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长链非编码 RNA 作为骨质疏松症骨髓干细胞的调控因子。

Long Noncoding RNAs as Bone Marrow Stem Cell Regulators in Osteoporosis.

机构信息

Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain.

Department of Traumatology and Orthopedic Surgery, Hospital UM Valdecilla, University of Cantabria-IDIVAL, Santander, Spain.

出版信息

DNA Cell Biol. 2020 Sep;39(9):1691-1699. doi: 10.1089/dna.2020.5672. Epub 2020 Jul 17.

Abstract

Long noncoding RNAs (lncRNAs) contribute toward regulating gene expression and cell differentiation and may be involved in the pathogenesis of several diseases. The objective of this study was to determine the expression patterns of lncRNAs in bone marrow mesenchymal stem cells (BMSCs) derived from patients with osteoporotic fractures and their relevance to osteogenic function. The BMSCs were isolated from the femoral head of patients with hip fractures (FRX) and controls with osteoarthritis (OA). We found 74 differentially expressed genes between FRX and OA, of which 33 were of the lncRNA type. Among them, 52 genes (20 lncRNAs) were replicated in another independent dataset. The differentially expressed lncRNAs were over-represented among those correlated with differentially expressed protein-coding genes. In addition, the comparison of pre- and post-differentiated paired samples revealed 163 differentially expressed genes, of which 99 were of the lncRNA type. Among them, the overexpression of induced an upregulation of typical osteoblastic genes. In conclusion, the analysis of lncRNA expression in BMSCs shows specific patterns in patients with osteoporotic fractures, as well as changes associated with osteogenic differentiation. The regulation of bone genes through lncRNAs might bring new opportunities for designing bone anabolic therapies in systemic and localized bone disorders.

摘要

长链非编码 RNA(lncRNA)在基因表达和细胞分化的调控中发挥作用,可能参与多种疾病的发病机制。本研究旨在确定骨质疏松性骨折患者骨髓间充质干细胞(BMSC)中 lncRNA 的表达模式及其与成骨功能的相关性。从髋部骨折(FRX)和骨关节炎(OA)患者的股骨头中分离出 BMSC。我们在 FRX 和 OA 之间发现了 74 个差异表达基因,其中 33 个是 lncRNA 类型。其中,另外一个独立数据集复制了 52 个基因(20 个 lncRNA)。差异表达的 lncRNA 在与差异表达的蛋白编码基因相关的基因中过表达。此外,对预分化和分化后配对样本的比较显示了 163 个差异表达基因,其中 99 个是 lncRNA 类型。其中,的过表达诱导典型成骨基因的上调。总之,BMSC 中 lncRNA 表达的分析显示出骨质疏松性骨折患者的特定模式,以及与成骨分化相关的变化。通过 lncRNA 调节骨基因可能为设计系统性和局部性骨疾病的骨合成治疗带来新的机会。

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