Abstract
BackgroundEpiregulin (EREG) is an important component of EGF and was demonstrated to promote the osteo/dentinogenic differentiation of stem cells from dental apical papilla (SCAPs). Whether EREG can stimulate the osteo/dentinogenic differentiation of dental pulp stem cells (DPSCs) in inflammatory environment is not clear. The purpose of the present study is to investigate the role of EREG on the osteo/dentinogenic differentiation ability of DPSCs in inflammatory environment.MethodsDPSCs were isolated from human third molars. Short hairpin RNAs (shRNAs) were used to knock down EREG expression in DPSCs. Recombinant human EREG (rhEREG) protein was used in the rescue experiment. TNF-α was employed to mimic the inflammatory environment in vitro. Alkaline phosphatase (ALP) staining, Alizarin red staining, quantitative calcium analysis, and real-time RT-PCR were performed to detect osteo/dentinogenic differentiation markers and related signalling pathways under normal and inflammatory conditions.ResultsEREG depletion promoted the ALP activity and mineralization ability of DPSCs. The expression of BSP, DMP-1, and DSPP was also enhanced. Moreover, 50 ng/mL rhEREG treatment decreased the osteo/dentinogenic differentiation potential of DPSCs, while treatment with 10 ng/mL TNF-α for 4 h increased the expression of EREG in DPSCs. Conversely, EREG knockdown rescued the impaired osteo/dentinogenic differentiation ability caused by TNF-α treatment. Further mechanistic studies showed that EREG depletion activated the p38 MAPK and Erk signalling pathways in DPSCs under normal and inflammatory conditions.ConclusionsOur results demonstrated that EREG could inhibit the osteo/dentinogenic differentiation potential of DPSCs via the p38 MAPK and Erk signalling pathways. Under inflammatory environment, EREG depletion enhanced osteo/dentinogenic differentiation potential of DPSCs by improving the expression of p-p38 MAPK and p-Erk.
Highlights
Epiregulin (EREG) is an important component of Epidermal growth factor (EGF) and was demonstrated to promote the osteo/ dentinogenic differentiation of stem cells from dental apical papilla (SCAPs)
Knockdown of EREG enhanced the osteo/dentinogenic differentiation of dental pulp stem cells (DPSCs) To investigate the function of EREG on DPSCs, we knocked down EREG expression in DPSCs using lentiviral vector infection (EREGsh), and Scramsh was used as control
We studied the effect of EREG on the osteo/ dentinogenic differentiation potentials of DPSCs
Summary
Epiregulin (EREG) is an important component of EGF and was demonstrated to promote the osteo/ dentinogenic differentiation of stem cells from dental apical papilla (SCAPs). Based on tissue engineering methods, MSCs can be engrafted to the sites of injury and inflammation; the engraftment efficiency is largely influenced by the local microenvironment, with inflammation being one of the most important factors affecting the regeneration efficiency of MSCs for pulpitis [3]. Both trauma and infection, which result in pulpitis, can lead to an inflammatory microenvironment characterized by the accumulation of inflammatory cells, which release proinflammatory cytokines, including tumour necrosis factor-α (TNF-α) [4, 5]. It is critical to study the functional changes in DPSCs and to identify suitable growth factors to promote the function of DPSCs in the inflammatory microenvironment
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