IADR Abstract Archives
TMEM110 and P2X7R-MTOR Signalling Pathways Orchestrate Melatonin-Increased Autophagy to Facilitate Osteogenesis of Inflamed PDLSCs
Objectives: Periodontal ligament stem cells (PDLSCs) bring new hope for patients with poor periodontium recovery and impaired regeneration. However, the complex inflammatory microenvironment continually inhibits stem cell function and hinders stem cell therapy effectiveness. Melatonin is a naturally occurring neurohormone involved in the regulation of multiple biological functions.
Methods: In this study, we investigated the effect of melatonin on periodontium regeneration both in vitro and in vivo. H&E and masson staining, western blot analysis, qRT-PCR, mRNA-sequence analysis, flow cytometric analysis, fluorescence microscope analysis and TEM assay were used in this study.
Results: We found that melatonin injection promoted periodontium recovery in a rat LPS-induced periodontitis model in rats. Melatonin at a concentration range from 0.5 to 5.0 μM promotes osteogenic differentiation of PDLSCs in a dose-dependent manner in an inflammatory microenvironment. After mRNA-sequence and subsequent KEGG and GO analysis, we found that autophagy was upregulated in melatonin treated PDLSCs, and autophagy played an positive role in osteogenesis of PDLSCs. Melatonin restores damaged cell autophagy and osteogenesis of PDLSCs in an inflammatory microenvironment through TMEM110. What’s more, P2X7 receptor expression were also increased after melatonin treatment, the activation of P2X7 receptor triggered mTOR-ULK pathway and inhibiting autophagy in PDLSCs, which maintains the balance of PDLSCs after melatonin treatment. The inhibition of P2X7R or mTOR increased the apoptosis of PDLSCs in an inflammatory microenvironment after treatment with 5 μM melatonin.
Conclusions: Collectively, the results of our study provide evidence for melatonin-mediated osteogenesis of inflamed PDLSCs being important to periodontal tissue regeneration. Moreover, melatonin as a therapeutic drug for periodontitis deserves to be investigated through clinical studies.
Methods: In this study, we investigated the effect of melatonin on periodontium regeneration both in vitro and in vivo. H&E and masson staining, western blot analysis, qRT-PCR, mRNA-sequence analysis, flow cytometric analysis, fluorescence microscope analysis and TEM assay were used in this study.
Results: We found that melatonin injection promoted periodontium recovery in a rat LPS-induced periodontitis model in rats. Melatonin at a concentration range from 0.5 to 5.0 μM promotes osteogenic differentiation of PDLSCs in a dose-dependent manner in an inflammatory microenvironment. After mRNA-sequence and subsequent KEGG and GO analysis, we found that autophagy was upregulated in melatonin treated PDLSCs, and autophagy played an positive role in osteogenesis of PDLSCs. Melatonin restores damaged cell autophagy and osteogenesis of PDLSCs in an inflammatory microenvironment through TMEM110. What’s more, P2X7 receptor expression were also increased after melatonin treatment, the activation of P2X7 receptor triggered mTOR-ULK pathway and inhibiting autophagy in PDLSCs, which maintains the balance of PDLSCs after melatonin treatment. The inhibition of P2X7R or mTOR increased the apoptosis of PDLSCs in an inflammatory microenvironment after treatment with 5 μM melatonin.
Conclusions: Collectively, the results of our study provide evidence for melatonin-mediated osteogenesis of inflamed PDLSCs being important to periodontal tissue regeneration. Moreover, melatonin as a therapeutic drug for periodontitis deserves to be investigated through clinical studies.
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