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Hypoxia enhances osteogenic differentiation in retinoic acid-treated murine-induced pluripotent stem cells

  • Original Article
  • Cell Biology
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Hypoxic condition influences biological responses in various cell types. However, a hypoxic regulating osteogenic differentiation remains controversy. Here, an influence of short-term culture in hypoxic condition on osteogenic marker gene expression by retinoic acid-treated murine gingival fibroblast-derived induced pluripotent stem cells (RA-miPS) was investigated. Results demonstrated that hypoxic condition significantly upregulated Vegf, Runx2, Osx, and Ocn mRNA expression by RA-miPS in normal culture medium at day 3. Further, desferrioxamine significantly downregulated pluripotent marker (Nanog and Oct4) and enhanced osteogenic marker (Runx2, Osx, Dlx5, and Ocn) gene expression as well as promoted in vitro mineral deposition. However, the effect of cobalt chloride on osteogenic differentiation of RA-miPS was not robust. In summary, the results imply that hypoxic condition may be useful in the enhancement of osteogenic differentiation in RA-miPS.

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References

  1. Hakim F, Kaitsuka T, Raeed JM, Wei FY, Shiraki N, Akagi T, et al. High oxygen condition facilitates the differentiation of mouse and human pluripotent stem cells into pancreatic progenitors and insulin-producing cells. J Biol Chem 2014;289:9623–9638.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Medley TL, Furtado M, Lam NT, Idrizi R, Williams D, Verma PJ, et al. Effect of oxygen on cardiac differentiation in mouse iPS cells:role of hypoxia inducible factor-1 and Wnt/beta-catenin signaling. PLoS One 2013;8:e80280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Iida K, Takeda-Kawaguchi T, Hada M, Yuriguchi M, Aoki H, Tamaoki N, et al. Hypoxia-enhanced derivation of iPSCs from human dental pulp cells. J Dent Res 2013;92:905–910.

    Article  CAS  PubMed  Google Scholar 

  4. Sugimoto K, Yoshizawa Y, Yamada S, Igawa K, Hayashi Y, Ishizaki H. Effects of hypoxia on pluripotency in murine iPS cells. Microsc Res Tech 2013;76:1084–1092.

    Article  CAS  PubMed  Google Scholar 

  5. Wion D, Christen T, Barbier EL, Coles JA. PO(2) matters in stem cell culture. Cell Stem Cell 2009;5:242–243.

    Article  CAS  PubMed  Google Scholar 

  6. Yoshida Y, Takahashi K, Okita K, Ichisaka T, Yamanaka S. Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell 2009;5:237–241.

    Article  CAS  PubMed  Google Scholar 

  7. Fotia C, Massa A, Boriani F, Baldini N, Granchi D. Prolonged exposure to hypoxic milieu improves the osteogenic potential of adipose derived stem cells. J Cell Biochem 2015;116:1442–1453.

    Article  CAS  PubMed  Google Scholar 

  8. Zhang QB, Zhang ZQ, Fang SL, Liu YR, Jiang G, Li KF. Effects of hypoxia on proliferation and osteogenic differentiation of periodontal ligament stem cells:an in vitro and in vivo study. Genet Mol Res 2014;13:10204–10214.

    Article  CAS  PubMed  Google Scholar 

  9. Osathanon T, Vivatbutsiri P, Sukarawan W, Sriarj W, Pavasant P, Sooampon S. Cobalt chloride supplementation induces stem-cell marker expression and inhibits osteoblastic differentiation in human periodontal ligament cells. Arch Oral Biol 2015;60:29–36.

    Article  CAS  PubMed  Google Scholar 

  10. Cicione C, Muiños-López E, Hermida-Gómez T, Fuentes-Boquete I, Díaz-Prado S, Blanco FJ. Effects of severe hypoxia on bone marrow mesenchymal stem cells differentiation potential. Stem Cells Int 2013;2013:232896.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Egusa H, Kayashima H, Miura J, Uraguchi S, Wang F, Okawa H, et al. Comparative analysis of mouse-induced pluripotent stem cells and mesenchymal stem cells during osteogenic differentiation in vitro. Stem Cells Dev 2014;23:2156–2169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lou X. Induced pluripotent stem cells as a new strategy for osteogenesis and bone regeneration. Stem Cell Rev 2015;11:645–651.

