK / BMP2 / Cbfa1 / Smad / Src / アデノウイルス / Csk |
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| Research Abstract |
(1) Role of C/EBP beta in the differentiation of mesenchymal stem cells into osteoblasts and adipocytes
We found that C/EBP beta is able to induce the differentiation of mesenchymal stem cells into not only adipocytes but also osteoblasts. In addition, an isoform of C/EBP beta, LIP, blocks the adipogenesis in a dominant-negative fashion, but exhibits osteogenic action as a co-factor for Cbfa1. Our data provide the new insight into the understanding the molecular mechanisms that determine the direction of mesenchymal stem cells in bone.
(2) The role of JNK/c-Jun signaling in osteoclast differentiation
Treatment of RANK ligand (RANKL) promoted the osteoclastic differentiation of mouse monocytic cell line RAW264 cells. RANKL also activated JNK, c-Jun and transcription of AP-1. Overexpression of dominant negative JNK or c-Jun markedly inhibited the formation of osteoclasts by RANKL stimulation in RAW264 cells by blocking the activation of JNK or c-Jun signaling. The data suggest the crucial role of JNK/c-Jun signaling in the osteoclast differentiation by RANKL.
(3) Suppressive effects on osteoblastic differentiation and Induction of its apoptosis by TNF-alpha
We observed that TNF suppressed the osteoblastic differentiation of mesenchymal stem cells and promoted the apoptosis of mature osteoblasts. Blockade of NF-kB signaling by overexpression of mutant l-kB alpha profoundly inhibited the effect of TNF on osteoblastic differentiation of undifferentiated mesenchymal cells. In contrast, overexpression of the mutant l-kB alpha accelerated the apoptosis induced by TNF. The data suggest that TNF suppresses osteoblastic differentiation of mesenchymal cells and accelerated the apoptosis by regulating NF-kB signaling.
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