| Project/Area Number |
15K15548
|
|---|
| Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Orthopaedic surgery
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
Kitoh Hiroshi 名古屋大学, 医学系研究科, 准教授 (40291174)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
杉浦 洋 名古屋大学, 医学部附属病院, 医員 (40750477)
松下 雅樹 名古屋大学, 医学部附属病院, 病院助教 (60721115)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
|
|---|
| Keywords | 進行性骨化性線維異形成症 / ドラッグ・リポジショニング / 異所性骨化 / Id1 / ALK2 / ドラッグスクリーニング / 薬効スクリーニング |
|---|
| Outline of Final Research Achievements |
Fibrodysplasia ossificans progressiva (FOP) is a severely disabling heritable disorder of connective tissue characterized by progressive heterotopic ossification in various extraskeletal sites. FOP is caused by a gain-of-function mutation in ALK2, which causes up regulation of a transcriptional factor, Id1. We screened FDA-approval drugs for suppression of the Id1 promoter activated by the mutant ALK2 in C2C12 myogenic cells. We found that azelastine HCl (anti-histamine), Fluvastatin sodium salt (ant-hyperlipidemia), and Trimipramine maleate salt (anti-depressant) suppressed the Id1 promoter activity in a dose-dependent manner. These drugs also downregulated the expressions of the Id1-target osteoblastic genes such as alkaline phosphatase and osteocalcin.
|
