Orthopedics Department, The 8th Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.
Department of Spine Surgery, Boxing People's Hospital, BinZhou, 256500, Shandong, China.
Biochem Biophys Res Commun. 2019 Aug 20;516(2):546-550. doi: 10.1016/j.bbrc.2019.06.087. Epub 2019 Jun 22.
Circular RNAs (circRNAs) are emerging as important regulators in human disease. The expression profile and mechanism of circRNAs in postmenopausal osteoporosis remains largely unknown. Bone morphogenetic protein 2 (BMP2) is known to play important role in inducing osteogenic differentiation. MiR-98 was reported to regulate osteogenic differentiation of human bone mesenchymal stromal cells by targeting BMP2.
We aimed to analyze circRNA expression profiles in osteoporosis and explore the molecular mechanism of circRNA_0016624 and interaction between circRNA_0016624, miR-98 and BMP2 during osteogenic differentiation.
RNA-seq and bioinformatics analysis was performed in postmenopausal osteoporosis patients to screen for differentially expressed circRNAs. MiRanda and TargetScan were used to detect miR-98 binding sites of circRNA_0016624 and the target relationship was confirmed by dual luciferase assay. Expression level of circRNA_0016624, miR-98 and BMP2 were measured by qRT-PCR or Western blot. ARS staining was used to observe the level of osteogenic differentiation after transfection.
There were 387 circRNAs were differentially expressed in osteoporosis (|fold change| > 2 and P-value < 0.01). circRNA_0016624 and BMP2 were down-regulated in osteoporosis. CircRNA_0016624 could sponge miR-98 and regulate miR-98 expression. Overexpression of circRNA_0016624 promoted the expression of BMP2 and prevented osteoporosis.
circRNA_0016624 could sponge miR-98 and enhance BMP2 expression, thus circRNA_0016624 prevents osteoporosis and may provide a novel therapeutic strategy.
环状 RNA（circRNAs）作为人类疾病中的重要调控因子而逐渐受到关注。然而，关于绝经后骨质疏松症中 circRNAs 的表达谱和作用机制仍知之甚少。骨形态发生蛋白 2（BMP2）已知在诱导成骨分化中发挥重要作用。有报道称，miR-98 通过靶向 BMP2 来调节人骨髓间充质干细胞的成骨分化。
本研究旨在分析骨质疏松症中的 circRNA 表达谱，并探讨 circRNA_0016624 在成骨分化过程中的分子机制，以及 circRNA_0016624、miR-98 和 BMP2 之间的相互作用。
对绝经后骨质疏松症患者进行 RNA-seq 和生物信息学分析，筛选差异表达的 circRNAs。利用 miRanda 和 TargetScan 预测 circRNA_0016624 与 miR-98 的结合位点，并通过双荧光素酶报告基因实验验证其靶关系。采用 qRT-PCR 或 Western blot 检测 circRNA_0016624、miR-98 和 BMP2 的表达水平。转染后通过碱性磷酸酶染色（ARS）观察成骨分化水平。
骨质疏松症患者中存在 387 个差异表达的 circRNAs（|fold change|>2，P 值<0.01）。circRNA_0016624 和 BMP2 在骨质疏松症中表达下调。circRNA_0016624 可与 miR-98 结合并调节其表达。circRNA_0016624 的过表达促进了 BMP2 的表达，并防止了骨质疏松症的发生。
circRNA_0016624 可以与 miR-98 结合并增强 BMP2 的表达，从而预防骨质疏松症，为骨质疏松症的治疗提供了新的策略。