    Article  CAS  PubMed  Google Scholar 

  13. Egusa H, Okita K, Kayashima H, Yu G, Fukuyasu S, Saeki M, et al. Gingival fibroblasts as a promising source of induced pluripotent stem cells. PLoS One 2010;5:e12743.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ren H, Cao Y, Zhao Q, Li J, Zhou C, Liao L, et al. Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions. Biochem Biophys Res Commun 2006;347:12–21.

    Article  CAS  PubMed  Google Scholar 

  15. Zhang W, Wu Y, Yan Q, Ma F, Shi X, Zhao Y, et al. Deferoxamine enhances cell migration and invasion through promotion of HIF-1a expression and epithelial-mesenchymal transition in colorectal cancer. Oncol Rep 2014;31:111–116.

    CAS  PubMed  Google Scholar 

  16. Ramakrishnan S, Anand V, Roy S. Vascular endothelial growth factor signaling in hypoxia and inflammation. J Neuroimmune Pharmacol 2014;9:142–160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Liu L, Gao J, Yuan Y, Chang Q, Liao Y, Lu F. Hypoxia preconditioned human adipose derived mesenchymal stem cells enhance angiogenic potential via secretion of increased VEGF and bFGF. Cell Biol Int 2013;37:551–560.

    Article  CAS  PubMed  Google Scholar 

  18. Teramura T, Onodera Y, Takehara T, Frampton J, Matsuoka T, Ito S, et al. Induction of functional mesenchymal stem cells from rabbit embryonic stem cells by exposure to severe hypoxic conditions. Cell Transplant 2013;22:309–329.

    Article  PubMed  Google Scholar 

  19. Bilousova G, Jun du H, King KB, De Langhe S, Chick WS, Torchia EC, et al. Osteoblasts derived from induced pluripotent stem cells form calcified structures in scaffolds both in vitro and in vivo. Stem Cells 2011;29:206–216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yu Y, Al-Mansoori L, Opas M. Optimized osteogenic differentiation protocol from R1 mouse embryonic stem cells in vitro. Differentiation 2015;89:1–10.

    Article  CAS  PubMed  Google Scholar 

  21. Liu C, Weaver J, Liu KJ. Rapid conditioning with oxygen oscillation:neuroprotection by intermittent normobaric hyperoxia after transient focal cerebral ischemia in rats. Stroke 2012;43:220–226.

    Article  CAS  PubMed  Google Scholar 

  22. Schofield CJ, Ratcliffe PJ. Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol 2004;5:343–354.

    Article  CAS  PubMed  Google Scholar 

  23. Yuan Y, Hilliard G, Ferguson T, Millhorn DE. Cobalt inhibits the interaction between hypoxia-inducible factor-alpha and von Hippel-Lindau protein by direct binding to hypoxia-inducible factor-alpha. J Biol Chem 2003;278:15911–15916.

    Article  CAS  PubMed  Google Scholar 

  24. Triantafyllou A, Liakos P, Tsakalof A, Georgatsou E, Simos G, Bonanou S. Cobalt induces hypoxia-inducible factor-1alpha (HIF-1alpha) in HeLa cells by an iron-independent, but ROS-, PI-3K-and MAPK-dependent mechanism. Free Radic Res 2006;40:847–856.

    Article  CAS  PubMed  Google Scholar 

  25. Woo KJ, Lee TJ, Park JW, Kwon TK. Desferrioxamine, an iron chelator, enhances HIF-1alpha accumulation via cyclooxygenase-2 signaling pathway. Biochem Biophys Res Commun 2006;343:8–14.

    Article  CAS  PubMed  Google Scholar 

  26. Agis H, Watzek G, Gruber R. Prolyl hydroxylase inhibitors increase the production of vascular endothelial growth factor by periodontal fibroblasts. J Periodontal Res 2012;47:165–173.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Mineralized Tissue Research Unit and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand

    Jeeranan Manokawinchoke, Thanaphum Osathanon & Prasit Pavasant

  2. Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Japan

    Hiroshi Egusa

Authors
  1. Jeeranan Manokawinchoke
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  2. Thanaphum Osathanon
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  3. Hiroshi Egusa
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  4. Prasit Pavasant
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Correspondence to Thanaphum Osathanon or Prasit Pavasant.

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Manokawinchoke, J., Osathanon, T., Egusa, H. et al. Hypoxia enhances osteogenic differentiation in retinoic acid-treated murine-induced pluripotent stem cells. Tissue Eng Regen Med 13, 547–553 (2016). https://doi.org/10.1007/s13770-016-9127-9

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  • DOI: https://doi.org/10.1007/s13770-016-9127-9

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