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

Wang,Xing‑Bo; Li,Peng‑Biao; Guo,Shi‑Fang; Yang,Qing‑Shan; Chen,Zhi‑Xin; Wang,Dachuan; Shi,Song‑Bo

doi:10.3892/mmr.2019.10497

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

Authors:
- Xing‑Bo Wang
- Peng‑Biao Li
- Shi‑Fang Guo
- Qing‑Shan Yang
- Zhi‑Xin Chen
- Dachuan Wang
- Song‑Bo Shi
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Affiliations: 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
Published online on: July 12, 2019 https://doi.org/10.3892/mmr.2019.10497
Pages: 2851-2858

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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.

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