甲状旁腺激素的间歇性给药通过JNK和P38丝裂原活化蛋白激酶途径增强根尖乳头干细胞的成牙/成骨分化。
Intermittent Administration of Parathyroid Hormone Enhances Odonto/Osteogenic Differentiation of Stem Cells from the Apical Papilla via JNK and P38 MAPK Pathways.
作者信息
Pang Xiyao, Zhuang Ying, Li Zehan, Jing Shuanglin, Cai Qin, Zhang Fengge, Xue Changao, Yu Jinhua
机构信息
Department of Stomatology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Endodontic Department, School of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, China.
出版信息
Stem Cells Int. 2020 Feb 14;2020:5128128. doi: 10.1155/2020/5128128. eCollection 2020.
OBJECTIVE
Parathyroid hormone (PTH) is considered to be essential during the tooth development. Stem cells from the apical papilla (SCAPs) are responsible for dentine formation. However, the interaction between PTH and SCAPs remains unclear. This study was aimed at investigating the effects of PTH on odonto/osteogenic differentiation capacity of SCAPs and elucidating the underlying molecular mechanisms. . Here, SCAPs were isolated and identified . Effects of PTH on the proliferation of SCAPs were determined by Cell Counting Kit-8 (CCK-8), flow cytometry (FCM), and EdU. Alkaline phosphatase (ALP) activity, alizarin red staining, Western blot, and RT-PCR were carried out to detect the odonto/osteogenic differentiation of PTH-treated SCAPs as well as the participation of the MAPK signaling pathway.
RESULTS
An ALP activity assay determined that 10 mol/L PTH was the optimal concentration for the induction of SCAPs with no significant influence on the proliferation of SCAPs as indicated by CCK-8, FCM, and EdU. The expression of odonto/osteogenic markers was significantly upregulated in mRNA levels and protein levels. Moreover, intermittent treatment of PTH also increased phosphorylation of JNK and P38, and the differentiation was suppressed following the inhibition of JNK and P38 MAPK pathways.
CONCLUSION
PTH can regulate the odonto/osteogenic differentiation of SCAPs via JNK and P38 MAPK pathways.
目的
甲状旁腺激素(PTH)被认为在牙齿发育过程中至关重要。根尖乳头干细胞(SCAPs)负责牙本质形成。然而,PTH与SCAPs之间的相互作用仍不清楚。本研究旨在探讨PTH对SCAPs牙本质/成骨分化能力的影响,并阐明其潜在的分子机制。在此,分离并鉴定了SCAPs。采用细胞计数试剂盒-8(CCK-8)、流式细胞术(FCM)和EdU检测PTH对SCAPs增殖的影响。进行碱性磷酸酶(ALP)活性检测、茜素红染色、蛋白质印迹法和逆转录-聚合酶链反应(RT-PCR),以检测PTH处理的SCAPs的牙本质/成骨分化以及丝裂原活化蛋白激酶(MAPK)信号通路的参与情况。
结果
碱性磷酸酶活性检测确定10μmol/L PTH是诱导SCAPs的最佳浓度,CCK-8、FCM和EdU结果表明其对SCAPs的增殖无显著影响。牙本质/成骨标志物的表达在mRNA水平和蛋白质水平均显著上调。此外,PTH的间歇处理还增加了JNK和P38的磷酸化,抑制JNK和P38 MAPK通路后分化受到抑制。
结论
PTH可通过JNK和P38 MAPK通路调节SCAPs的牙本质/成骨分化。