LIPUS promotes FOXO1 accumulation by downregulating miR-182 to enhance osteogenic differentiation in hPDLCs

• Published in: Biochimie Vol. 165; pp. 219 - 228
• Main Authors: Chen, Duanjing, Xiang, Mingli, Gong, Yuanyuan, Xu, Ling, Zhang, Tingwei, He, Yao, Zhou, Mengjiao, Xin, Liangjing, Li, Jie, Song, Jinlin
• Format: Journal Article
• Language: English
• Published: France Elsevier B.V 01-10-2019
• Subjects: Cell Differentiation; Cells, Cultured; Forkhead Box Protein O1 - metabolism; FOXO1; Humans; Low intensity pulsed ultrasound; MicroRNAs - metabolism; miR-182; Osteogenesis - physiology; Osteogenic differentiation; Periodontal Ligament - cytology; Periodontal ligament cell; Ultrasonic Waves; miR-182; Periodontal ligament cell; Osteogenic differentiation; FOXO1; Low intensity pulsed ultrasound
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2019.08.005

Low intensity pulsed ultrasound (LIPUS) promotes bone fracture healing in clinical therapy. Transcription factor Forkhead box O1 (FOXO1) is crucial for bone differentiation. But whether FOXO1 is involved in LIPUS-promoted bone differentiation is largely unknown. In the current study, treatment of human primary periodontal ligament cells (hPDLCs) with LIPUS promoted total and nucleus FOXO1 protein accumulation. LIPUS-induced activation of FOXO1 further lead to higher alkaline phosphatase (ALP) and runt-related transcription factor 2 (Runx2) expression and matrix mineralization. LIPUS inhibited miR-182 expression, which functioned as a repressor of FOXO1 through post-transcriptional regulation. Overexpression of miR-182 reversed the LIPUS-enhanced FOXO1 expression and osteogenic differentiation. Moreover, LIPUS enhanced Akt phosphorylation, which functioned in preventing active FOXO1 excessive accumulation via inducing the cytoplasm translocation of nucleus FOXO1. In conclusion, our study revealed that FOXO1, which was a target gene of miR-182, played an essential role in LIPUS-promoted osteogenic differentiation. This new molecular insight throws light upon the application of LIPUS therapy on periodontal bone defect.
•LIPUS enhances osteogenic differentiation via promoting FOXO1 accumulation.•MiR-182 is a mechano-sensitive miRNA in hPDLCs.•FOXO1 is a target gene of miR-182 in hPDLCs.•LIPUS promotes FOXO1 accumulation by inhibiting miR-182.