Journal
LEUKEMIA RESEARCH
Volume 38, Issue 8, Pages 970-976Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2014.05.022
Keywords
Mesenchymal stem cells; Notch1; Osteogenic differentiation; Multiple myeloma; Carfilzomiba
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Funding
- National Natural Science Foundation of China [81172256, 81272631, 81102466]
- Applied Basic Research Programs of Suzhou City [SYS201132]
- China Postdoctoral Science Foundation [2014M550307, 2014M551650]
- Foundation for Doctors and Returned Scholars of Second Affiliated Hospital of Soochow University [SDFEYBS1106]
- Jiangsu Province's Key Medical Department
- Priority Academic Program Development of Jiangsu Higher Education Institutions
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signaling plays a key role in the differentiation of mesenchymal stem cells (MSCs). Carfilzomib(CFZ), a second-generation proteasome inhibitor, has potent cytotoxicity against myeloma cells. In this study, we investigated the effects of CFZ on the osteogenic differentiation potential of MSCs derived from myeloma patients (MM-MSCs) in vitro. MM-MSCs showed decreased osteogenic differentiation ability, together with an impairment of notch1 deactivation. The notch1 inhibitor DAPT and the downregulation of notch1 by shRNA promoted osteogenesis in MM-MSCs. Additionally, CFZ treatment resulted in notch1 inhibition and enhanced osteogenesis in MM-MSCs. These findings suggest that CFZ stimulates osteogenesis via notch1 inhibition. (C) 2014 Elsevier Ltd. All rights reserved.
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