Waki T, Lee S Y, Niikura T, Iwakura T, Dogaki Y, Okumachi E, Kuroda R, Kurosaka M
Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Bone Joint J. 2015 Aug;97-B(8):1144-51. doi: 10.1302/0301-620X.97B8.34966.
MicroRNAs (miRNAs ) are small non-coding RNAs that regulate gene expression. We hypothesised that the functions of certain miRNAs and changes to their patterns of expression may be crucial in the pathogenesis of nonunion. Healing fractures and atrophic nonunions produced by periosteal cauterisation were created in the femora of 94 rats, with 1:1 group allocation. At post-fracture days three, seven, ten, 14, 21 and 28, miRNAs were extracted from the newly generated tissue at the fracture site. Microarray and real-time polymerase chain reaction (PCR) analyses of day 14 samples revealed that five miRNAs, miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p, were highly upregulated in nonunion. Real-time PCR analysis further revealed that, in nonunion, the expression levels of all five of these miRNAs peaked on day 14 and declined thereafter. Our results suggest that miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p may play an important role in the development of nonunion. These findings add to the understanding of the molecular mechanism for nonunion formation and may lead to the development of novel therapeutic strategies for its treatment.
微小RNA（miRNA）是一类调控基因表达的小型非编码RNA。我们推测某些miRNA的功能及其表达模式的变化可能在骨不连的发病机制中起关键作用。在94只大鼠的股骨上制造愈合性骨折以及骨膜烧灼所致的萎缩性骨不连，并按1:1的比例进行分组。在骨折后的第3、7、10、14、21和28天，从骨折部位新生成的组织中提取miRNA。对第14天样本进行的微阵列和实时聚合酶链反应（PCR）分析显示，5种miRNA，即miR-31a-3p、miR-31a-5p、miR-146a-5p、miR-146b-5p和miR-223-3p，在骨不连中高度上调。实时PCR分析进一步显示，在骨不连中，这5种miRNA的表达水平均在第14天达到峰值，随后下降。我们的结果表明，miR-31a-3p、miR-31a-5p、miR-146a-5p、miR-146b-5p和miR-223-3p可能在骨不连的发生发展中起重要作用。这些发现增进了对骨不连形成分子机制的理解，并可能为其治疗带来新的治疗策略的发展。
