Circ_0134111 knockdown relieves IL-1β-induced apoptosis, inflammation and extracellular matrix degradation in human chondrocytes through the circ_0134111-miR-515-5p-SOCS1 network

Abstract

Background: Osteoarthritis (OA) is characterized by chondrocyte injury and dysfunction, such as excessive apoptosis, inflammatory response and extracellular matrix (ECM) degradation. Circular RNA (circRNA) deregulation is reported to be involved in OA. Our study aimed to explore the role of circ_0134111 in OA.

Methods: Human chondrocytes were treated with interleukin-1β (IL-1β) to mimic OA cell model. The expression of circ_0134111, miR-515-5p and suppressor of cytokine signaling 1 (SOCS1) mRNA was measured by real-time quantitative polymerase chain reaction (RT-qPCR), and the protein levels of SOCS1 and apoptosis-/inflammation-/ECM-related markers were determined by western blot. Cell proliferation and cell apoptosis were assessed using cell counting kit-8 (CCK-8) and flow cytometry assay, respectively. For mechanism analysis, the predicted interaction between miR-515-5p and circ_0134111 or SOCS1 was verified by dual-luciferase reporter assay, pull-down assay and RNA immunoprecipitation (RIP) assay. Rescue experiments were performed to explore the interplay between miR-515-5p and circ_0134111 or SOCS1.

Results: Circ_0134111 was overexpressed in OA cartilage tissues and IL-1β-induced chondrocytes. IL-1β-induced chondrocyte apoptosis, inflammatory responses and ECM degradation were alleviated by circ_0134111 knockdown or miR-515-5p restoration. Circ_0134111 acted as miR-515-5p sponge to regulate miR-515-5p expression, and miR-515-5p deficiency reversed the effects of circ_0134111 knockdown in IL-1β-induced chondrocytes. MiR-515-5p directly bound to SOCS1, and circ_0134111 decoyed miR-515-5p to increase SOCS1 level. MiR-515-5p restoration alleviated IL-1β-induced chondrocyte apoptosis, inflammatory responses and ECM degradation, While SOCS1 overexpression partly abolished these effects.

Conclusion: Circ_0134111 knockdown alleviated apoptosis, inflammatory responses and ECM degradation in OA cell model by mediating the miR-515-5p-SOCS1 network, hinting that circ_0134111 was involved in OA progression.

Keywords: Chondrocyte; Osteoarthritis; SOCS1; circ_0134111; miR-515-5p.