title: Bortezomib enhances the osteogenic differentiation capacity of human mesenchymal stromal cells derived from bone marrow and placental tissues.
abstract: Bortezomib (BZB) is a chemotherapeutic agent approved for treating multiple myeloma (MM) patients. In addition, there are several reports showing that bortezomib can induce murine mesenchymal stem cells (MSCs) to undergo osteogenic differentiation and increase bone formation in vivo. MSCs are the multipotent stem cells that have capacity to differentiate into several mesodermal derivatives including osteoblasts. Nowadays, MSCs mostly bone marrow derived have been considered as a valuable source of cell for tissue replacement therapy. In this study, the effect of bortezomib on the osteogenic differentiation of human MSCs derived from both bone marrow (BM-MSCs) and postnatal sources such as placenta (PL-MSCs) were investigated. The degree of osteogenic differentiation of BM-MSCs and PL-MSCs after bortezomib treatment was assessed by alkaline phosphatase (ALP) activity, matrix mineralization by Alizarin Red S staining and the expression profiles of osteogenic differentiation marker genes, Osterix, RUNX2 and BSP. The results showed that 1 nM and 2 nM BZB can induce osteogenic differentiation of BM-MSCs and PL-MSCs as demonstrated by increased ALP activity, increased matrix mineralization and up-regulation of osteogenic differentiation marker genes, Osterix, RUNX2 and BSP as compared to controls. The enhancement of osteogenic differentiation of MSCs by bortezomib may lead to the potential therapeutic applications in human diseases especially patients with osteopenia.
authors.affiliation: Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand.
authors.forename: Tanwarat
authors.initials: T
authors.lastname: Sanvoranart
authors.affiliation: Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand. Electronic address: mtajr@mahidol.ac.th.
authors.forename: Aungkura
authors.initials: A
authors.lastname: Supokawej
authors.affiliation: Division of Cell Biology, Department of Pre-clinical Sciences, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.
authors.forename: Pakpoom
authors.initials: P
authors.lastname: Kheolamai
authors.affiliation: Division of Hematology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Yaowalak
authors.initials: Y
authors.lastname: U-Pratya
authors.affiliation: Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Nuttha
authors.initials: N
authors.lastname: Klincumhom
authors.affiliation: Division of Cell Biology, Department of Pre-clinical Sciences, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.
authors.forename: Sirikul
authors.initials: S
authors.lastname: Manochantr
authors.affiliation: Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Methichit
authors.initials: M
authors.lastname: Wattanapanitch
authors.affiliation: Division of Hematology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Electronic address: surapolsi@gmail.com.
authors.forename: Surapol
authors.initials: S
authors.lastname: Issaragrisil
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000469:Alkaline Phosphatase / Q000378:metabolism; D001851:Bone Diseases, Metabolic / Q000188:drug therapy; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D005260:Female; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D010024:Osteoporosis / Q000188:drug therapy; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D011719:Pyrazines / Q000494:pharmacology*; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001897:Boronic Acids; D050659:Core Binding Factor Alpha 1 Subunit; D058574:Integrin-Binding Sialoprotein; D011719:Pyrazines; C493709:RUNX2 protein, human; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D000069286:Bortezomib; D000469:Alkaline Phosphatase
keywords: Bone marrow; Bortezomib; Mesenchymal stromal cells; Osteogenic differentiation; Placenta