Circ_0020014 mediates CTSB expression and participates in IL-1β-prompted chondrocyte injury via interacting with miR-24-3p

by Selleckchem | Dec 26 2023

Background: Recent studies have shown that circRNAs are involved in the pathogenesis of osteoarthritis (OA) by affecting various fundamental cellular characteristics of chondrocytes. The purpose of this paper is to investigate the role and regulatory mechanism of hsa_circ_0020014 (circ_0020014) in chondrocytes of OA.

Methods: The inflammatory cytokine interleukin 1 beta (IL-1β) was used to stimulate human chondrocytes. Cell viability, proliferation, and apoptosis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), 5-Ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays. Several protein levels were determined by western blotting (WB). Levels of inflammatory cytokines and malondialdehyde (MDA) were determined by enzyme-linked immunosorbent assay (ELISA). Relative expression of circ_0020014 was estimated by real-time polymerase quantitative chain reaction (RT-qPCR). Bioinformatics prediction combined with dual-luciferase reporter, RIP and RNA pull-down assays were done to probe into the regulatory mechanism of circ_0020014.

Results: Circ_0020014 was overexpressed in OA patient-derived articular cartilages and IL-1β-stimulated chondrocytes. Silencing of circ_0020014 lighted IL-1β-prompted chondrocyte proliferation repression, apoptosis, inflammation, and oxidative stress. Mechanically, circ_0020014 functioned as a miR-24-3p molecular sponge to regulate cathepsin B (CTSB) expression. Furthermore, miR-24-3p inhibition alleviated circ_0020014 knockdown-mediation repression of IL-1β-urged chondrocyte injury. In addition, CTSB overexpression whittled miR-24-3p upregulation-mediated suppression of IL-1β-urged chondrocyte injury.

Conclusion: Our findings demonstrated that the circ_0020014/miR-24-3p/CTSB axis was associated with IL-1β-prompted chondrocyte injury, supporting the involvement of circ_0020014 in the OA pathogenesis.

Comments:

This research seems to focus on understanding the role of a specific circular RNA, circ_0020014, in osteoarthritis (OA). It delves into how this circRNA impacts fundamental cellular characteristics of chondrocytes, the cartilage cells affected in OA.

From what I gather, the study used interleukin 1 beta (IL-1β) to induce an inflammatory response in human chondrocytes. The results highlighted that circ_0020014 is overexpressed in OA-affected cartilages and in IL-1β-stimulated chondrocytes. When circ_0020014 was silenced, it seemed to alleviate various detrimental effects triggered by IL-1β, such as decreased chondrocyte proliferation, increased apoptosis, inflammation, and oxidative stress.

The study suggests that circ_0020014 acts as a sponge for miR-24-3p, a microRNA, thereby regulating the expression of cathepsin B (CTSB). This regulation seems to impact the injury caused to chondrocytes by IL-1β. When miR-24-3p was inhibited, the negative effects of circ_0020014 knockdown were reduced. Conversely, increasing CTSB levels seemed to diminish the suppression caused by miR-24-3p upregulation.

Overall, this research implies that the circ_0020014/miR-24-3p/CTSB axis plays a role in the injury chondrocytes experience due to IL-1β, potentially contributing to the development or progression of OA.