title: Carfilzomib promotes the osteogenic differentiation potential of mesenchymal stem cells derived from myeloma patients by inhibiting notch1 activity in vitro.
abstract: 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.
authors.affiliation: Department of Hematology, Second Affiliated Hospital of Soochow University, Suzhou, Jiang Su 215004, PR China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hematology, Second Affiliated Hospital of Soochow University, Suzhou, Jiang Su 215004, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Basic Medicine and Biology Science of Soochow University, Suzhou, Jiang Su 215004, PR China.
authors.forename: Wenzhuo
authors.initials: W
authors.lastname: Zhuang
authors.affiliation: Department of Hematology, Second Affiliated Hospital of Soochow University, Suzhou, Jiang Su 215004, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Hematology, Second Affiliated Hospital of Soochow University, Suzhou, Jiang Su 215004, PR China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Ge
authors.affiliation: Department of Hematology, Second Affiliated Hospital of Soochow University, Suzhou, Jiang Su 215004, PR China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Second Affiliated Hospital of Soochow University, Suzhou, Jiang Su 215004, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Hematology, Second Affiliated Hospital of Soochow University, Suzhou, Jiang Su 215004, PR China.
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Hematology, Second Affiliated Hospital of Soochow University, Suzhou, Jiang Su 215004, PR China. Electronic address: lbzwz0907@hotmail.com.
authors.forename: Bingzong
authors.initials: B
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008875:Middle Aged; D009101:Multiple Myeloma / Q000473:pathology*; D009842:Oligopeptides / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects*; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C497761:NOTCH1 protein, human; D009842:Oligopeptides; D051881:Receptor, Notch1; C524865:carfilzomib
keywords: Carfilzomib; Mesenchymal stem cells; Multiple myeloma; Notch1; Osteogenic differentiation