miRNA-29b improves bone healing in mouse fracture model
miRNA-29b improves bone healing in mouse fracture model
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DOI：
10.1016/j.mce.2016.04.014
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发表时间：
2016-07-15
影响因子：
4.1
通讯作者：
Li, Gang
中科院分区：
文献类型：
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作者：
Lee, Wayne Y.;Li, Nan;Li, Gang
许多 miRNA 调节骨重塑，它们在循环中的水平与骨折相关，但尚未显示 miRNA 可以直接改善骨折愈合。本研究旨在通过微泡超声系统进行位点特异性递送来研究 miR-29b-3p 对小鼠股骨骨折愈合的影响。定量实时聚合酶链反应 (qPCR) 和茜素红 S 染色表明，miR-29b-3p 促进小鼠骨髓来源的间充质干细胞的成骨。动物研究表明，骨折后第 2 周单次注射 miR-29b-3p 可以改善愈合结果，放射照相分析显示愈伤组织宽度和面积显着减小，而不会导致体重显着减轻。静态骨组织形态计量学分析显示miR-29b-3p增加了骨体积分数（BV/TV），显微计算机断层扫描（micro-CT）测量显示高密度骨的BV/TV和愈伤组织的骨矿物质密度（BMD）增加。三点弯曲机械测试显示相对刚度有所改善。然而，在第 2 周和第 3 周重复注射 miR-29b-3p 并没有产生额外的治疗效果，而是导致总组织体积增加和愈伤组织 BMD 降低。这是第一份通过微泡超声系统进行位点特异性递送显示 miR-29b-3p 对股骨骨折愈合具有显着治疗效果的报告。需要进一步的研究来调查潜在的机制并完善治疗方案。 (C) 2016 Elsevier Ireland Ltd. 保留所有权利。
A number of miRNAs regulates bone remodeling and their levels in circulation were associated with bone fracture, however no miRNAs have yet been shown to improve fracture healing directly. This study aimed to investigate the effect of miR-29b-3p on mice femoral fracture healing through site-specific delivery with microbubble-ultrasound system. miR-29b-3p promoted osteogenesis of mouse bone marrow derived mesenchymal stem cells as indicated with quantitative real-time polymerase chain reaction (qPCR) and Alizarin red S staining. Animal study showed that single injection of miR-29b-3p at week 2 post fracture improved healing outcome as indicated by significant decrease of callus width and area with radiographic analysis without causing significant weight loss. Static bone histomorphometry analysis showed that miR-29b-3p increased bone volume fraction (BV/TV), and micro-computed tomography (micro-CT) measurement showed increased BV/TV of high density bone and bone mineral density (BMD) of the callus. 3 point bending mechanical test showed improved relative stiffness. However, repeated injection of miR-29b-3p at weeks 2 and 3 did not result in additive therapeutic outcome, and caused increased total tissue volume and reduced BMD of the callus. This is the first report showing significant therapeutic effect of miR-29b-3p on femoral fracture healing through site-specific delivery with microbubble-ultrasound system. Further studies are warranted to investigate the underlying mechanisms and to refine the treatment protocol. (C) 2016 Elsevier Ireland Ltd. All rights reserved.