AC-l-亮氨酸-聚乙烯亚胺介导的miR-34a递送可改善正畸力作用下的成骨分化。

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

作者信息

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

机构信息

Department of Orthodontics, School and Hospital of Stomatology, Jilin University, Changchun 130021, China.

Department of Periodontics, School and Hospital of Stomatology, Jilin University, Changchun 130021, China.

出版信息

Oncotarget. 2017 Nov 30;8(66):110460-110473. doi: 10.18632/oncotarget.22790. eCollection 2017 Dec 15.

Rare therapeutic genes or agents are reported to control orthodontic bone remodeling. MicroRNAs have recently been associated with bone metabolism. Here, we report the and effects of miR-34a on osteogenic differentiation under orthodontic force using an -acetyl-L-leucine-modified polyethylenimine (-Ac-l-Leu-PEI) carrier. -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 and , Runx2 and ColI protein levels, and early osteogenesis function under orthodontic strain . MiR-34a also enhanced alveolar bone remodeling under orthodontic force , 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 -Ac-l-Leu-PEI could be a potential therapeutic target for orthodontic treatment.

据报道，罕见的治疗性基因或药物可控制正畸骨重塑。微小RNA最近被发现与骨代谢有关。在此，我们报告了使用N-乙酰-L-亮氨酸修饰的聚乙烯亚胺（N-Ac-l-Leu-PEI）载体时，miR-34a在正畸力作用下对成骨分化的促进和影响。N-Ac-l-Leu-PEI在大鼠骨矿干细胞和局部牙槽骨组织中表现出低细胞毒性和高miR-34a转染效率。转染后，miR-34a增强了正畸应变下大鼠骨矿干细胞和人牙周膜细胞的成骨分化、Runx2和ColI蛋白水平以及早期成骨功能。miR-34a还增强了正畸力作用下的牙槽骨重塑，表现为基因和蛋白表达升高、牙槽骨合成代谢指标上调以及牙齿移动减少。我们确定，正畸力作用下miR-34a促进成骨的机制可能与GSK-3β有关。这些结果表明，由N-Ac-l-Leu-PEI递送的miR-34a可能是正畸治疗的潜在治疗靶点。