title: Suppression of ornithine decarboxylase promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.
abstract: Ornithine decarboxylase (ODC) is the rate-limiting enzyme for polyamine biosynthesis. Suppression of ODC by its irreversible inhibitor, α-difluoromethylornithine (DFMO), or by RNA interference through siRNA, enhanced osteogenic gene expression and alkaline phosphatase activity, and accelerated matrix mineralization of human bone marrow-derived mesenchymal stem cells (hBMSCs). Besides, adipogenic gene expression and lipid accumulation was attenuated, indicating that the enhanced osteogenesis was accompanied by down-regulation of adipogenesis when ODC was suppressed. A decrease in the intracellular polyamine content of hBMSCs during osteogenic induction was observed, suggesting that the level of endogenous polyamines is regulated during differentiation of hBMSCs. This study elucidates the role of polyamine metabolism in the lineage commitment of stem cells and provides a potential new indication for DFMO as bone-stimulating drug.
authors.affiliation: Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan.
authors.forename: Yo-Hsian
authors.initials: YH
authors.lastname: Tsai
authors.affiliation: Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan.
authors.forename: Kuan-Lian
authors.initials: KL
authors.lastname: Lin
authors.affiliation: Department of Cosmetics and Fashion Styling, Cheng Shiu University, Kaohsiung, Taiwan.
authors.forename: Yuan-Pin
authors.initials: YP
authors.lastname: Huang
authors.affiliation: Taiwan Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan, Taiwan.
authors.forename: Yi-Chiang
authors.initials: YC
authors.lastname: Hsu
authors.affiliation: Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chung-Hwan
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Taichung District Agricultural Research and Extension Station, Council of Agriculture, Executive Yuan, Taichung, Taiwan.
authors.forename: Yuhsin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan.
authors.forename: Min-Hua
authors.initials: MH
authors.lastname: Sie
authors.affiliation: Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Orthopaedics, National Cheng Kung University Hospital, Tainan, Taiwan; Department of Orthopedic Surgery, University of Virginia, VA, USA.
authors.forename: Gwo-Jaw
authors.initials: GJ
authors.lastname: Wang
authors.affiliation: Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan; Innovative Research Center of Medicine, Chang Jung Christian University, Tainan, Taiwan. Electronic address: mjlee@mail.cjcu.edu.tw.
authors.forename: Mon-Juan
authors.initials: MJ
authors.lastname: Lee
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001857:Bone Matrix / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000518:Eflornithine / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D050356:Lipid Metabolism / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000737:chemistry / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects; D011700:Putrescine / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism
chemical_list: D065108:Ornithine Decarboxylase Inhibitors; D034741:RNA, Small Interfering; D013096:Spermine; D009955:Ornithine Decarboxylase; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine
keywords: Mesenchymal stem cell; Osteogenic differentiation; Polyamine; Small interfering RNA (siRNA); α-Difluoromethylornithine (DFMO)