Research Papers: Gerotarget (Focus on Aging):
Drug-induced premature senescence model in human dental follicle stem cells
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Yuanfen Zhai1,*, Rongbin Wei1,*, Junjun Liu1, Huihui Wang2, Wenping Cai1, Mengmeng Zhao1, Yongguang Hu1, Shuwei Wang3, Tianshu Yang1, Xiaodong Liu4, Jianhua Yang1 and Shangfeng Liu1,3
1 Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, P. R. China
2 Department of Pediatric Dentistry, School of Stomatology, Tongji University, Shanghai Engineering Research Center, Shanghai, P. R. China
3 Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, P. R. China
4 Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, P. R. China
* These authors have contributed equally to this work
Shangfeng Liu, email:
Jianhua Yang, email:
Xiaodong Liu, email:
Keywords: aging; dental stem cells; cellular senescence model; stress; DNA damage; Gerotarget
Received: September 18, 2016 Accepted: December 12, 2016 Published: December 21, 2016
Aging is identified by a progressive decline of physiological integrity leading to age-related degenerative diseases, but its causes is unclear. Human dental pulp stem cells (hDPSCs) has a remarkable rejuvenated capacity that relies on its resident stem cells. However, because of the lack of proper senescence models, exploration of the underlying molecular mechanisms has been hindered. Here, we established a cellular model utilizing a hydroxyurea (HU) treatment protocol and effectively induced Human dental pulp stem cells to undergo cellular senescence. Age-related phenotypic changes were identified by augmented senescence-associated-β-galactosidase (SA-β-gal) staining, declined proliferation and differentiation capacity, elevated G0/G1 cell cycle arrest, increased apoptosis and reactive oxygen species levels. Furthermore, we tested the expression of key genes in various DNA repair pathways including nonhomologous end-joining (NHEJ) and homologous recombination (HR) pathways. In addition, our results showed that Dental pulp stem cells from young donors are more resistant to apoptosis and exhibit increased non-homologous end joining activity compared to old donors. Further transcriptome analysis demonstrate that multiple pathways are involved in the HU-induced Dental pulp stem cells ageing, including genes associated with DNA damage and repair, mitochondrial dysfunction and increased reactive oxygen species levels. Taken together, the cellular model have important implications for understanding the molecular exploration of Dental pulp stem cells senescence and aging.
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