CRNDE alleviates IL-1β-induced chondrocyte damage by modulating miR-31/NF-κB pathway.

Abstract

Background: The long non-coding RNA CRNDE (CRNDE) has been identified as a lncRNA associated with osteoarthritis (OA), playing a role the age-related degeneration of articular cartilage. However, the precise mechanism by which CRNDE affects the physiological functions of OA chondrocytes remains unclear.

Methods: To simulate the inflammatory conditions observed in OA, interleukin (IL)-1β-stimulated chondrocyte C-28/I2 cells were utilized. The expression levels of CRNDE and miR-31 were assessed using reverse transcription-polymerase chain reaction (RT-PCR). Chondrocyte viability and apoptosis were evaluated through CCK-8 assay and flow cytometry, respectively. The levels of IL-6, IL-1β and Tumor necrosis factor (TNF-α) were determined using enzyme-linked immunosorbent assay (ELISA). mRNA expression levels of MMP-13, Aggrecan and COL2A1 were detected by quantitative RT-PCR. Western blot analysis was performed to evaluate the protein levels of factors related to cartilage matrix degradation, including p-p65, p65 and p-IκBα of the NF-κB pathway.

Results: CRNDE expression was downregulated in both OA cartilage tissues and IL-1β-stimulated chondrocytes. Overexpression of CRNDE mitigated IL-1β-stimulated chondrocytes apoptosis, inflammatory responses, and cartilage matrix degradation. Compared with healthy controls, OA tissues exhibited reduced expression of miR-31, which was negatively correlated with the expression of CRNDE. Additionally, overexpression of miR-31 partially reversed the inhibitory effects of CRNDE on apoptosis, inflammation, cartilage matrix degradation, and the inactivation of Nuclear factor (NF)-κB pathway induced by IL-1β stimulation. Moreover, silencing of CRNDE exacerbated IL-1β-induced chondrocytes damage, which was aliviated by the NF-κB pathway inhibitor, Bay 11-7082.

Conclusion: CRNDE alleviated IL-1β-induced injuries in OA chondrocytes by suppressing the miR-31-mediated NF-κB signaling pathway.