Hsa_circ_0007292 通过靶向 miR-1179/HMGB1 轴促进骨关节炎软骨细胞损伤。

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

机构信息

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.

出版信息

J Orthop Surg Res. 2023 Jul 29;18(1):544. doi: 10.1186/s13018-023-04026-7.

DOI:10.1186/s13018-023-04026-7

PMID:37516834

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10386318/

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.

摘要

背景

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。

方法

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。

结果

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。