The microRNA-10a/ID3/RUNX2 axis modulates the development of Ossification of Posterior Longitudinal Ligament.
The microRNA-10a/ID3/RUNX2 axis modulates the development of Ossification of Posterior Longitudinal Ligament.
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microRNA-10a/ID3/RUNX2轴调节后纵韧带骨化的发展
DOI：
10.1038/s41598-018-27514-x
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发表时间：
2018-06-15
影响因子：
4.6
通讯作者：
Yuan W
中科院分区：
文献类型：
--
作者：
Xu C;Zhang H;Gu W;Wu H;Chen Y;Zhou W;Sun B;Shen X;Zhang Z;Wang Y;Liu Y;Yuan W
后纵韧带骨化是脊柱韧带的病理性异位骨化。然而，其潜在的分子机制仍不清楚。我们以前的研究结果表明，改变microRNA调控网络是OPLL的发展至关重要。在这里，我们开始揭示这些改变的OPLL特异性microRNA的详细机制。我们从先前的测序数据中筛选了一组差异表达的OPLL特异性microRNA，并显示microRNA-10a在体外积极调节后韧带细胞的骨化。使用从4周龄BALB/c纯合子裸鼠中生长的组织工程支架，我们发现后韧带细胞中microRNA-10a表达的改变确实影响了体内异位骨形成。此外，计算分析表明，负性骨化调节因子ID 3是microRNA-10a的功能靶基因，其表达在microRNA-10a体外和体内调控过程中也发生了显著变化。此外，我们已经证明microRNA-10a的骨化促进功能需要ID 3，因为ID 3积极抑制RUNX 2。因此，我们确定了高度改变的OPLL特异性microRNA-10a通过调节ID 3/RUNX 2轴在调节OPLL发展中的关键作用。
Ossification of the posterior longitudinal ligament (OPLL) presents as pathological heterotopic ossification of the spinal ligaments. However, its underlying molecular mechanism is still unclear. Our previous findings suggested that altered microRNA regulatory network are critical for the development of OPLL. Here, we set out to unveiling the detailed mechanism of those altered OPLL-specific microRNAs. We screened a set of differentially expressed OPLL-specific microRNAs from the previous sequencing data and showed that microRNA-10a actively modulates the ossification of posterior ligament cellsin vitro. Using a tissue-engineered scaffold grown from 4-week-old BALB/c homozygous nude mice, we found that altered microRNA-10a expression in posterior ligament cells indeed affected the heterotopic bone formationin vivo. Furthermore, computational analysis showed that the negative ossification regulator ID3 is a functional target gene of microRNA-10a, and its expression was also significantly altered during microRNA-10a modulation bothin vitroandin vivo. Also, we have demonstrated that the ossification promoting function of microRNA-10a requires ID3, as ID3 actively inhibits RUNX2. Thus, we identified a critical role for highly altered OPLL-specific microRNA-10a in regulating the development of OPLL by modulating the ID3/RUNX2 axis.
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影响因子：
3.7
作者：
Jia H;Zhang Z;Zou D;Wang B;Yan Y;Luo M;Dong L;Yin H;Gong B;Li Z;Wang F;Song W;Liu C;Ma Y;Zhang J;Zhao H;Li J;Yu J
通讯作者：
Yu J
影响因子：
6
作者：
Chambers, RC;Leoni, P;Heller, RA
通讯作者：
Heller, RA
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0.4
作者：
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作者：
Stadthagen G;Tehler D;Høyland-Kroghsbo NM;Wen J;Krogh A;Jensen KT;Santoni-Rugiu E;Engelholm LH;Lund AH
通讯作者：
Lund AH
影响因子：
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作者：
Li, Jun;Zhang, Yongqing;He, Xijing
通讯作者：
He, Xijing