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KAKEN_16K09867seika.pdf
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放射線照射による骨髄内環境の損傷とマクロファージによる修復機構の解析
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ホウシャセン ショウシャ ニ ヨル コツズイナイ カンキョウ ノ ソンショウ ト マクロファージ ニ ヨル シュウフク キコウ ノ カイセキ
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Hōshasen shōsha ni yoru kotsuzuinai kankyō no sonshō to makurofāji ni yoru shūfuku kikō no kaiseki
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Repairing of hematopoietic niche in bone marrow after X-ray irradiation
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三瀬, 節子
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ミセ, セツコ
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Mise, Setsuko
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慶應義塾大学・医学部 (信濃町) ・特任助教
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Research team head
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科研費研究者番号 : 00269052
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青木, 和広
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アオキ, カズヒロ
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Aoki, Kazuhiro
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東京医科歯科大学・大学院医歯学総合研究科・教授
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Research team member
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科研費研究者番号 : 40272603
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2019
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科学研究費補助金研究成果報告書
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2018
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本研究では、致死量のX線照射後に造血幹細胞移植を行うと骨量が減少するマウスと増加するマウスの2つの異なる系統のマウスを用いて、骨量の維持や造血能力は、骨髄内の脂肪細胞の分化の程度に影響されることを明らかにした。骨量の減少するRelA欠損型マウスでは、骨髄内に多くの脂肪細胞が分化すると共に造血能が低下し末梢に多くの造血細胞が流出する。反対に骨量が増加するSpred1/Spred2欠損型マウスは、分化した脂肪細胞が速やかに除去され、造血能力がよくなる。脂肪細胞が増えるRelA欠損型マウスでは炎症を引き起こすマクロファージが多く存在していることがわかった。
Lethal X-ray radiation before HSC transplantation often induce the bone loss in the patients. We found a correlation between bone loss and the impairment of hematopoietic environment induced by hyper-differentiation of adipocytes, by using two different strains of mice, one is RelA-deficient mouse suffering from severe bone loss and the other is Spred1/Spred2 double knockout mouse which increases its bone mass after HSC transplantation. The adipocytes differentiated in the bone morrow after X-ray radiation were rapidly deprived in the Spred DKO mice and in these mice hematopoietic ability was enhanced compared with wild type mice. In contrast, the number of adipocytes markedly increased and hematopoietic ability was impaired in RelA-deficient mice. Inflammatory macrophages are highly differentiated in RelA-deficient mice, it may cause the over-differentiation of adipocytes.
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研究種目 : 基盤研究 (C) (一般)
研究期間 : 2016~2018
課題番号 : 16K09867
研究分野 : 造血幹細胞移植
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