Department of Oral Anatomy and Physiology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.
Eur Rev Med Pharmacol Sci. 2019 Jul;23(13):5967-5979. doi: 10.26355/eurrev_201907_18343.
The aim of this study was to investigate the effect of melatonin on mitochondria of dental papilla cells (DPCs) during the odontogenic differentiation process.
Primary DPCs were obtained from the first molar dental papilla of neonatal rats and cultured in osteogenic (OS) or basal medium supplemented with melatonin at different concentrations (0, 1 pM, 0.1 nM, 10 nM, and 1 μM) for differentiation in vitro. Effects of melatonin on differentiation, mitochondrial respiratory function, and mitochondrial biogenesis of DPCs were analyzed.
Upon odontogenic induction, Alkaline phosphatase (ALP) activity, dentin sialophosphoprotein (DSPP), and dentin matrix protein (DMP1) expression were significantly enhanced, with a peaked expression at 10 nM of melatonin treatment. During DPCs differentiation, 10 nM melatonin could significantly induce the increase of intracellular Adenosine triphosphate (ATP), the decrease of the oxidized form of nicotinamide adenine dinucleotide (NAD+)/NADH ratio and reactive oxygen species (ROS). The mRNA and protein levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1), and mitochondrial transcription factor A (TFAM) were significantly increased, and the peak level of expression was found in cells treated with 10 nM of melatonin. Furthermore, the mitochondria DNA (mtDNA) copy number was significantly decreased during DPCs differentiation.
These findings suggest that melatonin can promote the differentiation of rat DPCs and regulate mitochondrial energy metabolism, ROS scavenging, and mitochondrial biogenesis.
本研究旨在探讨褪黑素在牙乳头细胞（DPC）的成牙分化过程中线粒体的作用。
原代 DPC 取自新生大鼠第一磨牙牙乳头，在成骨（OS）或基础培养基中培养，并加入不同浓度（0、1 pM、0.1 nM、10 nM 和 1 μM）的褪黑素进行体外分化。分析褪黑素对 DPC 分化、线粒体呼吸功能和线粒体生物发生的影响。
在牙向诱导后，碱性磷酸酶（ALP）活性、牙本质涎磷蛋白（DSPP）和牙本质基质蛋白 1（DMP1）的表达显著增强，褪黑素处理 10 nM 时表达达到峰值。在 DPC 分化过程中，10 nM 褪黑素能显著诱导细胞内三磷酸腺苷（ATP）的增加，氧化型烟酰胺腺嘌呤二核苷酸（NAD+）/NADH 比值和活性氧（ROS）的减少。过氧化物酶体增殖物激活受体γ辅激活因子 1-α（PGC-1α）、核呼吸因子 1（NRF-1）和线粒体转录因子 A（TFAM）的 mRNA 和蛋白水平显著增加，在 10 nM 褪黑素处理的细胞中表达水平达到峰值。此外，DPC 分化过程中线粒体 DNA（mtDNA）拷贝数显著减少。
这些发现表明，褪黑素可以促进大鼠 DPC 的分化，并调节线粒体能量代谢、ROS 清除和线粒体生物发生。
