Hsa_circ_0134111 promotes osteoarthritis progression by regulating miR-224-5p/CCL1 interaction

Abstract

Mechanical, metabolic, inflammatory, and immune factors contribute to the development of osteoarthritis (OA), a joint disease characterized by cartilage destruction. The circular RNA (circRNA) hsa_circ_0134111 is upregulated in the cartilage of OA patients; however, its potential role in OA pathogenesis and progression remains unexplored. In this study, the effects of hsa_circ_0134111 knockdown were evaluated in primary human chondrocytes treated with IL-1β to simulate OA, as well as in a rat model of OA. Hsa_circ_0134111 expression was upregulated in IL-1β-stimulated chondrocytes. CCK-8 and flow cytometry assays showed that hsa_circ_0134111 knockdown reversed IL-1β-induced cell decline by inhibiting apoptosis. Following prediction analysis of circRNA and miRNA targets, dual-luciferase reporter and silencing/overexpression assays suggested that a regulatory network composed of hsa_circ_0134111, miR-224-5p, and CCL1 modulates IL-1β-mediated OA-like effects in chondrocytes. Accordingly, CCL1 overexpression abrogated the prosurvival effects of hsa_circ_0134111 knockdown in vitro . Moreover, hsa_circ_0134111 silencing in vivo alleviated cartilage destruction in an OA rat model, decreased IL-6 and TNF-α levels in synovial fluid, and downregulated CCL1 expression in the affected joints. These results suggest that hsa_circ_0134111 contributes to OA development by binding to miR-224-5p, thereby releasing the inhibition that miR-224-5p exerts over CCL1.

Circ_0005526 contributes to interleukin-1β-induced chondrocyte injury in osteoarthritis via upregulating transcription factor 4 by interacting with miR-142-5p

“…disclosed that circ_0088036 accelerated the progression of rheumatoid arthritis via miR-140-3p-related sirtuin-1 (SIRT1) upregulation [ 32 ]. Additionally, circ_0134111 promoted OA chondrocyte damage by inhibiting miR-224-5p to induce overexpression of CC motif ligand 1 (CCL1) [ 33 ]. Circ_0045714 increased phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) level to regulate IL-1β-stimulated chondrocyte injury via serving as a ceRNA of miR-331-3p [ 23 ].…”

Hsa_circ_0134111 promotes intervertebral disc degeneration via sponging miR-578

“…Zhang et al [ 42 ] showed that knockdown of circ_0134111 alleviated osteoarthritis symptoms through sponging miR-224-5p. Liu et al [ 34 ] also found that circ_0134111 induced osteoarthritis development through modulating the miR-224-5p/CCL1 axis. In our study, we found that the same circRNA was upregulated in IDD tissue and its overexpression promoted aberrant NP cell phenotypes, including proliferation, cytokine expression, and ECM degradation…”

“…Growing evidence suggested that circRNAs play critical roles in cell functions, such as apoptosis, growth, metabolism, and ECM synthesis [ 28 , 29 ] circRNAs have also been promulgated as therapeutic targets in different diseases including neurological dysfunction, metabolic diseases, cancers, and cardiovascular diseases [ 30 – 33 ]. For instance, a recent study showed that circ_0134111 could induce osteoarthritis development through regulating miR-224-5p/CCL1 and miR-515-5p-SOCS1 axes [ 34 ].…”

Circular RNA MELK Promotes Chondrocyte Apoptosis and Inhibits Autophagy in Osteoarthritis by Regulating MYD88/NF‐κB Signaling Axis through MicroRNA‐497‐5p

“…For apoptosis analysis, 10 μL of annexin V-fluorescein isothiocyanate and 5 μL of PI were added. A FACSCalibur flow cytometer was employed for detection (BD Biosciences) [19].…”