Effects of melatonin on the proliferation and differentiation of human dental pulp cells

Liu, Qin; Fan, Wenguo; He, Yifan; Zhang, Fuping; Guan, Xiaoyan; Deng, Qianyi; Lu, Xianjun; He, Hongwen; Huang, Fang

doi:10.1016/j.archoralbio.2017.06.034

Cited by 23 publications

(24 citation statements)

References 34 publications

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“…Based on cell viability assays, H 2 O 2 at 500 μmol/L, which reduced viability of hDPCs by approximately 40%, was selected for other experiments. Our previous study showed that physiological concentrations of melatonin (10 −12 , 10 −10 , 10 −8 mol/L) could inhibit proliferation of hDPCs 18 . In the present study, the administration of physiological concentrations of melatonin for 24 h reduced hDPCs viability by 16–20%, and synergistically enhanced the H 2 O 2 -induced reduction in viability of hDPCs in a concentration-dependent manner.…”

Section: Discussionsupporting

confidence: 64%

“…Our previous studies show that physiological concentrations of melatonin can inhibit proliferation and promote odontogenic differentiation of hDPCs, 18 but its effect on apoptosis remains unknown. Here, we used H 2 O 2 to induce apoptosis in hDPCs, aiming to explore the effect of physiological concentrations of melatonin on H 2 O 2 -induced toxicity.…”

Section: Introductionmentioning

confidence: 99%

“…It is involved in many important biological processes like circadian regulation, immune modulation, anti-inflammation, neuroprotection, and tumor suppression 12, 13, 14, 15. It also regulates multiple cellular processes such as the proliferation and differentiation of various cell types 16, 17, 18. Moreover, accumulating evidence suggests that melatonin also regulates apoptosis in different cell types.…”

Section: Introductionmentioning

confidence: 99%

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Melatonin enhances hydrogen peroxide-induced apoptosis in human dental pulp cells

Deng

Liu

Zhang

et al. 2019

Journal of Dental Sciences

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Background/purposeMelatonin, at physiological concentrations, was previously found to inhibit proliferation and promote odontogenic differentiation in human dental pulp cells (hDPCs), but its effect on apoptosis is unclear. Our study aimed to investigate the effect of melatonin on the H2O2-mediated viability reduction and apoptosis in hDPCs.Materials and methodshDPCs were treated with H2O2 (0, 250, 500, 1000 μmol/L), melatonin (0, 10−12, 10−10, 10−8 mol/L), and melatonin with H2O2 for 24 h. CCK-8 assays were performed to evaluate cell viability. Apoptosis was measured by DAPI and Annexin V/propidium iodide staining. Intracellular reactive oxygen species (ROS) were measured by CellROX® staining and mitochondrial membrane potential (ΔΨm) was examined by JC-1 staining.ResultsH2O2 obviously decreased the viability of hDPCs in a concentration-dependent manner and melatonin alone also reduced viability by 16–20%. Melatonin was also found to enhance H2O2-induced toxicity in a concentration-dependent manner, and the highest physiological concentration of melatonin (10−8 mol/L) had the most obvious effect (P < 0.001). Treating H2O2-exposed hDPCs with melatonin significantly increased the ratio of apoptotic cells with condensed and deformed nuclei (P < 0.001), as well as the percentage of Annexin V-positive cells (P < 0.01). Furthermore, melatonin significantly increased intracellular ROS levels and induced the loss of ΔΨm in H2O2-exposed cells (P < 0.05).ConclusionOur results indicate that melatonin, at physiological concentrations, can enhance H2O2-induced apoptosis in hDPCs and increase H2O2-mediated ROS production and ΔΨm loss. Further studies are needed to investigate whether melatonin targets the mitochondrial death pathway during the process.

