MiR-142-5p promotes bone repair by maintaining osteoblast activity

MiR-142-5p promotes bone repair by maintaining osteoblast activity
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MiR-142-5p 通过维持成骨细胞活性来促进骨修复。

DOI:
10.1007/s00774-016-0757-8
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发表时间:
2017-05-01
影响因子:
3.3
通讯作者:
Chen, Chao
Chen, Chao
中科院分区:
医学3区
文献类型:
--
作者:
Tu, Manli;Tang, Juanjuan;Chen, Chao

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microrna在调节骨再生和重塑中发挥重要作用。然而,microrna在骨修复中的病理生理作用尚不清楚。在这里,我们发现在骨愈合过程中miR-142-5p的显著上调与活跃的成骨细胞发生相关。在体外,miR-142-5p通过靶向编码含有www结构域的E3泛素蛋白连接酶1的基因,促进成骨细胞活性和基质矿化。我们还发现,miR-142-5p在老年小鼠的愈伤组织中的表达低于年轻小鼠的愈伤组织,这与年龄相关的骨愈合延迟直接相关。此外,在骨折区域用agomir-142-5p治疗可刺激成骨细胞活性,从而修复老年小鼠的骨折。因此,我们的研究揭示了miR-142-5p通过维持成骨细胞活性在骨折愈合中起着至关重要的作用,并为骨愈合提供了一种新的分子靶向治疗策略。
MicroRNAs play important roles in regulating bone regeneration and remodeling. However, the pathophysiological roles of microRNAs in bone repair remain unclear. Here we identify a significant upregulation of miR-142-5p correlated with active osteoblastogenesis during the bone healing process. In vitro, miR-142-5p promoted osteoblast activity and matrix mineralization by targeting the gene encoding WW-domain-containing E3 ubiquitin protein ligase 1. We also found that the expression of miR-142-5p in the callus of aged mice was lower than that in the callus of young mice and directly correlated with the age-related delay in bone healing. Furthermore, treatment with agomir-142-5p in the fracture areas stimulated osteoblast activity which repaired the bone fractures in aged mice. Thus, our study revealed that miR-142-5p plays a crucial role in healing fractures by maintaining osteoblast activity, and provided a new molecular target therapeutic strategy for bone healing.