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环状RNA-0076906和环状RNA-0134944的失调与中国汉族绝经后女性骨质疏松症及骨质疏松性骨折易感性相关。

Dysregulation of circRNA-0076906 and circRNA-0134944 is Correlated with Susceptibility to Osteoporosis and Osteoporotic Fracture in Postmenopausal Females from the Chinese Han Population.

作者信息

Yang Weijie, Zhang Wei, Li Fengqian, Xu Ning, Sun Ping

机构信息

Department of Orthopedics, Shanghai Eighth People's Hospital, Shanghai, 200235, People's Republic of China.

出版信息

Pharmgenomics Pers Med. 2023 Mar 10;16:183-194. doi: 10.2147/PGPM.S394757. eCollection 2023.

DOI:10.2147/PGPM.S394757
PMID:36926413
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10013579/
Abstract

INTRODUCTION

Many circRNAs, such as circRNA-0076906 and circRNA-0134944, have been reported to participate in the pathogenesis of osteoporosis via sponging miRNAs in postmenopausal female patients. In this study, we aimed to study potential signaling pathways underlying the role of certain circRNAs, miRNAs and their target genes in the pathogenesis of osteoporotic fracture in postmenopausal females.

METHODS

Quantitative real-time PCR was performed to analyze the expression of circRNAs, miRNAs and their targets genes. Luciferase assays were carried out to explore the regulatory relationship between circ_0076906/miR-548i/OGN and circ_0134944/miR-630/TLR4.

RESULTS

Osteoporosis and fracture were positively correlated to the expression of circ_0134944, miR-548i and TLR4, but negatively correlated to the expression of circ_0076906, miR-630 and OGN in the peripheral blood and bone tissue samples of postmenopausal women. Luciferase activities of wild-type circ_0076906 and OGN were inhibited by miR-548i, and the luciferase activities of wild-type circ_0134944 and TLR4 were suppressed by miR-630 in MG-63 and U-2 OS cells. Inhibition of circ_0076906 expression in MG-63 and U-2 OS cells activated the expression of miR-548i and inhibited the expression of OGN. Moreover, the overexpression of circ_0134944 in MG-63 and U-2 OS cells suppressed the expression of miR-630 and enhanced the expression of TLR4.

CONCLUSION

This study implied that the dysregulation of circRNA-0076906 and circRNA-0134944 modulated their specific signaling and thus contributed to the severity of osteoporosis, increasing the risk of osteoporotic fracture.

摘要

引言

许多环状RNA,如circRNA - 0076906和circRNA - 0134944,已被报道在绝经后女性患者中通过吸附微小RNA参与骨质疏松症的发病机制。在本研究中,我们旨在研究某些环状RNA、微小RNA及其靶基因在绝经后女性骨质疏松性骨折发病机制中潜在的信号通路。

方法

采用定量实时PCR分析环状RNA、微小RNA及其靶基因的表达。进行荧光素酶报告基因检测以探究circ_0076906/miR - 548i/OGN和circ_0134944/miR - 630/TLR4之间的调控关系。

结果

骨质疏松症和骨折与绝经后女性外周血和骨组织样本中circ_0134944、miR - 548i和TLR4的表达呈正相关,但与circ_0076906、miR - 630和OGN的表达呈负相关。在MG - 63和U - 2 OS细胞中,miR - 548i抑制野生型circ_0076906和OGN的荧光素酶活性,miR - 630抑制野生型circ_0134944和TLR4的荧光素酶活性。在MG - 63和U - 2 OS细胞中抑制circ_0076906的表达可激活miR - 548i的表达并抑制OGN的表达。此外,在MG - 63和U - 2 OS细胞中过表达circ_0134944可抑制miR - 630的表达并增强TLR4的表达。

结论

本研究表明,circRNA - 0076906和circRNA - 0134944的失调调节了它们的特定信号通路,从而导致骨质疏松症的严重程度增加,增加了骨质疏松性骨折的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8d6/10013579/0a8eac963750/PGPM-16-183-g0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8d6/10013579/7b7fe32976ba/PGPM-16-183-g0001.jpg
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