Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2136625 | Leukemia Research | 2014 | 7 Pages |
•An impairment of notch1 deactivation in MM-MSCs was found.•CFZ promoted osgeogenic potential of MM-MSCs.•CFZ stimulates osteogenesis via notch1 inhibition in MSCs.
Notch1 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.