| RRC ID |
30664
|
| 著者 |
Mise-Omata S, Alles N, Fukazawa T, Aoki K, Ohya K, Jimi E, Obata Y, Doi T.
|
| タイトル |
NF-κB RELA-deficient bone marrow macrophages fail to support bone formation and to maintain the hematopoietic niche after lethal irradiation and stem cell transplantation.
|
| ジャーナル |
Int Immunol
|
| Abstract |
Bone remodeling and hematopoiesis are interrelated and bone marrow (BM) macrophages are considered to be important for both bone remodeling and maintenance of the hematopoietic niche. We found that NF-κB Rela-deficient chimeric mice, generated by transplanting Rela (-/-) fetal liver cells into lethally irradiated hosts, developed severe osteopenia, reduced lymphopoiesis and enhanced mobilization of hematopoietic stem and progenitor cells when BM cells were completely substituted by Rela-deficient cells. Rela (-/-) hematopoietic stem cells from fetal liver had normal hematopoietic ability, but those harvested from the BM of osteopenic Rela (-/-) chimeric mice had reduced repopulation ability, indicating impairment of the microenvironment for the hematopoietic niche. Osteopenia in Rela (-/-) chimeric mice was due to reduced bone formation, even though osteoblasts differentiated from host cells. This finding indicates impaired functional coupling between osteoblasts and hematopoietic stem cell-derived cells. Rela-deficient BM macrophages exhibited an aberrant inflammatory phenotype, and transplantation with wild-type F4/80(+) BM macrophages recovered bone formation and ameliorated lymphopoiesis in Rela (-/-) chimeric mice. Therefore, RELA in F4/80(+) macrophages is important both for bone homeostasis and for maintaining the hematopoietic niche after lethal irradiation and hematopoietic stem cell transplantation.
|
| 巻・号 |
26(11)
|
| ページ |
607-18
|
| 公開日 |
2014-11-1
|
| DOI |
10.1093/intimm/dxu062
|
| PII |
dxu062
|
| PMID |
24908679
|
| MeSH |
Animals
Bone Diseases, Metabolic / genetics
Bone Diseases, Metabolic / metabolism
Bone Diseases, Metabolic / pathology
Bone Marrow / metabolism
Bone Marrow / pathology
Hematopoiesis / genetics*
Hematopoietic Stem Cell Transplantation
Lymphopoiesis / genetics
Macrophages / metabolism*
Male
Mice
Mice, Knockout
Osteoclasts / metabolism
Osteogenesis / genetics*
Stem Cell Niche / genetics*
Transcription Factor RelA / deficiency*
Transcription Factor RelA / genetics
Transplantation Chimera
Whole-Body Irradiation
|
| IF |
3.519
|
| 引用数 |
8
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC00144 |
