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http://dx.doi.org/10.5352/JLS.2013.23.4.471

Role of NFAT5 in Osteogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells  

Lee, Sun Young (Department of Physiology, School of Medicine, Pusan National University)
Yang, Ji won (Department of Physiology, School of Medicine, Pusan National University)
Jung, Jin Sup (Department of Physiology, School of Medicine, Pusan National University)
Publication Information
Journal of Life Science / v.23, no.4, 2013 , pp. 471-478 More about this Journal
Abstract
Human adipose tissue-derived mesenchymal stem cells (hADSCs) have therapeutic potential, including the ability to self-renew and differentiate into multiple lineages. Understanding of molecular mechanisms of stem cell differentiation is important for improving the therapeutic efficacies of stem cell transplantation. In this study, we determined the role of nuclear factor of activated T cells (NFAT5) in the osteogenic differentiation of hADSCs. The down-regulation of NFAT5 expression by the transfection of a specific siRNA significantly inhibited osteogenic differentiation of hADSCs and decreased the activity of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$) promoter without affecting their proliferation and adipogenic differentiation. The inhibition of NFAT5 expression inhibited the basal and Tumor Necrosis Factor ${\alpha}$ (TNF-${\alpha}$) induced activation of NF-${\kappa}B$, but it did not affect TNF-${\alpha}$-induced degradation of the $I{\kappa}B$ protein. These findings indicate that NFAT5 plays an important role in the osteogenic differentiation of hADSCs through the modulation of the NF-${\kappa}B$ pathway.
Keywords
Human adipose tissue-derived mesenchymal stem cells (hADSCs); osteogenic differentiation; nuclear factor of activated T cells (NFAT5);
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1 Kwon, M. S., Lim, S. W. and Kwon, H. M. 2009. Hypertonic stress in the kidney: a necessary evil. Physiology 24, 186-191.   DOI   ScienceOn
2 Miyakawa, H., Woo, S. K., Dahl, S. C., Handler, J. S. and Kwon, H. M. 1999. Tonicity-responsive enhancer binding protein, a Rel-like protein that stimulates transcription in response to hypertonicity. PNAS 96, 2538-2542.   DOI   ScienceOn
3 Natoli, G. and Chiocca, S. 2008. Nuclear ubiquitin ligases, NF-kappaB degradation, and the control of inflammation. Sci Signal 1, pe1.   DOI   ScienceOn
4 O'Connor, R. S., Mills, S. T., Jones, K. A., Ho, S. N. and Pavlath, G. K. 2006. A combinatorial role for NFAT5 in both myoblast migration and differentiation during skeletal muscle myogenesis. J Cell Sci 120, 149-159.   DOI
5 Ogawa, R., Mizuno, H., Watanabe, A., Migita, M., Shimada, T. and Hyakusoku, H. 2004. Osteogenic and chondrogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice. Biochem Biophys Res Commun 313, 871-877.   DOI   ScienceOn
6 Peng, S., Zhou, G., Lu, K. D., Cheung, K. M., Li, Z., Lam, W. M,, Zhou, Z. and Lu, W. W. 2009. Strontium promotes osteogenic differentiation of mesenchymal stem cells through the Ras/MAPK signaling pathway. Cell Physiol Biochem 23, 165-174.   DOI   ScienceOn
7 Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A, Simonetti, D. W., Craig, S. and Marshak, D. R. 1999. Multilineage potential of adult human mesenchymal stem cells. Science 284, 143-147.   DOI   ScienceOn
8 Prockop, D. J. 1997. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276, 71-74.   DOI   ScienceOn
9 Roth, I., Leroy, V., Kwon, H. M., Martin, P. Y., Feraille, E. and Hasler, U. 2010. Osmoprotective transcription factor NFAT5/TonEBP modulates nuclear factor-${\kappa}B$ activity. Mol Biol Cell 21, 3459-3474.   DOI
10 Strem, B. A., Hicok, K. C., Zhu, M., Wulur, I., Alfonso, Z., Schreiber, R. E., Fraser, J. K. and Hedrick, M. H. 2005. Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med 54, 132-141.   DOI   ScienceOn
11 Woodbury, D., Schwarz, E. J., Prockop, D. J. and Black, I. B. 2000. Adult rat and human bone marrow stromal cells differentiate in to neurons. J Neurosci Res 61, 364-370.   DOI   ScienceOn
12 Zuk, P. A., Zhu, M., Mizuno, H., Huang, J., Futrell, J. W., Katz, A. J., Benhaim, P., Lorenz, H. P. and Hedrick, M. H. 2001. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7, 211-228.   DOI   ScienceOn
13 Yang, Y. I., Kim, H. I., Seo, J. Y. and Choi, M. Y. 2007. Adult stem cells as cell therapeutics of angiogenesis. Tissue Eng Regen Med 4, 484-489.
