Journal
MECHANISMS OF AGEING AND DEVELOPMENT
Volume 141, Issue -, Pages 46-55Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2014.09.004
Keywords
Age-related; Dental pulp; Mesenchymal stem cell; P16(INK4A); Senescence
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Funding
- Chinese National Natural Science Foundation [81172841]
- Natural Science Foundation of Jiangsu Colleges and Universities Grant [09KJB320010, 10KJB320012]
- Top Six Types of Talents, Jiangsu Province Grant
- Jiangsu Province's Outstanding Medical Academic Leader Program [LJ201136, LJ201135]
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Mesenchymal stem cells derived from human dental pulp (DP-MSCs) are characterized by self-renewal and multi-lineage differentiation, which play important roles in regenerative medicine. Autologous transfers, as non-immunogenic, constitute the safest approach in cellular transplantations. However, their use may be limited by age-related changes. In the study, we compared DP-MSCs isolated from human in five age groups: 5-12 y, 12-20 y, 20-35 y, 35-50 y, and >50 y. We tested the effect of age on proliferation, differentiation, senescence-associated beta-galactosidase (SA-beta-gal), cell cycle and programmed cell death. DP-MSCs showed characteristics of senescence as a function of age. Meanwhile, the expression of p16(INK4A) and gamma-H2A.X significantly increased with age, whereas heat shock protein 60 (HSP60) was decreased in the senescent DP-MSCs. Reactive oxygen species (ROS) staining showed the number of ROS-stained cells and the DCFH fluorescent level were higher in the aged group. Further we examined the senescence of DP-MSCs after modulating p16(INK4A) signaling. The results indicated the dysfunction of DP-MSCs was reversed by P16(INK4A) siRNA. In summary, our study indicated p16(INK4A) pathway may play a critical role in DP-MSCs age-related changes and the DNA damage response (DDR) and stress response may be the main mediators of DP-MSCs senescence induced by excessive activation of p16(INK4A) signaling. (C) 2014 Published by Elsevier Ireland Ltd.
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