演題詳細

一般口演 / Oral Session

一般口演 15 (Oral Session 15) :造血環境

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日程
2013年10月11日(金)
時間
10:00 - 11:30
会場
第13会場 / Room No.13 (札幌市教育文化会館 3F 研修室301)
座長・司会
北島 健二 (Kenji Kitajima):1
1:東京臨床医学総合研究所 幹細胞プロジェクト
 
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Role of matrix-embedded osteocytes in hematopoietic stem/progenitor cell niche regulation

演題番号 : OS-1-72

浅田 騰 (Noboru Asada):1,2、片山 義雄 (Yoshio Katayama):2、佐藤 真理 (Mari Sato):2、皆川 健太郎 (Kentaro Minagawa):2、若橋 香奈子 (Kanako Wakahashi):2、川野 宏樹 (Hiroki Kawano):2、川野 裕子 (Yuko Kawano):2、定 明子 (Akiko Sada):2、松井 利充 (Toshimitsu Matsui):2、谷本 光音 (Mitsune Tanimoto):1

1:Dept. of Hematology/Oncology, Okayama Univ., Japan、2:Dept. of Hematology, Kobe Univ., Japan

 

Hematopoietic stem/progenitor cell (HSPC) migration out of the specific bone marrow (BM) niche to the circulation is a critical process for clinical stem cell transplantation. G-CSF induces mobilization of HSPC by modulating the signaling components in the BM, such as sympathetic nervous system (SNS) and macrophages, to the endosteal niche. Here, we demonstrate that osteocytes are novel regulators of osteoblastic niche from inside the bone matrix. Gene expression analysis revealed that osteocytes responded more rapidly than osteoblasts to G-CSF. This is likely via the SNS since surgical sympathectomy interrupts this response. Indeed, G-CSF disrupts the projections toward osteoblasts in β2-adrenergic receptor positive osteocytes near the endosteum, suggesting that G-CSF-induced sympathetic tone suppresses supportive signals from osteocytes to osteoblasts prior to mobilization. Targeted ablation of osteocytes, as well as klotho hypomorphic mice with disrupted osteocyte network, displayed a severe mobilization defect. Osteocyte ablation led to the diminishment of osteomac which has been shown to be a niche regulator, and induced HSC quiescence possibly through the upregulation of cxcl12 mRNA in the perivascular niche cells, some of which were osteoblast precursors. These results indicate that the niche located at the interface between the BM and bone is critically controlled from both the BM side and inside the bone. We propose the presence of a continuous syncytium of niche pool consisted of osteolineage cells spreading from inside the bone tissue through the central BM.

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