Diverse Effects of Lead Nitrate on the Proliferation, Differentiation, and Gene Expression of Stem Cells Isolated from a Dental Origin

Abstract

Lead (Pb2+) exposure continues to be a significant public health problem. Therefore, it is vital to have a continuous epidemiological dataset for a better understanding of Pb2+ toxicity. In the present study, we have exposed stem cells isolated from deciduous and permanent teeth, periodontal ligament, and bone marrow to five different types of Pb2+ concentrations (160, 80, 40, 20, and 10 µM) for 24 hours to identify the adverse effects of Pb2+ on the proliferation, differentiation, and gene expression on these cell lines. We found that Pb2+ treatment altered the morphology and adhesion of the cells in a dose-dependent manner. There were no significant changes in terms of cell surface phenotypes. Cells exposed to Pb2+ continued to differentiate into chondrogenesis and adipogenesis, and a severe downregulation was observed in osteogenesis. Gene expression studies revealed a constant expression of key markers associated with stemness (Oct 4, Rex 1) and DNA repair enzyme markers, but downregulation occurred with some ectoderm and endoderm markers, demonstrating an irregular and untimely differentiation trail. Our study revealed for the first time that Pb2+ exposure not only affects the phenotypic characteristics but also induces significant alteration in the differentiation and gene expression in the cells.

The protective effect of the aqueous extract of Sida acuta BURM.F on lead nitrate-induced genotoxicity

“…They threaten human health as they easily enter human body through the food chain. Lead (Pb 2+ ) is one of the most toxic heavy metals (Abdullah et al 2014). Lead moves into and throughout ecosystems and contaminate the vegetation, air, water and soil (Samal et al 2017).…”

Systems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor Cells

“…Cell differentiation requires strict regulation of gene expression in order to ensure correct cell fate. Some studies report lead exposure impact on embryonic stem cells differentiation (Huang and Schneider, 2004; Abdullah et al, 2014; Senut et al, 2014). In a study involving embryonic stem cells cultivated with lead acetate 10 μM for 5 days, the authors observed significant proliferation inhibition in neurospheres collected from rat brain regions (Huang and Schneider, 2004).…”

Reciprocal Effect of Environmental Stimuli to Regulate the Adipogenesis and Osteogenesis Fate Decision in Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs)

“…In vivo, Pb 2+ (50 ppm) exposure from conception to the age of 18 weeks reduced bone mass and promoted adipogenesis while decreasing osteogenesis in Long-Evans rats, in part through the inhi bition of the Wnt/β-catenin signaling pathway [74]. In vitro, exposure to higher levels o Pb 2+ (40-160 µ M) for 24 hours downregulated osteogenesis in hBM-MSCs and dental pulp stem cells [71]. In contrast, during the differentiation of 3T3-L1 fibroblasts, Pb 2+ treatmen at lower concentrations (5 and 10 µ M) for eight days increased lipid accumulation accom panied by the increase in mRNA expression of Pparγ and Plin1 [73], as well as C/ebpβ (a gene upstream of Pparγ) expression [73].…”

“…Pb 2+ not only shares the same ion transporter as Ca 2+ , but also acts as a competitive inhibitor of Ca 2+ when entering and leaving bone [70]. Exposure to Pb 2+ reduced femoral bone density in a rat model and inhibited osteoblastic activity in hBM-MSCs [71][72][73]. In vivo, Pb 2+ (50 ppm) exposure from conception to the age of 18 weeks reduced bone mass and promoted adipogenesis while decreasing osteogenesis in Long-Evans rats, in part through the inhibition of the Wnt/β-catenin signaling pathway [74].…”