| Project/Area Number |
14370708
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Periodontal dentistry
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
MUKOHYAMA Hitoshi Tokyo Medical and Dental University, Graduate school, Senior Lecturer, 大学院・医歯学総合研究科, 講師 (00242214)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KASUGAI Shohei Tokyo Medical and Dental University, Graduate school, Professor, 大学院・医歯学総合研究科, 教授 (70161049)
AOKI Kazuhiro Tokyo Medical and Dental University, Graduate school, Senior Lecturer, 大学院・医歯学総合研究科, 講師 (40272603)
NITTA Hiroshi Tokyo Medical and Dental University, Graduate school, Associate Professor, 大学院・医歯学総合研究科, 助教授 (70237767)
NAGASAWA Toshiyuki Tokyo Medical and Dental University, Graduate school, Research Associate, 大学院・医歯学総合研究科, 助手 (90262203)
谷口 尚 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (90171850)
尾澤 昌悟 東京医科歯科大学, 歯学部附属病院, 講師 (50323720)
|
|---|
| Project Period (FY) |
2002 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2004: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥5,900,000 (Direct Cost: ¥5,900,000)
|
|---|
| Keywords | Neuropeptide / vasoactive intestinal peptide / osteoclasts / ostebolasts / VIP receptor / vasoactive intestinal peptide / neuropeptiede / vasoactive intesitinal peptide |
|---|
| Research Abstract |
In the present study, we examined the effect of VIP on osteoclast formation in mouse bone marrow cultures. In this culture system, 1,25(OH)_2-vitamin D3 (D3) or parathyroid hormone (PTH) induce formation of multinucleated cells positive for tartrate resistant acid phophatase (TRAP+MNC), with calcitonin binding sites and an ability to form pits on bone slices ; three phenotypic expressions of osteoclasts. VIP reduced, in a concentration-dependent manner, osteoclast formation, the number of binding sites for radiolabelled calcitonin and the amounts of resorption pits in cultures stimulated by PTH or D3. Osteoclast formation stimulated by D3 was associated with stimulations of mRNA for calcitonin receptor, cathepsin K and TRAP. The stimulatory direct by D3 on calcitonin receptor and cathepsin K mRNA, but not that on TRAP mRNA, was down regulated by VIP. VIP increased the mRNA for the osteoblastic markers alkaline phosphatase and osteopontin. The inhibition of TRAP+MNC formation by VIP was mimicked by forskolin. The presence of VIP during last two days of a 7-day-culture period was sufficient to inhibit osteoclast formation. Not only VIP, but also PACAP-38 and secretin, but not glucagon, inhibited osteoclast formation and the number of calcitonin binding sites in D3 stimulated cultures. RT-PCR revealed the expression of VIP-1 and VIP-2 receptor subtypes with the VIP-2 receptor mRNA down regulated by D3. These findings indicate that VIP, via VIP-1 and/or VIP-2 receptors, inhibits osteoclastogenesis by a cyclic AMP-dependent mechanism, due to an inhibitory effect at the late stage of osteoclastogenesis. The present study supports the idea of a neuro-osteogenic interaction in bone metabolism.
|
