Age-Dependent Impaired Neurogenic Differentiation Capacity of Dental Stem Cell is Associated with Wnt/β-Catenin Signaling
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Two kinds of dental stem cells (DSCs), dental pulp stem cells (DPSCs) and stem cells from human-exfoliated deciduous teeth (SHED), have been identified as novel populations of mesenchymal stem cells that can be induced to differentiate into osteoblasts, chondrocytes, adipocytes, and neuron-like cells in vitro. As we know, both of them originate from the neural crest, but have distinct characteristics and functions in vitro and in vivo. The regeneration potential of DSCs declines with advanced age; however, the mechanism of the impaired potential in DSCs has not been fully explored. In this study, we investigated whether declined neurogenic differentiation capacity is associated with an altered expression of Wnt signaling-related proteins in vitro. We compared stem cells isolated from human dental pulp in two age groups: the exfoliated deciduous teeth (5–12 years), and the third permanent teeth (45–50 years). We found that the expression levels of neuron markers, such as βIII-tubulin, microtubule-associated protein 2(MAP2), tyrosine hydroxylase (TH), and Nestin were lower in the DPSCs group compared with that in the SHED group; however, in supplementation with human recombinant Wnt1 in the medium, the DPSCs were prone to neural differentiation and expressed higher levels of neurogenic markers. In summary, our study demonstrated that Wnt/β-catenin signaling may play a vital role in the age-dependent neural differentiation of DSCs. Therefore, DSCs may provide an ideal source of stem cells that can further extend their therapeutic application in nerve injury and neurodegenerative diseases.
KeywordsAge-dependent Dental pulp stem cells Neurogenic differentiation Wnt/β-Catenin signaling
This study was supported by grants from the Chinese National Natural Science Foundation (No. 81172841), the Natural Science Foundation of Jiangsu Colleges and Universities Grant (09KJB320010) (10KJB320012); the “Top Six Types of Talents” Financial Assistance of Jiangsu Province Grant (Nos. 6 and 7); and the Jiangsu Province’s Outstanding Medical Academic Leader Program (LJ201136, LJ201135).
- Muthna D, Soukup T, Vavrova J, Mokry J, Cmielova J, Visek B, Jiroutova A, Havelek R, Suchanek J, Filip S, English D, Rezacova M (2010) Irradiation of adult human dental pulp stem cells provokes activation of p53, cell cycle arrest, and senescence but not apoptosis. Stem Cells Dev 19:1855–1862PubMedCrossRefGoogle Scholar
- Sakai K, Yamamoto A, Matsubara K, Nakamura S, Naruse M, Yamagata M, Sakamoto K, Tauchi R, Wakao N, Imagama S, Hibi H, Kadomatsu K, Ishiguro N, Ueda M (2012) Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms. J Clin Invest 122(1):80–90PubMedGoogle Scholar
- Tamaki Y, Nakahara T, Ishikawa H, Sato S (2012) In vitro analysis of mesenchymal stem cells derived from human teeth and bone marrow. Odontology [Epub ahead of print]Google Scholar
- Venkataramana NK, Pal R, Rao SA, Naik AL, Jan M, Nair R, Sanjeev CC, Kamble RB, Murthy DP, Chaitanya K (2012) Bilateral transplantation of allogenic adult human bone marrow-derived mesenchymal stem cells into the subventricular zone of parkinson’s disease: a pilot clinical study. Stem Cells Int 2012:931920Google Scholar