TET1 knockdown inhibits the odontogenic differentiation potential of human dental pulp cells

Human dental pulp cells (hDPCs) possess the capacity to differentiate into odontoblast-like cells and generate reparative dentin in response to exogenous stimuli or injury. Ten–eleven translocation 1 (TET1) is a novel DNA methyldioxygenase that plays an important role in the promotion of DNA demethylation and transcriptional regulation in several cell lines. However, the role of TET1 in the biological functions of hDPCs is unknown. To investigate the effect of TET1 on the proliferation and odontogenic differentiation potential of hDPCs, a recombinant shRNA lentiviral vector was used to knock down TET1 expression in hDPCs. Following TET1 knockdown, TET1 was significantly downregulated at both the mRNA and protein levels. Proliferation of the hDPCs was suppressed in the TET1 knockdown groups. Alkaline phosphatase activity, the formation of mineralized nodules, and the expression levels of DSPP and DMP1 were all reduced in the TET1-knockdown hDPCs undergoing odontogenic differentiation. Based on these results, we concluded that TET1 knockdown can prevent the proliferation and odontogenic differentiation of hDPCs, which suggests that TET1 may play an important role in dental pulp repair and regeneration. A protein that promotes cell proliferation and differentiation may play a key role in dentin regeneration and repair. Human dental pulp cells (hDPCs) are multipotent stem cells found in the soft tissue inside teeth; they differentiate into other cell types to generate new dentin following injury or infection. Qiong Xu at Sun Yat-sen University in Guangzhou, China, and co-workers investigated a recently discovered protein called TET1 to determine its role in hDPCs during dentin repair. TET1 is known to be expressed in hDPCs, and has been shown to regulate differentiation in various other cell types. The team disabled the TET1 gene, which resulted in reduced expression of TET1 in hDPCs. The loss of TET1 appeared to decrease the hDPCs’ growth rate and prevented differentiation by reducing the expression of key genes and limiting mineralization.