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

被引:13
作者
Tsai, Yo-Hsian [1 ]
Lin, Kuan-Lian [1 ]
Huang, Yuan-Pin [2 ]
Hsu, Yi-Chiang [3 ]
Chen, Chung-Hwan [4 ,5 ]
Chen, Yuhsin [6 ]
Sie, Min-Hua [1 ]
Wang, Gwo-Jaw [4 ,5 ,7 ,8 ]
Lee, Mon-Juan [1 ,9 ]
机构
[1] Chang Jung Christian Univ, Dept Biosci Technol, Tainan 71101, Taiwan
[2] Cheng Shiu Univ, Dept Cosmet & Fash Styling, Kaohsiung, Taiwan
[3] Chang Jung Christian Univ, Taiwan Grad Inst Med Sci, Tainan, Taiwan
[4] Kaohsiung Med Univ, Orthopaed Res Ctr, Kaohsiung, Taiwan
[5] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Orthopaed, Kaohsiung, Taiwan
[6] Execut Yuan, Taichung Dist Agr Res & Extens Stn, Council Agr, Taichung, Taiwan
[7] Natl Cheng Kung Univ Hosp, Dept Orthopaed, Tainan 70428, Taiwan
[8] Univ Virginia, Dept Orthoped Surg, Charlottesville, VA 22903 USA
[9] Chang Jung Christian Univ, Innovat Res Ctr Med, Tainan, Taiwan
关键词
Polyamine; alpha-Difluoromethylornithine (DFMO); Osteogenic differentiation; Small interfering RNA (siRNA); Mesenchymal stem cell; ALPHA-DIFLUOROMETHYLORNITHINE; POLYAMINE DEPLETION; COLORECTAL-CANCER; PROLIFERATION; EXPRESSION; APOPTOSIS; GAMMA; GENE; BIOSYNTHESIS; PREVENTION;
D O I
10.1016/j.febslet.2015.06.023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Omithine decarboxylase (ODC) is the rate-limiting enzyme for polyamine biosynthesis. Suppression of ODC by its irreversible inhibitor, alpha-difluoromethylornithine (DEMO), 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. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:2058 / 2065
页数:8
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