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. (7th June 2014)

• Record Type: Journal Article
• Authors: Mise-Omata, Setsuko; Alles, Neil; Fukazawa, Taro; Aoki, Kazuhiro; Ohya, Keiichi; Jimi, Eijiro; Obata, Yuichi; Doi, Takahiro
• Is Part Of: International immunology. Volume 26:Number 11(2014:Nov.)
• Page Start: 607
• Page End: 618
• Publication Date: 2014-06-07
• Subjects: bone remodeling -- hematopoietic niche -- macrophage -- NF-κB -- osteoimmunology; Immunology -- Periodicals; 616.079
• DOI: 10.1093/intimm/dxu062
• Languages: English
• ISSNs: 0953-8178

Abstract

Abstract : Bone marrow macrophages are required for bone homeostasis and the hematopoietic niche 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.