Research Paper Volume 13, Issue 16 pp 20383—20394
Hsa_circ_0134111 promotes osteoarthritis progression by regulating miR-224-5p/CCL1 interaction
- 1 Department of Imaging, First People’s Hospital of Lianyungang City, Lianyungang 222000, Jiangsu Province, China
Received: March 27, 2021 Accepted: July 17, 2021 Published: August 19, 2021https://doi.org/10.18632/aging.203420
How to Cite
Copyright: © 2021 Liu and Zhang. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.