Role of NF-kB RelA in homeostasis of bone and hematopoietic niche
| Project/Area Number |
22591073
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | The Institute of Physical and Chemical Research |
|---|
Principal Investigator |
MISE Setsuko 独立行政法人理化学研究所, 生体情報統合技術開発チーム, 開発研究員 (00269052)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
DOI Satoru 独立行政法人理化学研究所, 生体情報統合技術開発チーム, サブチームリーダー (60227684)
|
|---|
| Project Period (FY) |
2010 – 2012
|
| Project Status |
Completed (Fiscal Year 2012)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
|
|---|
| Keywords | 骨代謝 / 造血幹細胞ニッチ / NF-kB / 骨髄マクロファージ / マクロファージ / プロスタグランジンE2 / 血球分化 / 転写因子 / 造血幹細胞 / 骨芽細胞 / 破骨細胞 |
|---|
| Research Abstract |
Bone remodeling and hematopoiesis are interrelated. We found that NF-κB rela-deficient chimeric mice, generated by transplanting rela^<-/-> fetal liver cells into lethally irradiated hosts, develop osteopenia. Rela^<-/-> HSCs from fetal liver have normal hematopoietic ability, but those harvested from the bone marrow of osteopenic rela^<-/-> chimeric mice have reduced repopulation ability, indicating impairment of microenvironment for hematopoietic niche. Osteopenia in rela^<-/-> chimeric mice is due to reduced bone formation, even though osteoblasts differentiate from host mesenchymal stem cells. This finding indicates impaired interaction between osteoblasts and HSC-derived cells. Transplantation with wild-type F4/80^+ bone marrow macrophages recovers bone formation in rela^<-/-> chimeric mice and ameliorates lymphopoiesis, indicating that rela^<-/-> macrophages fail to support bone formation and hematopoietic niche. Therefore, RelA in F4/80^+ macrophages is important both for bone homeostasis and for maintaining the hematopoietic niche after lethal irradiation and HSC transplantation.
|
Report
(4 results)
Research Products
(11 results)
