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

Abstract

BackgroundCircular 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.MethodsHsa_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).ResultsHsa_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.ConclusionsDownregulation 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.