Hsa_circ_0007292 promotes chondrocyte injury in osteoarthritis via targeting the miR-1179/HMGB1 axis

Abstract

Abstract Background Circular RNAs (circRNAs) have been demonstrated to participate in the progression of osteoarthritis (OA). This study aimed to investigate the role and molecular mechanism of hsa_circ_0007292 in OA. Methods Hsa_circ_0007292 was identified by analyzing a circRNA microarray from the Gene Expression Omnibus (GEO) database, and its expression was detected by real-time PCR in OA cartilage tissues and interleukin (IL)-1β-induced two human chondrocytes (CHON-001 and C28/I2), the OA cell models. The effects of hsa_circ_0007292 knockdown and miR-1179 overexpression on IL-1β-induced chondrocyte injury were examined by CCK-8, BrdU, flow cytometry, ELISA, and western blot. RNA pull-down assay and dual-luciferase reporter gene assay were used to analyze the interaction between hsa_circ_0007292 and miR-1179. Rescue experiments were carried out to determine the correlations among hsa_circ_0007292, miR-1179 and high mobility group box-1 (HMGB1). Results Hsa_circ_0007292 expression was upregulated in OA tissues and IL-1β-induced chondrocytes. Both downregulation of hsa_circ_0007292 and miR-1179 overexpression increased the proliferation and Aggrecan expression, suppressed apoptosis, matrix catabolic enzyme MMP13 expression and inflammatory factor (TNF‐α, IL‐6, and IL‐8) levels. There was a negative correlation between hsa_circ_0007292 and miR-1179, and a positive correlation between hsa_circ_0007292 and HMGB1 in OA tissues. The mechanistic study showed that hsa_circ_0007292 prevented HMGB1 downregulation by sponging miR-1179. Upregulation of HMGB1 could reverse the influence of hsa_circ_0007292 downregulation on IL-1β-induced chondrocyte injury. Conclusions Downregulation of hsa_circ_0007292 relieved apoptosis, extracellular matrix degradation and inflammatory response in OA via the miR-1179/HMGB1 axis, suggesting that hsa_circ_0007292 might be a potential therapeutic target for OA treatment.