Suppression of ornithine decarboxylase promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells

Yo-Hsian Tsai; Kuan-Lian Lin; Yuan-Pin Huang; Yi-Chiang Hsu; Chung-Hwan Chen; Yuhsin Chen; Min-Hua Sie; Gwo-Jaw Wang; Mon-Juan Lee

doi:10.1016/j.febslet.2015.06.023

Suppression of ornithine decarboxylase promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells

FEBS Lett. 2015 Jul 22;589(16):2058-65. doi: 10.1016/j.febslet.2015.06.023. Epub 2015 Jun 30.

Authors

Yo-Hsian Tsai¹, Kuan-Lian Lin¹, Yuan-Pin Huang², Yi-Chiang Hsu³, Chung-Hwan Chen⁴, Yuhsin Chen⁵, Min-Hua Sie¹, Gwo-Jaw Wang⁶, Mon-Juan Lee⁷

Affiliations

¹ Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan.
² Department of Cosmetics and Fashion Styling, Cheng Shiu University, Kaohsiung, Taiwan.
³ Taiwan Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan, Taiwan.
⁴ Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁵ Taichung District Agricultural Research and Extension Station, Council of Agriculture, Executive Yuan, Taichung, Taiwan.
⁶ 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.
⁷ 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.

PMID: 26140984
DOI: 10.1016/j.febslet.2015.06.023

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.

Keywords: Mesenchymal stem cell; Osteogenic differentiation; Polyamine; Small interfering RNA (siRNA); α-Difluoromethylornithine (DFMO).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipogenesis / drug effects
Bone Marrow Cells / cytology
Bone Marrow Cells / drug effects
Bone Marrow Cells / metabolism
Bone Matrix / chemistry
Bone Matrix / drug effects
Bone Matrix / metabolism
Calcification, Physiologic / drug effects
Cell Proliferation / drug effects
Cells, Cultured
Eflornithine / pharmacology
Gene Expression Regulation, Developmental / drug effects
Humans
Kinetics
Lipid Metabolism / drug effects
Mesenchymal Stem Cells / cytology*
Mesenchymal Stem Cells / drug effects
Mesenchymal Stem Cells / metabolism
Ornithine Decarboxylase / chemistry
Ornithine Decarboxylase / metabolism*
Ornithine Decarboxylase Inhibitors / pharmacology
Osteogenesis* / drug effects
Putrescine / metabolism
RNA Interference
RNA, Small Interfering
Spermidine / metabolism
Spermine / metabolism

Substances

Ornithine Decarboxylase Inhibitors
RNA, Small Interfering
Spermine
Ornithine Decarboxylase
Spermidine
Putrescine
Eflornithine