Title : Lead inhibits the odontogenic differentiation potential of dental pulp stem cells by affecting WNT1/?-catenin signaling and related miRNAs expression
Abstract:
Lead (Pb) is a global health problem for humans. Environmental Pb exposure results in blood, saliva, bone, and teeth lead accumulation. Mineralized calcium-rich tissues are the main reservoir of body Pb. Different studies have shown the Pb effect on odontogenesis and teeth homeostasis. Indeed, long-term cumulative Pb exposure is associated with different dental disorders such as tooth loss, and dental caries. However, the mechanisms of lead-induced dental toxicity are still largely unknown. Recent studies have suggested that miRNAs play a key regulatory role in odontogenesis. They affect the translation of specific target mRNAs and involve in the regulation of many cellular processes. In the present study, we attempted to assess the Pb effect on odontogenic differentiation of isolated human dental pulp stem cells and further understand the underlying mechanism of Pb-induced dental differentiation abnormalities related to aberrant miRNA expression, focused on Wnt signaling pathway genes as the master regulators in tooth development. The isolation of dental pulp cells was achieved using healthy, freshly extracted human wisdom teeth through enzymatic digestion. The mineralized formation capacity was assessed using Alizarin red staining and alkaline phosphatase assay and qRT-PCR analysis. Our results showed that exposure to Pb resulted in reduced odontogenic marker alkaline phosphatase activity and calcium deposition. Also, diminished expression of RUNX2, DMP1, and DSPP, as well as Wnt signaling mediators including WNT1, and β-catenin were detected. The expression of Wnt signaling-related microRNAs, miRNA-139-5p and miRNA-142-3p were shown to have a significant increase. We concluded that Pb could adversely affect the odontogenic differentiation potential of dental pulp stem cells. The underlying mechanism might be related to Pb-induced epigenetic dysregulation of WNT1/β-catenin pathway-related miRNAs leading to down-regulation of Wnt/β-catenin related odontogenic genes and eventually impaired odontogenic differentiation process.
Audience Take Away Notes:
- Lead is widely distributed in our environment and is responsible for many health issues, including dental diseases. Our currents data on the adverse effect of lead on dental stem cell function further proving the cariogenic potential of lead. The data suggest for audience to prevent pb exposure by living and working in Pb free areas, adopting a healthy lifestyle free from smoking and alcohol drinking, the factors found to contribute to Pb-induced dental diseases.
- The result of current study provides important data for dentists, strategy makers and researchers in regenerative medicine. Considering the scarce epidemiological data regarding the adverse effect of lead on dental health, our data using in vitro cell culture systems further indicate the aberrant differentiation of dental pulp stem cells exposed to lead that is associated with increase in risk of dental caries.
- On the other hand, dental pulp stem cells have been studied in regenerative medicine in autologous stem cells therapies. Our results may have some implications and precaution for using stem cells isolated from patient exposed to high level of lead.
- Our results showed the epigenotoxic effect of lead exposure as an underlying mechanism of lead toxicity on dental stem cell function. The results suggest the causative role of epigenetic modifications in the etiology of diseases associated with lead toxicity thus we propose a direction for further research to focus on epigenetic therapy.
