title: p16(INK4A) mediates age-related changes in mesenchymal stem cells derived from human dental pulp through the DNA damage and stress response.
abstract: 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 β-galactosidase (SA-β-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 γ-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.
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Xingmei
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Guijuan
authors.initials: G
authors.lastname: Feng
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Suzhe
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Division of Gastroenterology and Hepatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China. Electronic address: larry017@163.com.
authors.forename: Liren
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Division of Gastroenterology and Hepatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China. Electronic address: guzhifeng@126.com.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D016922:Cellular Senescence; D002648:Child; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D004249:DNA Damage; D003782:Dental Pulp / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D015398:Signal Transduction
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: Age-related; Dental pulp; Mesenchymal stem cell; P16(INK4A); Senescence