LIPUS promotes FOXO1 accumulation by downregulating miR-182 to enhance osteogenic differentiation in hPDLCs
LIPUS promotes FOXO1 accumulation by downregulating miR-182 to enhance osteogenic differentiation in hPDLCs
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LIPUS 通过下调 miR-182 促进 FOXO1 积累，增强 hPDLC 成骨分化
DOI：
10.1016/j.biochi.2019.08.005
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发表时间：
2019-10-01
期刊：
影响因子：
3.9
通讯作者：
Song, Jinlin
中科院分区：
文献类型：
--
作者：
Chen, Duanjing;Xiang, Mingli;Song, Jinlin
低强度脉冲超声（LIPUS）在临床治疗中促进骨折愈合。转录因子 Forkhead box O1 (FOXO1) 对于骨分化至关重要。但 FOXO1 是否参与 LIPUS 促进的骨分化尚不清楚。在目前的研究中，用 LIPUS 处理人原发性牙周膜细胞 (hPDLC) 促进了总 FOXO1 蛋白和细胞核 FOXO1 蛋白的积累。 LIPUS 诱导的 FOXO1 激活进一步导致碱性磷酸酶 (ALP) 和 runt 相关转录因子 2 (Runx2) 表达和基质矿化升高。 LIPUS 抑制 miR-182 表达，而 miR-182 通过转录后调节发挥 FOXO1 阻遏物的作用。 miR-182 的过度表达逆转了 LIPUS 增强的 FOXO1 表达和成骨分化。此外，LIPUS增强Akt磷酸化，通过诱导FOXO1核的细胞质易位来防止活性FOXO1过度积累。总之，我们的研究表明，FOXO1 作为 miR-182 的靶基因，在 LIPUS 促进的成骨分化中发挥着重要作用。这一新的分子见解揭示了 LIPUS 疗法在牙周骨缺损中的应用。 (C) 2019 Elsevier B.V. 和 Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM)。版权所有。
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. (C) 2019 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.