Grant-in-Aid for Scientific Research (S)
|Allocation Type||Single-year Grants|
Morphological basic dentistry
|Research Institution||Tokyo Medical and Dental University(2004-2006)|
YAMAGUCHI Akira Tokyo Medical and Dental University, Graduate School, Oral Pathology, Professor, 大学院医歯学総合研究科, 教授 (00142430)
KATSUBE Ken-ichi Tokyo Medical and Dental University, Graduate School, Oral Pathology, Assistant Professor, 大学院医歯学総合研究科, 講師 (20233760)
SAKAMOTO Kei Tokyo Medical and Dental University, Graduate School, Oral Pathology, Research Associate, 大学院医歯学総合研究科, 助手 (00302886)
TAMAMURA Sadahiro Tokyo Medical and Dental University, Graduate School, Oral Pathology, Research Associate, 大学院医歯学総合研究科, 特任助手 (70431963)
柴田 恭明 長崎大学, 大学院医歯薬学総合研究科, 助手 (80253673)
塚崎 智雄 長崎大学, 大学院・医歯薬学総合研究科, 助教授 (50315230)
藤田 修一 長崎大学, 大学院・医歯薬学総合研究科, 助手 (00181355)
進藤 裕幸 長崎大学, 大学院・医歯薬学総合研究科, 教授 (30107677)
原 宜興 長崎大学, 大学院・医歯薬学総合研究科, 教授 (60159100)
|Project Period (FY)
2002 – 2006
Completed(Fiscal Year 2006)
|Budget Amount *help
¥113,230,000 (Direct Cost : ¥87,100,000、Indirect Cost : ¥26,130,000)
Fiscal Year 2006 : ¥22,360,000 (Direct Cost : ¥17,200,000、Indirect Cost : ¥5,160,000)
Fiscal Year 2005 : ¥22,360,000 (Direct Cost : ¥17,200,000、Indirect Cost : ¥5,160,000)
Fiscal Year 2004 : ¥22,360,000 (Direct Cost : ¥17,200,000、Indirect Cost : ¥5,160,000)
Fiscal Year 2003 : ¥22,360,000 (Direct Cost : ¥17,200,000、Indirect Cost : ¥5,160,000)
Fiscal Year 2002 : ¥23,790,000 (Direct Cost : ¥18,300,000、Indirect Cost : ¥5,490,000)
|Keywords||osteoblast / Runx2 / CCN3 / Notch / Mesenchymal stem cell / frog / evolution / bone regeneration / 骨形成 / BMP / アフリカツメガエル / 軟骨内骨化 / 再生 / 再生療法 / 細胞分化 / 両生類|
We investigate the following issues in this research. 1)Analyses of regulatory factors of osteoblast differentiation, 2)Establishment and characterization of mesenchymal stem cells, 3)Evolutional changes of skeletal tissues. Results in this study is as follow.
1)Analyses of regulatory factors of osteoblast differentiation
a)We established runx2-deficient cell lines, and demonstrate that osteoblast differentiation is induced by BMP-2 in these cells by using other transcription factors such as Dlx5 and Msx2. b)CCN3 (NOV) inhibits osteoblast differentiation by interacting with BMP and Notch signaling pathways. c)We revealed the important role of Msx2 in osteoblast differentiation.
2)Establishment and characterization of mesenchymal stem cells
a)We established mesenchymal stem cells from human hamartoma, and characterized their differentiation potencies into various mesenchymal cells, b)We established multipotent mesenchymal cell lines form human osteosarcoma cell lines, which exhibited differ
entiation potential into osteoblasts, chondrocytes, and adipocytes, c)We investigated the differentiation potential of multipotent KUSA cells, which were isolated from murine bone marrow, and revealed that CCN3 inhibits osteoblast differentiation in this cell line.
3)Evolutional changes of skeletal tissues
a)We demonstrated that endochondral ossification is delayed prominently in frog long bones, compared with that in mammals. This was caused by the different expression profiles of Banded Hedgehog in frog, compared with expression profiles of Indian Hedgehog in mouse long bones. b)We established cell culture methods for muscle and chondrocytes isolated frogs. c)We compared the bone regeneration process between frog and mouse. Bone regeneration process was extremely delayed, compared with that of mouse. d)We investigated whether bones in frogs play important role in calcium reservoir, and suggested that the bones in frogs will not be involved in calcium reservoir.
These results will provide important information to establish new therapies for bone regeneration and osteoporosis. Less