The dysfunction of macrophages/osteoclast precursors in bone metabolism after transplantation with RelA-deficient HSC.

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462392
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University (2015); Institute of Physical and Chemical Research (2013)
• Principal Investigator: Mise-Omata Setsuko 東京医科歯科大学, 医歯(薬)学総合研究科, 非常勤講師 (00269052)
• Co-Investigator(Kenkyū-buntansha): Doi S. Takahiro 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, 研究員 (60227684)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 骨芽細胞 / 造血幹細胞移植 / マクロファージ / 炎症

Outline of Final Research Achievements

Lethal radiation of mice before HSC transplantation induces eradication of hematopoietic cells, but its effect on osteogenic cells may be less considered. The mice transferred with RelA-deficient fetal liver cells developed severe osteoporosis, and even the mice transferred with wild type cells reduced trabecular bones, suggesting that lethal radiation may damage to osteogenic cells. In contrast to wound healing M2 type macrophages reducing in bone marrow of the mice transferred with RelA-deficient HSCs, inflammatory M1 type macrophages were aberrantly activated. Co-transplantation of wild type macrophages have recovered osteoporosis which occurs in the mice transferred with RelA-deficient fetal liver cells, indicating that the dysfunction of RelA-deficient macrophages cause the uncoupling of bone metabolism.

Free Research Field

骨代謝