MiR-27a targets DKK2 and SFRP1 to promote reosseointegration in the regenerative treatment of peri-implantitis
MiR-27a targets DKK2 and SFRP1 to promote reosseointegration in the regenerative treatment of peri-implantitis
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MiR-27a 靶向 DKK2 和 SFRP1 以促进种植体周围炎再生治疗中的骨整合
DOI：
10.1002/jbmr.3575
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发表时间：
2019-01-01
影响因子：
6.2
通讯作者：
Huang, Hui
中科院分区：
文献类型：
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作者：
Wu, Xiaolin;Gu, Qinhua;Huang, Hui
在种植体周围炎的发炎微环境中，种植体表面上有限的骨生成阻碍了使用当前临床疗法的良好的骨整合。microRNA（miRNAs）作为一种有效的分子管理者，可以同时调控多种内源性过程，如炎症和骨生成。miRNA的递送可能提供有效治疗某些疾病的方法。在这项研究中，我们发现miR-27 a在犬种植体周围炎模型的样本中差异性下调。我们发现，过表达miR-27 a通过改善TNF-α对体外骨形成的抑制，积极调节成骨-血管生成偶联。从机制上讲，我们将Dickkopf 2（DKK 2）和分泌型卷曲相关蛋白1（SFRP 1）确定为两个重要的直接miR-27 a靶点，它们具有成骨和血管生成作用。此外，我们构建了miR-27 a增强的递送系统，以修复犬种植体周围炎模型中种植体周围的骨缺损。结果表明，miR-27 a处理组可以优化体内新骨形成和再骨整合。我们的试验提供了证据表明，这种策略对种植体周围炎具有治疗效果，表明它代表了一种可行的方法来保持牙种植体的稳定性和咀嚼功能。(c)2018年美国骨与矿物质研究学会。
In the inflamed microenvironment of peri-implantitis, limited osteogenesis on the implant surface impedes well-established reosseointegration using current clinical therapies. MicroRNAs (miRNAs) function as potent molecular managers that may simultaneously regulate multiple endogenous processes such as inflammation and osteogenesis. The delivery of miRNAs may provide a way to effectively treat some diseases. In this study, we showed that miR-27a was differentially downregulated in samples from a canine peri-implantitis model. We found that overexpressing miR-27a positively regulated osteogenesis-angiogenesis coupling by ameliorating the TNF-alpha inhibition of bone formation in vitro. Mechanistically, we identified Dickkopf2 (DKK2) and secreted frizzled related protein 1 (SFRP1) as two essential direct miR-27a targets that were osteogenic and angiogenic. Furthermore, we constructed a miR-27a-enhanced delivery system to repair the bone defect around implants in a canine peri-implantitis model. The results demonstrated that the miR-27a-treated group could optimize new bone formation and reosseointegration in vivo. Our assay provides evidence that this strategy exerts therapeutic effects on peri-implantitis, suggesting that it represents a feasible method to maintain the stability and masticatory function of dental implants. (c) 2018 American Society for Bone and Mineral Research.