■牙乳头细胞(DPC)是牙齿发育的关键干细胞之一,最终形成牙本质和牙髓。先前的研究已经报道PER2在体外DPC中以24小时振荡模式表达。在体内,PER2在成牙本质细胞(与DPC区分)中高度表达。然而,PER2是否调节DPC的牙源性分化尚不确定。本研究旨在研究PER2在DPCs牙源性分化中的作用,并初步探讨其作用机制。
■我们监测了体内分化的DPC中PER2的表达。我们使用PER2过表达和敲低研究来评估PER2在DPC分化中的作用,并进行细胞内ATP含量和活性氧(ROS)测定以进一步研究其机制。
■PER2的表达在整个DPC的体内牙本质分化过程中显著升高。过表达Per2提高了牙源性分化标志物的水平,如牙本质唾液酸糖蛋白(Dspp),牙本质基质蛋白1(Dmp1),和碱性磷酸酶(Alp),并增强了DPC中的矿化结节形成。相反,Per2的下调抑制了DPCs的分化。此外,下调Per2进一步影响DPC分化过程中细胞内ATP含量和ROS水平。
■总的来说,我们证明PER2正向调节DPCs的牙源性分化,其机制可能与线粒体功能有关,如细胞内ATP含量和ROS水平所示。
UNASSIGNED: Dental papilla cells (DPCs) are one of the key stem cells for tooth development, eventually forming dentin and pulp. Previous studies have reported that PER2 is expressed in a 24-hour oscillatory pattern in DPCs in vitro. In vivo, PER2 is highly expressed in odontoblasts (which are differentiated from DPCs). However, whether PER2 modulates the odontogenic differentiation of DPCs is uncertain. This research was to identify the function of PER2 in the odontogenic differentiation of DPCs and preliminarily explore its mechanisms.
UNASSIGNED: We monitored the expression of PER2 in DPCs differentiated in vivo. We used PER2 overexpression and knockdown studies to assess the role of PER2 in DPC differentiation and performed intracellular ATP content and reactive oxygen species (ROS) assays to further investigate the mechanism.
UNASSIGNED: PER2 expression was considerably elevated throughout the odontoblastic differentiation of DPCs in vivo. Overexpressing Per2 boosted levels of odontogenic differentiation markers, such as dentin sialophosphoprotein (Dspp), dentin matrix protein 1 (Dmp1), and alkaline phosphatase (Alp), and enhanced mineralized nodule formation in DPCs. Conversely, the downregulation of Per2 inhibited the differentiation of DPCs. Additionally, downregulating Per2 further affected intracellular ATP content and ROS levels during DPC differentiation.
UNASSIGNED: Overall, we demonstrated that PER2 positively regulates the odontogenic differentiation of DPCs, and the mechanism may be related to mitochondrial function as shown by intracellular ATP content and ROS levels.