Exosome-mediated circ_0001846 participates in IL-1β-induced chondrocyte cell damage by miR-149-5p-dependent regulation of WNT5B

Abstract

Aims: Osteoarthritis (OA) is the leading cause of physical disability in middle-aged and elderly people globally. Previous studies have revealed that circular RNA (circRNA) is involved in the pathogenesis of OA. In this study, we studied the role of circ_0001846 in interleukin-1β (IL-1β)-induced OA progression.

Methods: Twenty-one patients with OA and 17 volunteers were recruited for the collection of articular cartilage tissues. The expression of circ_0001846, microRNA-149-5p (miR-149-5p) and Wingless-type MMTV integration site family, member 5B (WNT5B) was detected by quantitative real-time polymerase chain reaction. The protein expression was determined by western blot analysis. Cell viability, apoptosis, invasion and migration were demonstrated by cell counting kit-8, flow cytometry analysis, transwell invasion and wound-healing assays, respectively. The levels of IL-6 and tumor necrosis factor-α were detected by Enzyme-linked immunosorbent assay. The interaction between miR-149-5p and circ_0001846 or WNT5B was predicted by starbase online database, and proved by dual-luciferase reporter and RIP assays.

Results: Circ_0001846 and WNT5B expression were upregulated, while miR-149-5p expression was downregulated in articular cartilage tissues from patients with OA and IL-1β-treated CHON-001 cells compared with normal articular cartilage tissues or untreated CHON-001 cells. Circ_0001846 expression was increased in IL-1β-treated CHON-001 cell exosomes. Circ_0001846 knockdown reversed IL-1β-mediated cell proliferation, apoptosis, migration, invasion, inflammation and extracellular matrix (ECM) degradation in CHON-001 cells. Additionally, circ_0001846 participated in IL-1β-induced chondrocyte cell damage by sponging miR-149-5p. MiR-149-5p mediated IL-1β-induced chondrocyte cell dysfunction by targeting WNT5B. Furthermore, circ_0001846 secretion was mediated by exosomes in IL-1β-treated CHON-001 cells.

Conclusion: Exosome-mediated transfer of circ_0001846 modulated IL-1β-induced chondrocyte cell damage by miR-149-5p/WNT5B axis, providing a novel avenue for the therapy of OA.

Keywords: Exosomes; OA; WNT5B; circ_0001846; miR-149-5p.