Browse > Article
http://dx.doi.org/10.5352/JLS.2016.26.12.1355

Improvement of Neuronal Differentiation by PDE4 Inhibition in Human Bone Marrow-mesenchymal Stem Cells  

Jeong, Da Hee (Department of Biology, College of Natural Science, Chosun University)
Joe, I-Seul (Department of Biology, College of Natural Science, Chosun University)
Cho, Goang-Won (Department of Biology, College of Natural Science, Chosun University)
Publication Information
Journal of Life Science / v.26, no.12, 2016 , pp. 1355-1359 More about this Journal
Abstract
Human bone marrow mesenchymal stem cells (hBM-MSCs) can differentiate into various cell types including osteoblasts, adipocytes, chondrocytes, and myocytes. Previous studies, including our own, have shown that MSCs can also differentiate into neuron-like cells. However, their rate of neuronal differentiation is not sufficient for application to stem cell therapy, which requires well-defined cell types. For this purpose, we first examined the expression of neuronal lineage markers (GFAP, MAP-2, KCNH1, Nestin, NF-M, and Tuj-1) by real-time PCR, western blot, and immunocytochemical staining. The expressions of the astrocyte marker GFAP and neuronal markers NF-M and Tuj-1 increased in neuronal differentiated MSCs (dMSCs). To improve the neuronal differentiation efficiency, PDE4, an important signaling intermediator in the progression of neuronal differentiation, was modulated using well-known inhibitors such as rolipram or resveratrol and then differentiated into neuronal cells (Roli- or RSV-dMSCs). The expressions of NF-M, Tuj-1 were increased while that of GFAP decreased in Roli- and RSV-dMSCs, which were examined by real-time PCR, western blot, and immunocytochemical staining. From these experiments, we have found that the neuronal differentiation efficiency can be ameliorated by the modulation of PDE4 activity.
Keywords
hBM-MSCs; neuronal differentiation; PDE4 inhibition; resveratrol; rolipram;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Atkins, C. M., Oliva, A. A. Jr., Alonso, O. F., Pearse, D. D., Bramlett, H. M. and Dietrich, W. D. 2007. Modulation of the cAMP signaling pathway after traumatic brain injury. Exp. Neurol. 208, 145-158.   DOI
2 Caplan, A. I. 2007. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J. Cell. Physiol. 213, 341-347.   DOI
3 Csiszar, A., Labinskyy, N., Pinto, J. T., Ballabh, P., Zhang, H., Losonczy, G., Pearson, K., de Cabo, R., Pacher, P., Zhang, C. and Ungvari, Z. 2009. Resveratrol induces mitochondrial biogenesis in endothelial cells. Am. J. Physiol. Heart Circ. Physiol. 297, H13-20.   DOI
4 DeMarch, Z., Giampa, C., Patassini, S., Martorana, A., Bernardi, G. and Fusco, F. R. 2007. Beneficial effects of rolipram in a quinolinic acid model of striatal excitotoxicity. Neurobiol. Dis. 25, 266-273.   DOI
5 Garcia-Osta, A., Cuadrado-Tejedor, M., Garcia-Barroso, C., Oyarzabal, J. and Franco, R. 2012. Phosphodiesterases as therapeutic targets for Alzheimer's disease. ACS Chem. Neurosci. 3, 832-844.   DOI
6 Hannila, S. S. and Filbin, M. T. 2008. The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury. Exp. Neurol. 209, 321-332.   DOI
7 Huang, Z. and Mancini, J. A. 2006. Phosphodiesterase 4 inhibitors for the treatment of asthma and COPD. Curr. Med. Chem. 13, 3253-3262.   DOI
8 Jeong, S. G., Ohn, T., Kim, S. H. and Cho, G. W. 2013. Valproic acid promotes neuronal differentiation by induction of neuroprogenitors in human bone-marrow mesenchymal stromal cells. Neurosci. Lett. 554, 22-27.   DOI
9 Joe, I. S., Jeong, S. G. and Cho, G. W. 2015. Resveratrol-induced SIRT1 activation promotes neuronal differentiation of human bone marrow mesenchymal stem cells. Neurosci. Lett. 584, 97-102.   DOI
10 Khurana, S., Venkataraman, K., Hollingsworth, A., Piche, M. and Tai, T. C. 2013. Polyphenols: benefits to the cardiovascular system in health and in aging. Nutrients 5, 3779-3827.   DOI
11 Krause, W., Kuhne, G. and Sauerbrey, N. 1990. Pharmacokinetics of (+)-rolipram and (-)-rolipram in healthy volunteers. Eur. J. Clin. Pharmacol. 38, 71-75.   DOI
12 Neumann, S. and Woolf, C. J. 1999. Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron 23, 83-91.   DOI
13 Neumann, S., Bradke, F., Tessier-Lavigne, M. and Basbaum, A. I. 2002. Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron 34, 885-893.   DOI
14 Normann, C. and Berger, M. 2008. Neuroenhancement: status quo and perspectives. Eur. Arch. Psychiatry Clin. Neurosci. 258 Suppl 5, 110-114.   DOI
15 Park, S. J., Ahmad, F., Philp, A., Baar, K., Williams, T., Luo, H., Ke, H., Rehmann, H., Taussig, R., Brown, A. L., Kim, M. K., Beaven, M. A., Burgin, A. B., Manganiello, V. and Chung, J. H. 2012. Resveratrol ameliorates aging-related meta-bolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 148, 421-433.   DOI
16 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
17 Price, N. L., Gomes, A. P., Ling, A. J., Duarte, F. V., Martin- Montalvo, A., North, B. J., Agarwal, B., Ye, L., Ramadori, G., Teodoro, J. S., Hubbard, B. P., Varela, A. T., Davis, J. G., Varamini, B., Hafner, A., Moaddel, R., Rolo, A. P., Coppari, R., Palmeira, C. M., de Cabo, R., Baur, J. A. and Sinclair, D. A. 2012. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab. 15, 675-690.   DOI
18 Qiu, J., Cai, D., Dai, H., McAtee, M., Hoffman, P. N., Bregman, B. S. and Filbin, M. T. 2002. Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 34, 895-903.   DOI
19 Woodbury, D., Schwarz, E. J., Prockop, D. J. and Black, I. B. 2000. Adult rat and human bone marrow stromal cells differentiate into neurons. J. Neurosci. Res. 61, 364-370.   DOI
20 Zhang, L., Seitz, L. C., Abramczyk, A. M., Liu, L. and Chan, C. 2011. cAMP initiates early phase neuron-like morphology changes and late phase neural differentiation in mesenchymal stem cells. Cell Mol. Life Sci. 68, 863-876.   DOI