1998 Fiscal Year Final Research Report Summary
Development of bone metabolism improvement medicines based on the analysis of signal transduction
| Project/Area Number |
08557101
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 展開研究 |
|---|
| Research Field |
Functional basic dentistry
|
|---|
| Research Institution | Showa University |
|---|
Principal Investigator |
SUDA Tasuo Showa University, School of Dentistry, Professor, 歯学部, 教授 (90014034)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KUDO Ichiro Showa University, School of Pharacy, Professor, 薬学部, 教授 (30134612)
AKIYAMA Shuichi Showa University, School of Dentistry, Assistant, 歯学部, 助手 (70276591)
UDAGAWA Nobuyuki Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (70245801)
JIMI Eijiro Showa University, School of Dentistry, Assistant, 歯学部, 助手 (40276598)
TAKAHASHI Naoyuki Showa University, School of Dentistry, Associate Professor, 歯学部, 助教授 (90119222)
|
|---|
| Project Period (FY) |
1996 – 1998
|
| Keywords | osteoblast / osteoclast / myoblast / BMP / Smad / Estrogen / IL-7 / ODF |
|---|
| Research Abstract |
1. Regulatory mechanism of osteoblast differentiation was studied using 02012 myoblasts treated with BMP-2. BMP-2 induced Qsteoblastic differentiation of 02012 cells through BMP receptor (BM PR) IA.Samd 1 and Smad 5 were shown to be involved in the signaling pathway of BMPR IA.
2. Estrogen deficiency in mice caused by ovariectomy (OVX) results in marked bone loss and accumulation of pre-B cells in bone marrow. Treatment of mice with IL-7 which stimulates B-lymphopoiesis induced marked bone loss. IL-7 receptor knockout mice exhibited increased bone volume. These results suggest that accumulation of pre-B cells is involved in the stimulated bone resorption in OVX mice.
3. Expression of mRNAs of estrogen receptor (ER) a and b was studied in various tissues in rats. EAb mRNA was highly expressed in osteoblasts. This suggests that estrogen action on bone is mediated by ERb.
4. Osteoblasts express osteoclast differentiation factor (ODF) as a membrane associated factor. A cDNA encoding ODF was isolated from a cDNA library of ST2 cells. ODF was a new member of the TNF-ligand family. Osteoblasts expressed ODF in response to osteotropic factors. A soluble form of ODF (sODF) together with M-0SF stimulated osteoclast formation from spleen cells in the absence of osteoblasts.
5. A new culture system for human osteoclastogenesis was established. When human peripheral blood mononuclear cells were cultured with sODF and M-CSF, human osteoclasts were formed within 7 days.
6. Osteoblasts induce pit forming activity of osteoclasts placed on dentine slices. sODE also stimulated pit-forming activity of osteoclasts in the absence of osteoblasts. Activation of NF-kB by ODF appeared to be involved in the induction of osteoclast function.
|
