Melatonin Protects TEGDMA induced Pre-odontoblasts Mitochondrial Apoptosis via JNK/MAPK Signaling Pathway

Abstract Background: Resin monomer induced dental pulp injury presents a mitochondrial dysfunction related pathology. Melatonin has been regarded as a strong mitochondrial protective bioactive compound from pineal gland. However, it remains unknown whether melatonin can prevent dental pulp from resin monomer induced injury. The aim of the study is to investigate the effects of melatonin on TEGDMA, a major component in dental resin, induced mouse pre-odontoblast cell lines (mDPC6T) mitochondrial apoptosis and to verify whether JNK/MAPK signaling pathway mediate the protective effect of melatonin. Methods: We adopted a well-established TEGDMA-induced mDPC6T apoptosis model to investigate the preventive effect of melatonin by detecting cell viability, apoptosis rate, expression of apoptosis related protein, mitochondrial ROS (mtROS) production, mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) level. Inhibitors of MAPKs signaling were used to explore which pathway was participated in TEGDMA induced apoptosis. Finally, we verified the role of JNK/MAPK pathway during the protective effects of melatonin above by the agonist and antagonists of JNK.Results: Melatonin attenuated TEGDMA induced mDPC6T apoptosis via reducing mtROS production, rescuing MMP and ATP level. Meanwhile, the mitochondrial dysfunction and apoptosis was alleviated by the JNK/MAPK inhibitor SP600125 but not the other MAPKs signaling inhibitors. Furthermore, melatonin down-regulated the expression of phosphorylated-JNK, and eliminated the active effects of Anisomycin on JNK/MAPK pathway, which mimicked the effects of the SP600125.Conclusion: Our findings demonstrated that melatonin protected mDPC6T against TEGDMA induced apoptosis via JNK/MAPK signaling and maintenance of mitochondrial function, which presented a novel therapeutic strategy for prevention against resin monomer-induced dental pulp injury.