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

Aging (Albany NY). 2021 Aug 19;13(16):20383-20394. doi: 10.18632/aging.203420. Epub 2021 Aug 19.

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.

Keywords: chondrocytes; hsa_circ_0134111; miR-224-5p; osteoarthritis; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Chemokine CCL1 / genetics*
  • Chemokine CCL1 / metabolism
  • Chondrocytes / metabolism
  • Disease Progression
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Osteoarthritis / genetics*
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Osteoarthritis / physiopathology
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • Rats
  • Rats, Wistar

Substances

  • Chemokine CCL1
  • IL1B protein, human
  • Interleukin-1beta
  • MIRN224 microRNA, human
  • MicroRNAs
  • RNA, Circular