| Project/Area Number |
24592821
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Functional basic dentistry
|
|---|
| Research Institution | Matsumoto Dental University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NINOMIYA Tadashi 松本歯科大学, 総合歯科医学研究所, 講師 (00360222)
TAKAHASHI Naoyuki 松本歯科大学, 総合歯科医学研究所, 教授 (90119222)
|
|---|
| Research Collaborator |
KADOTA Shigetoshi
KIKUCHI Takanobu
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | 破骨細胞 / 転写因子 / NFATc1 / リン酸化 / 骨吸収 / 天然化合物 / 質量分析 |
|---|
| Outline of Final Research Achievements |
Arctigenin was previously shown to inhibit osteoclastogenesis; however, this inhibitory mechanism has yet to be elucidated. In this study, we showed that arctigenin inhibited the action of NFATc1 by novel mechanism. Arctigenin strongly inhibited RANKL-induced osteoclast formation in mouse bone marrow macrophage (BMM) cultures, in which the calcineurin-dependent NFATc1 pathway was activated. Arctigenin, but not cyclosporin A suppressed osteoclast formation in co-cultures of osteoblastic cells and bone marrow cells, in which the osteoblastic cell-dependent NFATc1 pathway was activated. ChIP analysis confirmed that arctigenin inhibited the recruitment of NFATc1 to the promoter region of the NFATc1 target gene. These results suggest that arctigenin induces a dominant negative species of NFATc1, which inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways.
|
