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Stem Cell Reports. 2014 Oct 14;3(4):566-73. doi: 10.1016/j.stemcr.2014.08.002. Epub 2014 Sep 18.

Activation of p38, p21, and NRF-2 mediates decreased proliferation of human dental pulp stem cells cultured under 21% O2.

Author information

1
Department of Physiology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain.
2
Department of Odontology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain.
3
Cardiovascular Division, British Heart Foundation Centre of Research Excellence, School of Medicine, King's College London, London SE1 9NH, UK.
4
Department of Physiology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain. Electronic address: jose.vina@uv.es.

Abstract

High rates of stem cell proliferation are important in regenerative medicine and in stem cell banking for clinical use. Ambient oxygen tensions (21% O2) are normally used for in vitro culture, but physiological levels in vivo range between 3% and 6% O2. We compared proliferation of human dental pulp stem cells (hDPSCs) cultured under 21% versus 3% O2. The rate of hDPSC proliferation is significantly lower at 21% O2 compared to physiological oxygen levels due to enhanced oxidative stress. Under 21% O2, increased p38 phosphorylation led to activation of p21. Increased generation of reactive oxygen species and p21 led to activation of the NRF-2 signaling pathway. The upregulation of NRF-2 antioxidant defense genes under 21% O2 may interact with cell-cycle-related proteins involved in regulating cell proliferation. Activation of p38/p21/NRF-2 in hDPSCs cultured under ambient oxygen tension inhibits stem cell proliferation and upregulates NRF-2 antioxidant defenses.

PMID:
25358785
PMCID:
PMC4223702
DOI:
10.1016/j.stemcr.2014.08.002
[Indexed for MEDLINE]
Free PMC Article

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