Department of Orthodontics, Affiliated Stomatological Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Mol Med Rep. 2018 Jan;17(1):1499-1506. doi: 10.3892/mmr.2017.8021. Epub 2017 Nov 10.
The present study aimed to investigate the expression and regulation of extracellular signal‑regulated kinase (ERK)1/2 and p38 mitogen‑activated protein kinase (MAPK) signaling pathways in periodontal tissue remodeling of orthodontic tooth movement. Sprague Dawley rats with orthodontic tooth movement were generated. After tension stress for 1, 3, 5, 7 and 14 days, the protein and mRNA expression levels of ERK1/2 and p38 in periodontal tissue were determined by western blotting and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), respectively. Primary human periodontal ligament cells (hPDLCs) were separated and characterized. Following exposure to centrifugal force for 1, 2, 6, 8 and 12 h, the protein expression levels of ERK1/2 and p38 MAPK, and the mRNA expression levels of ERK1/2, p38 and osteogenesis associated‑genes [including alkaline phosphatase (ALP), osteopontin (OPN), collagen I (Col I), osteocalcin (OCN) and bone sialoprotein (BSP)] were measured. The protein expression levels of ERK1/2 and p38 MAPK in periodontal tissue and hPDLCs treated with stress were similar to those in the control groups. However, compared with the control, the phosphorylation and mRNA expression levels of the genes encoding ERK1/2 and p38 MAPK in orthodontic periodontal tissue and forced hPDLCs were elevated. These increases reached a peak at 5 days for orthodontic periodontal tissue and at 6 h for forced hPDLCs. In forced hPDLCs, the mRNA expression levels of ALP, OPN, Col I, OCN and BSP were notably and continuously upregulated in a time‑dependent manner. In addition, hPDLCs were treated with the ERK1/2 inhibitor, PD098059, and the p38 MAPK inhibitor, SB203580, and the mRNA expression levels of the osteogenesis associated‑genes were then measured using RT‑qPCR. Following treatment with the ERK1/2 inhibitor and p38 MAPK inhibitor, the mRNA expression levels of ALP, OPN, Col I, OCN and BSP were significantly downregulated. In conclusion, ERK1/2 and p38 MAPK signaling pathways may be positively and closely associated with periodontal tissue remodeling of orthodontic tooth movement.
本研究旨在探讨细胞外信号调节激酶（ERK）1/2 和 p38 丝裂原活化蛋白激酶（MAPK）信号通路在正畸牙齿移动牙周组织重塑中的表达和调节。建立正畸牙齿移动的 Sprague Dawley 大鼠模型。在张力刺激 1、3、5、7 和 14 天后，通过 Western blot 和逆转录-定量聚合酶链反应（RT-qPCR）分别测定牙周组织中 ERK1/2 和 p38 的蛋白和 mRNA 表达水平。分离并鉴定原代人牙周韧带细胞（hPDLCs）。在暴露于离心力 1、2、6、8 和 12 h 后，测定 ERK1/2 和 p38 MAPK 的蛋白表达水平，以及 ERK1/2、p38 和骨形成相关基因[包括碱性磷酸酶（ALP）、骨桥蛋白（OPN）、I 型胶原（Col I）、骨钙素（OCN）和骨涎蛋白（BSP）]的 mRNA 表达水平。与对照组相比，牙周组织和应激处理的 hPDLCs 中 ERK1/2 和 p38 MAPK 的蛋白表达水平相似。然而，与对照组相比，正畸牙周组织和强制 hPDLCs 中编码 ERK1/2 和 p38 MAPK 的基因的磷酸化和 mRNA 表达水平升高。这些增加在正畸牙周组织中于第 5 天达到峰值，在强制 hPDLCs 中于第 6 小时达到峰值。在强制 hPDLCs 中，ALP、OPN、Col I、OCN 和 BSP 的 mRNA 表达水平呈时间依赖性显著上调。此外，用 ERK1/2 抑制剂 PD098059 和 p38 MAPK 抑制剂 SB203580 处理 hPDLCs，然后使用 RT-qPCR 测定骨形成相关基因的 mRNA 表达水平。用 ERK1/2 抑制剂和 p38 MAPK 抑制剂处理后，ALP、OPN、Col I、OCN 和 BSP 的 mRNA 表达水平显著下调。综上所述，ERK1/2 和 p38 MAPK 信号通路可能与正畸牙齿移动的牙周组织重塑呈正相关且密切相关。
