Investigation of bone resorption by osteoclasts : aiming at therapy regulating osteoclastic bone resorption.
| Project/Area Number |
20590321
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | Himeji Dokkyo University |
|---|
Principal Investigator |
TOHYAMA Yumi Himeji Dokkyo University, 薬学部, 教授 (70362770)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
梶本 武利 姫路獨協大学, 薬学部, 講師 (00509953)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
KAJI Hiroaki 姫路獨協大学, 薬学部, 講師 (10368706)
TANAKA Chisato 姫路獨協大学, 薬学部, 助手 (30461122)
|
|---|
| Project Period (FY) |
2008 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | 破骨細胞 / リソソーム / ATP / P2X7 / Syk / Rab27a / 核酸受容体 / アセチル化 / 細胞骨格 / チロシンキナーゼ |
|---|
| Research Abstract |
Osteoclasts are bone-degrading cells playing an exclusive role in bone remodeling but molecular mechanism of osteolysis is poorly understood. Here we established a traceable and reproducible in vitro analyzing system for osteolysis using human osteoclasts because we found that an energy molecule ATP acts as a specific osteolysis initiator via P2X7-nucleotide receptor. We further show that deacetylation of α-tubulin is a critical reaction for osteolysis. Pharmacological inhibition of α-tubulin deacetylation resulted in defective bone resorption, accompanied by (1) failure of sealing-zone formation and (2) ceased secretion of osteolytic granules. Furthermore, kinetics of deacetylation was found to be regulated by Syk. These data suggest a novel P2X7-Syk-acetylation/deacetylation pathway for therapeutic targets in osteolytic diseases.
|
Report
(4 results)
Research Products
(21 results)
