Joint Surgery and Sport Medicine Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, People's Republic of China.
Kaohsiung J Med Sci. 2022 Dec;38(12):1168-1177. doi: 10.1002/kjm2.12604. Epub 2022 Oct 24.
Osteoarthritis (OA) is a chronic degenerative joint disease and is the most prevalent and disabling form of arthritis worldwide. Autophagy plays a vital role in OA. This study aimed to explore whether covalently closed circular RNA MSR (circRNA-MSR) could affect the F-box Only Protein 21 (FBXO21) expression by targeting microRNA-761 (miR-761), thereby affecting the autophagy in OA chondrocytes. Clinical OA tissues were collected, and circRNA-MSR, miR-761, and FBXO21 expressions were detected via quantitative real-time polymerase chain reaction (qRT-PCR). An in vitro OA model was constructed by treating C28/I2 cells with LPS and treating them with overexpression or knockdown vector of circRNA-MSR, miR-761, and FBXO21, and autophagy inhibitor 3-MA. Fluorescence in situ hybridization (FISH) determined the location of circRNA-MSR and miR-761. Dual-luciferase assay assessed circRNA-MSR and miR-761, along with the bindings of miR-761 and FBXO21. Cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. LC3 II/I, p62 and beclin 1 expressions were detected via the western blot. circRNA-MSR and FBXO21 levels were elevated in OA, but miR-761 level was inhibited. Suppressing circRNA-MSR promoted the autophagy of LPS-treated cells. circRNA-MSR could bind to miR-761 and inhibit its expression. MiR-761 inhibition reversed the promoted autophagy caused by circRNA-MSR knockdown in LPS-treated C28/I2 cells. Moreover, miR-761 could target FBXO21 and inhibit its expression. FBXO21 overexpression reversed the increased autophagy caused by miR-761 overexpression in LPS-treated C28/I2 cells. circRNA-MSR could affect FBXO21 level via targeting miR-761, thereby repressing autophagy in OA chondrocytes, providing a new target and strategy for OA treatment.
骨关节炎（OA）是一种慢性退行性关节疾病，是全球最普遍和致残性的关节炎形式。自噬在 OA 中起着至关重要的作用。本研究旨在探讨环状 RNA MSR（circRNA-MSR）是否可以通过靶向 microRNA-761（miR-761）来影响 F-box 仅蛋白 21（FBXO21）的表达，从而影响 OA 软骨细胞的自噬。通过定量实时聚合酶链反应（qRT-PCR）检测临床 OA 组织中的 circRNA-MSR、miR-761 和 FBXO21 的表达。通过用 LPS 处理 C28/I2 细胞并转染 circRNA-MSR、miR-761 和 FBXO21 的过表达或敲低载体以及自噬抑制剂 3-MA 构建体外 OA 模型。荧光原位杂交（FISH）确定 circRNA-MSR 和 miR-761 的位置。双荧光素酶报告基因实验评估 circRNA-MSR 和 miR-761 以及 miR-761 和 FBXO21 之间的结合。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐（MTT）法检测细胞活力。通过 Western blot 检测 LC3 II/I、p62 和 beclin 1 的表达。OA 中 circRNA-MSR 和 FBXO21 水平升高，而 miR-761 水平受到抑制。抑制 circRNA-MSR 促进了 LPS 处理细胞的自噬。circRNA-MSR 可以与 miR-761 结合并抑制其表达。circRNA-MSR 敲低抑制 LPS 处理 C28/I2 细胞中引起的自噬的作用被 miR-761 抑制所逆转。此外，miR-761 可以靶向 FBXO21 并抑制其表达。miR-761 过表达逆转了 LPS 处理 C28/I2 细胞中 miR-761 过表达引起的自噬增加。circRNA-MSR 可以通过靶向 miR-761 影响 FBXO21 水平，从而抑制 OA 软骨细胞的自噬，为 OA 治疗提供了新的靶点和策略。
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