Abstract
Human dental pulp stem cells (DPSCs) have emerged as an important source of stem cells in the tissue engineering, and hypoxia will change various innate characteristics of DPSCs and then affect dental tissue regeneration. Nevertheless, little is known about the complicated molecular mechanisms. In this study, we aimed to investigate the influence and mechanism of miR-140-3p on DPSCs under hypoxia condition. Hypoxia was induced in DPSCs by Cobalt chloride (CoCl2) treatment. The osteo/dentinogenic differentiation capacity of DPSCs was assessed by alkaline phosphatase (ALP) activity, Alizarin Red S staining and main osteo/dentinogenic markers. A luciferase reporter gene assay was performed to verify the downstream target gene of miR-140-3p. This research exhibited that miR-140-3p promoted osteo/dentinogenic differentiation of DPSCs under normoxia environment. Furthermore, miR-140-3p rescued the CoCl2-induced decreased osteo/odontogenic differentiation potentials in DPSCs. Besides, we investigated that miR-140-3p directly targeted lysine methyltransferase 5B (KMT5B). Surprisingly, we found inhibition of KMT5B obviously enhanced osteo/dentinogenic differentiation of DPSCs both under normoxia and hypoxia conditions. In conclusion, our study revealed the role and mechanism of miR-140-3p for regulating osteo/dentinogenic differentiation of DPSCs under hypoxia, and discovered that miR-140-3p and KMT5B might be important targets for DPSC-mediated tooth or bone tissue regeneration.
Highlights
Pulpitis and periapical periodontitis are always irreversible, and nowadays the main therapy is root canal treatment clinically, which has reported with high success rates.[1]
MiR-140-3p was upregulated in CoCl2-induced hypoxia The Mesenchymal stem cells (MSCs) markers of dental pulp stem cells (DPSCs) were verified, which showed that DPSCs were positive for cell surface markers CD90, CD105 and negative for CD34, CD45 (Supplementary Fig. 1)
The miR-140-3p could enhance the osteo/odontogenic differentiation capacity of DPSCs To observe the role of miR-140-3p in DPSCs cultured under normoxia or hypoxia, miR-140-3p inhibitor was transfected into a Control hypoxia-inducible factor-1 (HIF-1) β-actin
Summary
Pulpitis and periapical periodontitis are always irreversible, and nowadays the main therapy is root canal treatment clinically, which has reported with high success rates.[1]. The hypoxia microenvironment has been uncovered to exert great influence on the MSCs functions and effects of tissue regeneration.[7] Researchers have exhibited the different results about whether hypoxia inhibits the osteo/ odontogenic differentiation of dental MSCs. It was reported that characteristics of dental MSCs changed and mineralization decreased under hypoxia.[8,9,10] While other studies showed the totally opposite results in that hypoxia upregulated osteo/ odontogenic-related genes in different kinds of MSCs derived from dental tissues.[11,12] Altogether, the mechanism is still unclear and enhancing MSCs function under hypoxia environments is a key issue for dental tissue regeneration
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