Notch1 signaling regulates the proliferation and self-renewal of human dental follicle cells by modulating the G1/S phase transition and telomerase activity

Chen, Xuepeng, Zhang, Tianhou, Shi, Jiejun, Xu, Ping, Gu, Zexu, Sandham, Andrew, Yang, Lei, and Ye, Qingsong (2013) Notch1 signaling regulates the proliferation and self-renewal of human dental follicle cells by modulating the G1/S phase transition and telomerase activity. PLoS ONE, 8 (7). e69967. pp. 1-10.

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Abstract

Multipotent human dental follicle cells (HDFCs) have been intensively studied in periodontal regeneration research, yet the role of Notch1 in HDFCs has not been fully understood. The aim of the current study is to explore the role of Notch1 signaling in HDFCs self-renewal and proliferation. HDFCs were obtained from the extracted wisdom teeth from adolescent patients. Regulation of Notch1 signaling in the HDFCs was achieved by overexpressing the exogenous intracellular domain of Notch1 (ICN1) or silencing Notch1 by shRNA. The regulatory effects of Notch1 on HDFC proliferation, cell cycle distribution and the expression of cell cycle regulators were investigated through various molecular technologies, including plasmid construction, retrovirus preparation and infection, qRT-PCR, western blot, RBP-Jk luciferase reporter and cell proliferation assay. Our data clearly show that constitutively activation of Notch1 stimulates the HDFCs proliferation while inhibition of the Notch1 suppresses their proliferation in vitro. In addition, the HDFCs proliferation is associated with the increased expression of cell cycle regulators, e.g. cyclin D1, cyclin D2, cyclin D3, cyclin E1, CDK2, CDK4, CDK6, and SKP2 and the decreased expression of p27 kip1. Moreover, our data show that the G1/S phase transition (indicating proliferation) and telomerase activity (indicating self-renewal) can be enhanced by overexpression of ICN1 but halted by inhibition of Notch1. Together, the current study provides evidence for the first time that Notch1 signaling regulates the proliferation and self-renewal capacity of HDFCs through modulation of the G1/S phase transition and the telomerase activity.

Item ID: 28782
Item Type: Article (Research - C1)
ISSN: 1932-6203
Funders: Zhejiang Provincial Natural Science Foundation of China, Scientific Research Fund of Zhejiang Provincial Education Department, Scientific Research Fund of Zhejiang Provincial Health Department, Traditional Chinese Medicine Science Research Fund of Zhejiang Province
Projects and Grants: No. LQ12H14001, No.Y200909021, No. 2012KYA126, No. 2012ZB101
Date Deposited: 19 Aug 2013 00:23
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1105 Dentistry > 110506 Orthodontics and Dentofacial Orthopaedics @ 30%
11 MEDICAL AND HEALTH SCIENCES > 1105 Dentistry > 110508 Periodontics @ 30%
11 MEDICAL AND HEALTH SCIENCES > 1116 Medical Physiology > 111601 Cell Physiology @ 40%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920113 Oro-Dental Disorders @ 100%
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