2012 Fiscal Year Final Research Report
Role of NF-kB RelA in homeostasis of bone and hematopoietic niche
| Project/Area Number |
22591073
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | The Institute of Physical and Chemical Research |
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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)
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| 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)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 骨代謝 / 造血幹細胞ニッチ / NF-kB / 骨髄マクロファージ |
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| 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.
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