ID 109810
Title Transcription
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
Title Alternative
Determination of a Differentiation Fate of Monocytes by the TACE Activity
Author
Hiasa, Masahiro Department of Biomaterials and Bioengineering, Institute of Health Biosciences, The University of Tokushima Graduate School Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Keywords
TACE
TIMP3
骨髄間質細胞
樹状細胞
多発性骨髄腫
Content Type
Journal Article
Description
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.
Journal Title
四国歯学会雑誌
ISSN
09146091
NCID
AN10050046
Publisher
四国歯学会
Volume
24
Issue
2
Start Page
13
End Page
19
Sort Key
13
Published Date
2012-01-31
FullText File
language
jpn
TextVersion
Publisher
departments
Oral Sciences