Gu Huijie, Wu Liang, Chen Haihong, Huang Zhongyue, Xu Jun, Zhou Kaifeng, Zhang Yiming, Chen Jiong, Xia Jiangni, Yin Xiaofan
Department of Orthopedics, Minhang Hospital, Fudan University Shanghai 201199, China.
Am J Transl Res. 2019 May 15;11(5):2940-2954. eCollection 2019.
This study aimed to identify specific microRNAs (miRNAs) related to postmenopausal osteoporosis (OP) in human. A total of 67 conserved miRNAs, including 50 miRNAs significantly up-regulated and 17 miRNAs significantly downregulated, showed differential expression between OP group and control group. 180 hairpin structures were predicted and 199 potential novel miRNA candidates with 18 to 25 nt in length, which will greatly enrich the human miRBase. 4 miRNAs (miR-518b, miR-582-3p, miR-148a-3p and miRNA-223-3p) had upregulated expression and 4 (miR-7d-5p, miR-210-3p, miR-324-5p and miR-654-3p) showed down-regulated expression. Target genes of these miRNAs were involved in bone development, cell proliferation in bone marrow, osteoblast development, negative regulation of osteoblast differentiation, and negative regulation of osteoclast development, as well as several osteogenesis related pathways. Canonical Wnt signaling pathway was selected for verification and function analysis. The expression of Wnt1, FZD10, LRP5, DVL2 and LEF1 was down-regulated significantly, while that of SFRP1, DKK1, and CHD8 was up-regulated markedly. In conclusion, these genes play important roles in OP, which improves our understanding of pathogenesis of OP.
本研究旨在鉴定与人类绝经后骨质疏松症(OP)相关的特定微小RNA(miRNA)。共有67个保守的miRNA,包括50个显著上调的miRNA和17个显著下调的miRNA,在OP组和对照组之间表现出差异表达。预测了180个发夹结构,并发现了199个长度为18至25个核苷酸的潜在新型miRNA候选物,这将极大地丰富人类miRBase。4个miRNA(miR-518b、miR-582-3p、miR-148a-3p和miRNA-223-3p)表达上调,4个(miR-7d-5p、miR-210-3p、miR-324-5p和miR-654-3p)表达下调。这些miRNA的靶基因参与骨发育、骨髓细胞增殖、成骨细胞发育、成骨细胞分化的负调控、破骨细胞发育的负调控以及几条与骨生成相关的途径。选择经典Wnt信号通路进行验证和功能分析。Wnt1、FZD10、LRP5、DVL2和LEF1的表达显著下调,而SFRP1、DKK1和CHD8的表达显著上调。总之,这些基因在OP中起重要作用,这增进了我们对OP发病机制的理解。