High-glucose-induced miR-214-3p inhibits BMSCs osteogenic differentiation in type 1 diabetes mellitus
High-glucose-induced miR-214-3p inhibits BMSCs osteogenic differentiation in type 1 diabetes mellitus
复制标题
高糖诱导的 miR-214-3p 抑制 1 型糖尿病中 BMSC 成骨分化
DOI：
10.1038/s41420-019-0223-1
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发表时间：
2019-11-12
影响因子：
7
通讯作者：
Wang, Xiaogang
中科院分区：
文献类型：
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作者：
Wang, Rongze;Zhang, Yuanxu;Wang, Xiaogang
1型糖尿病（T1 DM）是一种自身免疫性胰岛素依赖性疾病，与破坏骨稳态有关。越来越多的证据证明miRNAs广泛参与了骨稳态的调节。然而，miRNAs是否也调节T1 DM小鼠骨髓间充质干细胞（BMSCs）的成骨分化仍在探索中。本研究利用miRNA芯片筛选差异表达的miRNA，发现miR-214- 3 p可能抑制T1 DM小鼠BMSCs成骨分化。我们发现高糖抑制了BMSCs的成骨分化，并显著升高了miR-214- 3 p的表达。进一步研究发现，在高糖条件下，AgomiR-214- 3 p抑制BMSCs的成骨分化，而AntagomiR-214- 3 p促进BMSCs的成骨分化。此外，我们发现miR-214- 3 p敲除T1 DM小鼠对高糖诱导的骨丢失具有抗性。这些结果为高糖诱导的miR-214- 3 p在体外和体内BMSCs成骨分化中的抑制作用提供了新的见解。分子生物学研究表明，miR-214- 3 p通过靶向β-catenin的3′-UTR抑制BMSCs的成骨分化，这一点在人骨标本和T1 DM患者BMSCs中得到进一步证实。综上所述，我们的研究发现miR-214- 3 p是T1 DM小鼠BMSCs成骨分化的关键调节因子。我们的研究结果还表明，miR-214- 3 p可能是治疗T1 DM患者骨疾病的潜在靶点。
Type 1 diabetes mellitus (T1DM) is an autoimmune insulin-dependent disease associated with destructive bone homeostasis. Accumulating evidence has proven that miRNAs are widely involved in the regulation of bone homeostasis. However, whether miRNAs also regulate osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in T1DM mice is under exploration. In this study, miRNA microarray was utilized to screen the differentially expressed miRNAs, which uncovered that miR-214-3p potentially inhibited BMSCs osteogenic differentiation in T1DM mice. We found that high glucose suppressed BMSCs osteogenic differentiation with significant elevation of the miR-214-3p expression. Further study found that the osteogenic differentiation of BMSCs was inhibited by AgomiR-214-3p while enhanced by AntagomiR-214-3p in BMSCs supplemented with high glucose. Moreover, we found that miR-214-3p knockout T1DM mice were resistant to high-glucose-induced bone loss. These results provide a novel insight into an inhibitory role of high-glucose-induced miR-214-3p in BMSCs osteogenic differentiation both in vitro and in vivo. Molecular studies revealed that miR-214-3p inhibits BMSCs osteogenic differentiation by targeting the 3′-UTR of β-catenin, which was further corroborated in human bone specimens and BMSCs of T1DM patients. Taken together, our study discovered that miR-214-3p is a pivotal regulator of BMSCs osteogenic differentiation in T1DM mice. Our findings also suggest that miR-214-3p could be a potential target in the treatment of bone disorders in patients with T1DM.