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circRNA_0006393 通过海绵吸附 miR-145-5p 和上调 FOXO1 促进糖皮质激素诱导的骨质疏松症中的成骨作用。

circRNA_0006393 promotes osteogenesis in glucocorticoid‑induced osteoporosis by sponging miR‑145‑5p and upregulating FOXO1.

机构信息

Orthopedics Department, Gansu Provincial Hospital, Lanzhou, Gansu 730000, P.R. China.

Orthopedics Department, The Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250014, P.R. China.

出版信息

Mol Med Rep. 2019 Sep;20(3):2851-2858. doi: 10.3892/mmr.2019.10497. Epub 2019 Jul 12.

Abstract

Glucocorticoids are the most common cause of glucocorticoid‑induced osteoporosis (GIOP). Moreover, the role of circular RNAs (circRNAs) in the regulation of bone metabolism remains unclear. Therefore, in the present study, it was hypothesized that hsa_circ_0006393 may play an important role in GIOP. To investigate the role of circRNAs in GIOP, treatment with dexamethasone or transfection with a vector overexpressing hsa_circ_0006393 were performed using in vitro cell and in vivo mouse models. Reverse transcription‑quantitative PCR, fluorescence in situ hybridization and western blotting were performed to investigate the function of hsa_circ_0006393 in vitro. In addition, the effects of hsa_circ_0006393 on osteogenesis were investigated. Dual‑energy X‑ray absorptiometry analysis was performed to examine the osteogenic potential of hsa_circ_0006393 in vivo. Moreover, the mechanism underlying hsa_circ_0006393‑mediated bone metabolism regulation via the microRNA (miR)‑145‑5p/forkhead box O1 (FOXO1) pathway was investigated. The present results suggested that the expression level of hsa_circ_0006393 was decreased in patients with GIOP. Furthermore, the overexpression of hsa_circ_0006393 increased the expression level of genes associated with osteogenesis. Moreover, hsa_circ_0006393 was identified to be localized mainly in the cytoplasm and nucleus of bone marrow mesenchymal stem cells. miR‑145‑5p was found to be directly targeted by hsa_circ_0006393. Collectively, hsa_circ_0006393 increases the expression levels of osteogenic genes during bone remodeling by sponging miR‑145‑5p and upregulating FOXO1.

摘要

糖皮质激素是导致糖皮质激素诱导性骨质疏松症(GIOP)的最常见原因。此外,环状 RNA(circRNA)在骨代谢调节中的作用尚不清楚。因此,在本研究中,假设 hsa_circ_0006393 可能在 GIOP 中发挥重要作用。为了研究 circRNA 在 GIOP 中的作用,使用地塞米松处理或转染过表达 hsa_circ_0006393 的载体,建立体外细胞和体内小鼠模型。进行逆转录-定量 PCR、荧光原位杂交和 Western blot 分析,以研究 hsa_circ_0006393 在体外的功能。此外,还研究了 hsa_circ_0006393 对成骨的影响。双能 X 射线吸收仪分析用于研究 hsa_circ_0006393 在体内的成骨潜力。此外,还研究了 hsa_circ_0006393 通过 microRNA(miR)-145-5p/叉头框 O1(FOXO1)通路调节骨代谢的机制。本研究结果表明,GIOP 患者 hsa_circ_0006393 的表达水平降低。此外,hsa_circ_0006393 的过表达增加了与成骨相关的基因的表达水平。此外,hsa_circ_0006393 主要定位于骨髓间充质干细胞的细胞质和细胞核。miR-145-5p 被发现是 hsa_circ_0006393 的直接靶标。总之,hsa_circ_0006393 通过海绵吸附 miR-145-5p 和上调 FOXO1 增加骨重塑过程中成骨基因的表达水平。

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