Orthopedic Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
Stem Cell Research and Cellular Therapy Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
J Orthop Surg Res. 2023 Jul 29;18(1):544. doi: 10.1186/s13018-023-04026-7.
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.
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).
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.
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.
环状 RNA（circRNAs）已被证明参与骨关节炎（OA）的进展。本研究旨在探讨 hsa_circ_0007292 在 OA 中的作用和分子机制。
通过分析基因表达综合数据库（GEO）中的 circRNA 微阵列鉴定 hsa_circ_0007292，并用实时 PCR 检测 OA 软骨组织和白细胞介素（IL）-1β诱导的两种人软骨细胞（CHON-001 和 C28/I2）中 hsa_circ_0007292 的表达，OA 细胞模型。通过 CCK-8、BrdU、流式细胞术、ELISA 和 Western blot 检测 hsa_circ_0007292 敲低和 miR-1179 过表达对 IL-1β诱导的软骨细胞损伤的影响。RNA 下拉实验和双荧光素酶报告基因实验用于分析 hsa_circ_0007292 与 miR-1179 之间的相互作用。进行挽救实验以确定 hsa_circ_0007292、miR-1179 和高迁移率族蛋白 B1（HMGB1）之间的相关性。
OA 组织和 IL-1β诱导的软骨细胞中 hsa_circ_0007292 表达上调。hsa_circ_0007292 下调和 miR-1179 过表达均增加了增殖和聚集蛋白聚糖表达，抑制了细胞凋亡、基质代谢酶 MMP13 表达和炎症因子（TNF-α、IL-6 和 IL-8）水平。OA 组织中 hsa_circ_0007292 与 miR-1179 呈负相关，hsa_circ_0007292 与 HMGB1 呈正相关。机制研究表明，hsa_circ_0007292 通过海绵吸附 miR-1179 防止 HMGB1 下调。HMGB1 的上调可逆转 hsa_circ_0007292 下调对 IL-1β诱导的软骨细胞损伤的影响。
hsa_circ_0007292 通过 miR-1179/HMGB1 轴缓解 OA 中的细胞凋亡、细胞外基质降解和炎症反应，提示 hsa_circ_0007292 可能是 OA 治疗的潜在治疗靶点。
