ID 109810
タイトルヨミ
TACE カッセイ セイギョ ニヨル タンキュウ ブンカ ノ ケッテイ
タイトル別表記
Determination of a Differentiation Fate of Monocytes by the TACE Activity
著者
日浅, 雅博 徳島大学大学院ヘルスバイオサイエンス研究部生体材料工学分野 徳島大学 教育研究者総覧 KAKEN研究者をさがす
キーワード
TACE
TIMP3
骨髄間質細胞
樹状細胞
多発性骨髄腫
資料タイプ
学術雑誌論文
抄録
Multiple myeloma (MM) almost exclusively expands in the bone marrow and generates devastating bone destruction. We recently reported that GM-CSF and IL-4, an inducer of dendritic cell (DC) differentiation, up-regulate TNFα converting enzyme (TACE) expression in monocytes to cleave their surface M-CSF receptor (M-CSFR), which drastically disrupts osteoclastogenesis. Because TACE activity is inhibited by TIMP3, we explored the expression of TIMP3 and its role in monocyte differentiation into osteoclasts and DCs in MM. Bone marrow stromal cells (BMSCs) secreted a large amount of TIMP3 protein whose production was further enhanced by IL-6 and TGFβ over-produced in MM bone lesions. BMSCs potently suppressed GM-CSF and IL-4-induced DC differentiation and resumed osteoclastogenesis from monocytes along with the suppression of surface M-CSFR and RANK shedding on monocytes. TIMP3 knockdown in BMSCs by TIMP3 siRNA enhanced M-CSFR shedding in monocytes in the presence of BMSCs and resumed GM-CSF and IL-4-mediated DC differentiation from monocytes, suggesting monocyte differentiation skewed by BMSC-derived TIMP3. These results suggest that TIMP3 over-produced in MM bone marrow microenvironment restores surface M-CSFR on monocytes to facilitate their downstream signaling, which causes extensive bone destruction and impaired DC differentiation in MM. TIMP3 may therefore become a novel target in the treatment of MM bone disease.
掲載誌名
四国歯学会雑誌
ISSN
09146091
cat書誌ID
AN10050046
出版者
四国歯学会
24
2
開始ページ
13
終了ページ
19
並び順
13
発行日
2012-01-31
フルテキストファイル
言語
jpn
著者版フラグ
出版社版
部局
歯学系