Deoxynivalenol induces the p21-mediated G₂/M arrest and upregulation of differentiation markers in human dental pulp stem cells.
TL;DR
This is the first study that provides direct in vitro evidence of Don induced cell cycle arrest at G2/M phase through highly upregulated p21, with no increase in p53 protein levels, suggesting p53-independent p21 induction.
Abstract
Humans are constantly exposed to mycotoxins primarily through contaminated food. Deoxynivalenol (DON) is the most frequently occurring, and its toxicity to stem cells remains unclear. Mesenchymal stem cells (MSCs), responsible for tissue regeneration, serve as tools for regenerative therapies and valuable models for studying cellular differentiation and toxicological responses. This study investigated the cytotoxic effects of DON on the cell cycle progression and differentiation in human dental pulp stem cells (DPSCs). DPSCs, isolated from healthy embedded third-molar teeth and characterized, were treated with DON (0.25-16 µg/mL). Cell viabilities were determined via MTT assay and the inhibitory concentrations (IC50 and IC25) of DON were calculated (0.46 μg/mL and 0.23 μg/mL). Cell death, ROS levels, cell cycle progression, and adipogenic and osteogenic differentiation of DPSCs were evaluated under DON exposure. DON did not induced cell death or oxidative stress in DPSCs. However, DON induced cell cycle arrest at G2/M phase through highly upregulated (6-fold) p21, with no increase in p53 protein levels, suggesting p53-independent p21 induction. Moreover, DON increased the expression of early differentiation markers (BMP2 and C/EBPβ) under non-induced culture conditions. This is the first study that provides direct in vitro evidence of DON on the cell cycle progression and differentiation in DPSCs.
