Department of Orthopaedics, Yichang Central People's Hospital, 183 Yiling Avenue, Wujiagang District, Yichang City, 443003, Hubei Province, P. R. China.
Department of Nuclear Medicine, Yichang Central People's Hospital, 183 Yiling Avenue, Wujiagang District, Yichang City, 443003, Hubei Province, P. R. China.
J Orthop Surg Res. 2021 Mar 3;16(1):170. doi: 10.1186/s13018-021-02323-7.
The dysregulation of circular RNAs (circRNAs) has been identified in various human diseases, including osteoarthritis (OA). The purpose of this study was to identify the role and mechanism of circ_SLC39A8 in regulating the progression of OA.
The expression levels of circ_SLC39A8, miR-591, and its potential target gene, interleukin-1-receptor-associated kinase 3 (IRAK3), were identified by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The relationship between miR-591 and circ_SLC39A8 or IRAK3 was predicted by bioinformatics tools and verified by dual-luciferase reporter.
Circ_SLC39A8 and IRAK3 were upregulated and miR-591 was downregulated in OA cartilage tissues. Knockdown of circ_SLC39A8 inhibited apoptosis and inflammation in OA chondrocytes, while these effects were reversed by downregulating miR-591. Promotion cell viability effects of miR-591 were partially reversed by IRAK3 overexpression.
Our findings indicated that knockdown of circ_SLC39A8 delayed the progression of OA via modulating the miR-591-IRAK3 axis, providing new insight into the molecular mechanisms of OA pathogenesis.
环状 RNA（circRNAs）的失调已在多种人类疾病中得到鉴定，包括骨关节炎（OA）。本研究的目的是鉴定 circ_SLC39A8 在调节 OA 进展中的作用和机制。
通过实时定量聚合酶链反应（qRT-PCR）鉴定 circ_SLC39A8、miR-591 及其潜在靶基因白细胞介素-1 受体相关激酶 3（IRAK3）的表达水平。通过细胞计数试剂盒-8（CCK-8）测定和流式细胞术分别测定细胞活力和凋亡。通过生物信息学工具预测 miR-591 与 circ_SLC39A8 或 IRAK3 之间的关系，并通过双荧光素酶报告实验验证。
OA 软骨组织中 circ_SLC39A8 和 IRAK3 上调，miR-591 下调。circ_SLC39A8 的敲低抑制 OA 软骨细胞的凋亡和炎症，而下调 miR-591 则逆转了这些作用。IRAK3 过表达部分逆转了 miR-591 促进细胞活力的作用。
我们的研究结果表明，circ_SLC39A8 的敲低通过调节 miR-591-IRAK3 轴延缓 OA 的进展，为 OA 发病机制的分子机制提供了新的见解。
