Long non-coding RNA, Bmcob, regulates osteoblastic differentiation of bone marrow mesenchymal stem cells
Long non-coding RNA, Bmcob, regulates osteoblastic differentiation of bone marrow mesenchymal stem cells
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长非编码RNA Bmcob调节骨髓间充质干细胞的成骨细胞分化
DOI：
10.1016/j.bbrc.2018.09.142
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发表时间：
2018-11-30
影响因子：
3.1
通讯作者：
Guo, Qi
中科院分区：
文献类型：
--
作者：
Sun, Xi;Yuan, Ying;Guo, Qi
骨髓间充质干细胞（BMSCs）的成骨分化障碍导致骨丢失。潜在的机制是复杂的，并没有完全理解。长链非编码RNA（longnon-codingRNA，lncRNA）是近年来发现的一种重要的骨代谢调控因子。在这里，我们发现了一种新的IncRNA，Bmcob，它调制原代小鼠BMSCs的成骨分化。在成骨细胞分化的早期至中期，Bmcob的表达水平显著上调。沉默Bmcob抑制体外BMSCs的成骨分化，而其过表达保护BMSCs免受氧化应激诱导的成骨抑制。随后，我们发现位于Bmcob基因旁边的硒蛋白P（Sepp 1）部分负责Bmcob的调节作用。此外，Bmcob基因敲低后，BMSCs中一系列硒蛋白表达下调。从机制上讲，我们发现Bmcob与硒代半胱氨酸插入序列结合蛋白2（SBP 2）相关，SBP 2是硒蛋白合成的关键反式作用因子。最后，我们提出了一个解释性的假设，即通过调节核质穿梭的SBP 2，Bmcob调节了一些硒蛋白的表达，包括sepp 1，然后介导的BMSCs的成骨。综上所述，我们的研究结果揭示了一种新的机制，调节BMSCs的成骨，并可能作为一个潜在的治疗骨质疏松症的目标。(C)2018爱思唯尔公司All rights reserved.
Disordered osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) contributes to bone loss. The underlying mechanisms are complicated and not fully understood. Long non-coding RNAs (lncRNAs) are emerging as an important regulatory factors on bone metabolism. Here, we discovered a novel IncRNA, Bmcob, which modulated osteogenic differentiation of primary mouse BMSCs. Expression levels of Bmcob were significantly upregulated in early-to-mid stages during osteoblast differentiation. Silencing of Bmcob suppressed osteoblastic differentiation of BMSCs in vitro, whereas its overexpression protected BMSCs from oxidative stress induced inhibition on osteogenesis. Subsequently, we discovered that selenoprotein P (Sepp1), which is located next to the Bmcob gene, was partly responsible for the regulatory effects of Bmcob. In addition, a series of selenoproteins were downregulated in BMSCs with Bmcob knockdown. Mechanistically, we found Bmcob was associated with selenocysteine insertion sequence binding protein 2 (SBP2), a critical trans-acting factor for selenoprotein synthesis. Finally, we suggest an explanatory hypothesis that through modulating nucleocytoplasmic shuttling of SBP2, Bmcob regulates a number of selenoproteins expression, including sepp1, and then mediates osteogenesis of BMSCs. Taken together, our results revealed a novel mechanism regulating osteogenesis of BMSCs and may function as a potential target for treating osteoporosis. (C) 2018 Elsevier Inc. All rights reserved.