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Melatonin enhances hydrogen peroxide-induced apoptosis in human dental pulp cells

Deng

Liu

Zhang

et al. 2019

Journal of Dental Sciences

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“… 48 that melatonin at 1 mM significantly improved the semen quality of bovine 48 . The result indicates that melatonin’s effect at physiological concentrations in vitro may be specific only for certain types of cells 49 .…”

Section: Discussionmentioning

confidence: 97%

Melatonin promotes triacylglycerol accumulation via MT2 receptor during differentiation in bovine intramuscular preadipocytes

Yang

Tang

Wang

et al. 2017

Sci Rep

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Melatonin (N-acetyl-5-methoxytryptamine) is a derivative of tryptophan which is produced and secreted mainly by the pineal gland and regulates a variety of important central and peripheral actions. To examine the potential effects of melatonin on the proliferation and differentiation of bovine intramuscular preadipocytes (BIPs), BIPs were incubated with different concentrations of melatonin. Melatonin supplementation at 1 mM significantly increased peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein (C/EBP) β, and C/EBPα expression and promoted the differentiation of BIPs into adipocytes with large lipid droplets and high cellular triacylglycerol (TAG) levels. Melatonin also significantly enhanced lipolysis and up-regulated the expression of lipolytic genes and proteins, including hormone sensitive lipase (HSL), adipocyte triglyceride lipase (ATGL), and perilipin 1 (PLIN1). Moreover, melatonin reduced intracellular reactive oxygen species (ROS) levels by increasing the expression levels and activities of superoxide dismutase 1 (SOD1) and glutathione peroxidase 4 (GPX4). Finally, the positive effects of melatonin on adipogenesis, lipolysis, and redox status were reversed by treatment with luzindole, anantagonist of nonspecific melatonin receptors 1 (MT1) and 2 (MT2), and 4-phenyl-2-propionamidotetraline (4P-PDOT), a selective MT2 antagonist. These results reveal that melatonin promotes TAG accumulation via MT2 receptor during differentiation in BIPs.

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“…Our previous study has shown that MT at physiological concentrations could promote odontogenic differentiation of hDPCs [ 22 ]. It is proved that DNA methylation involved in the regulation of differentiation of hDPCs, and MT activity was modulated by the epigenetic factors in MSCs as mentioned before.…”

Section: Introductionmentioning

confidence: 99%

Melatonin-induced suppression of DNA methylation promotes odontogenic differentiation in human dental pulp cells

Deng

Fan

et al. 2020

Bioengineered

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Differentiation potency of human dental pulp cells (hDPCs) is essential for dentin regeneration. DNA methylation is one of the major epigenetic mechanisms and is suggested to involve in differentiation of hDPCs, the machinery of which includes DNA methyltransferase enzymes (DNMTs) and methyl-CpG-binding domain proteins (MBDs). Our previous study has found that melatonin (MT) promoted hDPC differentiation, but its mechanism remains elusive. We aimed to investigate the role of DNA methylation in the promotion of MT to differentiation of hDPCs in vitro . hDPCs were cultured in basal growth medium (CO) or odontogenic medium (OM) exposed to MT at different concentrations (0, 10 −12 , 10 −10 , 10 −8 , 10 −6 , 10 −4 M). The cell growth was analyzed using Cell Counting Kit-8 assay, and mineralized tissue formation was measured using Alizarin red staining. The expression of the 10 genes ( DNMT1, DNMT3A, DNMT3B, MBD1-6, MeCP2 ) was determined using real-time qPCR and western blotting. The abundance of MeCP2 in the nuclei was evaluated using immunofluorescence analysis. Global methylation level was tested using ELISA. We found that mineralized tissue formation significantly increased in OM with MT at 10 −4 M, while the levels of MeCP2 and global DNA methylation level declined. The expression of MBD1, MBD3, and MBD4 significantly increased in OM alone, and the expession of DNMT1 and MBD2 was decreased. These results indicate that MT promotes odontogenic differentiation of hDPCs in vitro by regulating the levels of DNMT1, MeCP2, and global DNA methylation, suggesting that MT-induced DNA methylation machinery may play an important role in tooth regeneration.

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Effects of melatonin on the proliferation and differentiation of human dental pulp cells

Cited by 23 publications

References 34 publications

Melatonin enhances hydrogen peroxide-induced apoptosis in human dental pulp cells

Melatonin enhances hydrogen peroxide-induced apoptosis in human dental pulp cells

Melatonin promotes triacylglycerol accumulation via MT2 receptor during differentiation in bovine intramuscular preadipocytes

Melatonin-induced suppression of DNA methylation promotes odontogenic differentiation in human dental pulp cells

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