N-AC-l-Leu-PEI-mediated miR-34a delivery improves osteogenic differentiation under orthodontic force

N-AC-l-Leu-PEI 介导的 miR-34a 递送可改善正畸力下的成骨分化

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作者:Wenwen Yu, Yi Zheng, Zhujun Yang, Hongbo Fei, Yang Wang, Xu Hou, Xinhua Sun, Yuqin Shen

Abstract

Rare therapeutic genes or agents are reported to control orthodontic bone remodeling. MicroRNAs have recently been associated with bone metabolism. Here, we report the in vitro and in vivo effects of miR-34a on osteogenic differentiation under orthodontic force using an N-acetyl-L-leucine-modified polyethylenimine (N-Ac-l-Leu-PEI) carrier. N-Ac-l-Leu-PEI exhibited low cytotoxicity and high miR-34a transfection efficiency in rat bone mineral stem cells and local alveolar bone tissue. After transfection, miR-34a enhanced the osteogenic differentiation of Runx2 and ColI, Runx2 and ColI protein levels, and early osteogenesis function under orthodontic strain in vitro. MiR-34a also enhanced alveolar bone remodeling under orthodontic force in vivo, as evidenced by elevated gene and protein expression, upregulated indices of alveolar bone anabolism, and diminished tooth movement. We determined that the mechanism miR-34a in osteogenesis under orthodontic force may be associated with GSK-3β. These results suggested that miR-34a delivered by N-Ac-l-Leu-PEI could be a potential therapeutic target for orthodontic treatment.

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