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KAKEN_23592231seika.pdf
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Title |
転写抑制因子Blimp1によるエピジェネティック制御を介した破骨細胞分化制御機構
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テンシャ ヨクセイ インシ Blimp1 ニ ヨル エピジェネティック セイギョ オ カイシタ ハコツ サイボウ ブンカ セイギョ キコウ
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Tensha yokusei inshi Blimp1 ni yoru epijenetikku seigyo o kaishita hakotsu saibo bunka seigyo kiko
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Regulation of osteoclastogenesis by transcriptional repressor Blimp1 via epigenetic regulation
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宮内, 芳輝
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ミヤウチ, ヨシテル
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Miyauchi, Yoshiteru
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慶應義塾大学・医学部・共同研究員
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Research team head
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科研費研究者番号 : 90445411
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2014
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科学研究費補助金研究成果報告書
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2013
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破骨細胞は骨吸収能を有する生体唯一の細胞であることから、その制御は骨粗鬆症等の治療標的となり得る。我々は転写抑制因子であるB lymphocyte induced maturation protein 1 (Blimp1)が破骨細胞分化促進に必須であること、また、Blimp1欠損マウスは胎生致死であるが、アダルトにおいてCre/loxP systemによりBlimp1を欠損させた場合は、致死的な副作用は認めず、破骨細胞分化の著しい抑制と骨量の増大を認めた。このことから、Blimp1はアダルトにおいて骨量減少性疾患の良い治療標的となり得ることが明らかとなった(J Biol Chem 2012)。
Osteoclasts are unique bone resorbing cells, and thus are therapeutic targets to treat bone diseases such as osteoporosis. We found that B lymphocyte induced maturation protein 1 (Blimp1), a transcriptional repressor, was required for osteoclastogenesis. Although Blimp1-null mutant mice are embryonic lethal, Blimp1 conditional knockout at an adult stage by a Cre/loxP system did not promote lethal adverse effects in mice, while resulted in significant inhibition of osteoclast formation with increased bone mass. Thus, Blimp1 was considered as a therapeutic target to treat skeletal diseases such as osteoporosis (J Biol Chem 2012).
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研究種目 : 基盤研究(C)
研究期間 : 2011~2013
課題番号 : 23592231
研究分野 : 医歯薬学
科研費の分科・細目 : 外科系臨床医学・整形外科学
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