Expression and regulation of the ERK1/2 and p38 MAPK signaling pathways in periodontal tissue remodeling of orthodontic tooth movement.

Abstract

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.