14 Yoon, H. J., You, S., Yoo, S. A., Kim, N. H., Kwon, H. M., Yoon, C. H., Cho, C. S., Hwang, D. and Kim, W. U. 2011. NFAT5 is a critical regulator of inflammatory arthritis. Arthritis Rheum 63, 1843-1852.   DOI   ScienceOn
15 Zuk, P. A., Zhu, M., Ashjian, P., De Ugarte, D. A., Huang, J. I., Mizuno, H., Alfonso, Z. C., Fraser, J. K., Benhaim, P. and Hedric, M. H. 2002. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13, 4279-4295.   DOI   ScienceOn
16 Cho, H. H., Shin, K. K., Kim. Y. J., Song, J. S., Kim, J. M., Bae, Y. C., Kim, C. D. and Jung, J. S. 2010. NF-kappaB activation stimulates osteogenic differentiation of mesenchymal stem cells derived from human adipose tissue by increasing TAZ expression. J Cell Physiol 223, 168-177.
17 De Ugarte, D. A., Morizono, K., Elbarbary, A., Alfonso, Z., Zuk, P. A., Zhu, M., Dragoo, J. L., Ashjian, P., Thomas, B., Benhaim, P., Chen, I., Fraser, J. and Hedrick, M. H. 2003. Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs 174, 101-109.   DOI   ScienceOn
18 Ferrari, G., Cusella-De A. G., Coletta, M., Paolucci, E., Stornaiuolo, A., Cossu, G. and Mavilio, F. 1998. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279, 1528-1530.   DOI
19 Halvorsen, Y. C., Wilkison, W. O. and Gimble, J. M. 2000. Adipose-derived stromal cells-their utility and potential in bone formation. Int J Obes Relat Metab Disord 24(Suppl 4), S41-44.
20 Halvorsen, Y. D., Franklin, D., Bond, A. L., Hitt, D. C., Auchter, C., Boskey, A. L., Paschalis, E. P., Wilkison, W. O. and Gimble, J. M. 2001. Extracellular matrix mineralization and osteoblast gene expression by human adipose tissue- derived stromal cells. Tissue Eng 7, 729-741.   DOI   ScienceOn
21 Halterman, J. A., Kwon, H. M., Zargham, R., Bortz, P. D. and Wamhoff, B. R. 2011. Nuclear factor of activated T cells 5 regulates vascular smooth muscle cell phenotypic modulation. Arterioscler Thromb Vasc Biol 31, 2287-2296.   DOI   ScienceOn
22 Hayden, M. S. and Ghosh, S. 2008. Shared Principles in NF-${\kappa}B$ signaling. Cell 132, 344-362.   DOI   ScienceOn
23 Hong, J.H., Hwang, E. S., McManus, M. T., Amsterdam, A., Tian, Y., Kalmukova, R., Mueller, E., Benjamin, T., Spiegelman, B. M., Sharp, P. A., Hopkins, N. and Yaffe, M. B. TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science 309, 1074-1078.
24 Jang, E. J., Jeong, H., Han, K. H., Kwon, H. M., Hong, J. H. and Hwang, E. S. TAZ suppresses NFAT5 activity through tyrosine phosphorylation. Mol Biol Cell 32, 4925-4932.
25 Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., Schwartz, R. E., Keene, C. D., Ortizgonzalez, X. R., Reyes, M., Lenvik, T., Lund, T., Blackstad, M., Du, J., Aldrich, S., Lisberg, A., Low, W. C., Largaespada, D. A. and Verfaillie, C. M. 2002. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418, 41-49.   DOI   ScienceOn
26 Jun, Y. J. 2008. Recent development trend and prospects of adipose-derived stem cells on nerve regeneration. Tissue Engineering and Regenerative Medicine 5, 51-56.
27 Kim, J. A., Jeon, U. S., Kwon M. S., Lim, S. W. and Kwon, H. M. 2007. Transcriptional activator TonE-binding protein in cellular protection and differentiation. Methods Enzymol 428, 253-267.   DOI
28 Kuznetsov, S. A., Friedenstein, A. J. and Robey, P. G. 1997. Factors required for bone marrow stromal fibroblast colony formation in vivo. Br J Haematol 97, 561-570.   DOI   ScienceOn
29 Bocker, W., Docheva, D., Prall, W. C., Egea, V., Pappou, E., Rossmann, O., Popov, C., Mutschler, W., Ries, C. and Schieker, M. 2008. IKK-2 is required for TNF-alpha-induced invasion and proliferation of human mesenchymal stem cells. J Mol Med (Berl) 86, 1183-1192.   DOI   ScienceOn
30 Leeman, J. R. and Gilmore, T. D. 2008. Alternative splicing in the NF-kappaB signaling pathway. Gene 423, 97-107.   DOI   ScienceOn
31 Boone, C., Mourot, J., Grégoire, F. and Remacle, C. 2000. The adipose conversion process: regulation by extracellular and intracellular factors. Reprod Nutr Dev 40, 325-358.   DOI   ScienceOn
32 Burg, M., Ferraris, J. and Dmitrieva, M. 2007. Cellular response to hypertonic stress. Physiol Rev 87, 1441-1474.   DOI   ScienceOn