Journal of Cellular Biochemistry

Exogenous polyamines promote osteogenic differentiation by reciprocally regulating osteogenic and adipogenic gene expression

Authors

  • Mon-Juan Lee,

    Corresponding author
    1. Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan
    • Correspondence to: Mon-Juan Lee, Department of Bioscience Technology, Chang Jung Christian University, No. 1, Changda Rd., Gueiren District, Tainan 71101, Taiwan.

      E-mail: mjlee@mail.cjcu.edu.tw

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  • Yuhsin Chen,

    1. Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan
    2. Taichung District Agricultural Research and Extension Station, Council of Agriculture, Executive Yuan, Taichung, Taiwan
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  • Yuan-Pin Huang,

    1. Department of Cosmetics and Fashion Styling, Cheng Shiu University, Kaohsiung, Taiwan
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  • Yi-Chiang Hsu,

    1. Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan, Taiwan
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  • Lan-Hsin Chiang,

    1. Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan
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  • Tzu-Yu Chen,

    1. Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan
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  • Gwo-Jaw Wang

    1. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
    3. Department of Orthopaedics, National Cheng Kung University Hospital, Tainan, Taiwan
    4. Department of Orthopedic Surgery, University of Virginia, Charlottesville, Virginia
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  • The authors confirm that there is no conflict of interest.

ABSTRACT

Polyamines are naturally occurring organic polycations that are ubiquitous in all organisms, and are essential for cell proliferation and differentiation. Although polyamines are involved in various cellular processes, their roles in stem cell differentiation are relatively unexplored. In this study, we found that exogenous polyamines, putrescine, spermidine, and spermine, promoted osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) without inducing cell death or apoptosis. Alkaline phosphatase (ALP) activity and the mRNA level of osteogenic genes, including Runx2, ALP, osteopontin, and osteocalcin, were up-regulated by exogenous polyamines. When hBMSCs were cultured at high cell density favoring adipocyte formation, exogenous polyamines resulted in down-regulation of adipogenic genes such as PPARγ, aP2, and adipsin. Extracellular matrix mineralization, a marker for osteoblast maturation, was enhanced in the presence of exogenous polyamines, while lipid accumulation, an indication of adipogenic differentiation, was attenuated. Exogenous polyamines increased the mRNA expression of polyamine-modulated factor 1 (PMF-1) and its downstream effector, spermidine/spermine N1-acetyltransferase (SSAT), while that of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, was suppressed. These results lead to possible connections between polyamine metabolism and osteogenic differentiation pathways. To summarize, this study provides evidence for the involvement of polyamines in osteogenic differentiation of hBMSCs, and is the first to demonstrate that osteogenic and adipogenic differentiation are reciprocally regulated by exogenous polyamines. J. Cell. Biochem. 114: 2718–2728, 2013. © 2013 Wiley Periodicals, Inc.

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