Dadihanc Tuerxunjiang, Zhang Yong, Li Guo-Qing, Zhou Hai-Kang, Huang Jingyong, Zhang Xue, Li Zhi-Qiang, Ma Hai-Rong
State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Province, PR China.
Department of Orthopaedic Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Province, PR China.
Regen Ther. 2024 May 24;26:60-70. doi: 10.1016/j.reth.2024.04.011. eCollection 2024 Jun.
Osteoarthritis (OA) is the most frequently diagnosed chronic joint disease. CircSEC24A is significantly elevated in OA chondrocytes upon IL-1β stimulation. However, its biological function in OA is still not fully understood.
The circRNAs-miRNA-mRNA network was predicted by bioinformatics analysis. An OA chondrocytes model was established by IL-1β stimulation. The expression of circSEC24A, miR-107-5p, CASP3, apoptosis-related molecules and extracellular matrix (ECM) components were detected by Western blot and qRT-PCR. MTT assay and Annexin V/PI staining were employed to monitor cell viability and apoptosis, respectively. The interaction between circSEC24A and miR-107-5p, as well as the binding between miR-107-5p and CASP3 3' UTR were detected by luciferase reporter and RIP assays. Cytokine secretion was monitored by ELISA assay. The role of circSEC24A was also explored in anterior cruciate ligament transection (ACLT) rat models.
CircSEC24A and CASP3 were increased, but miR-107-5p was decreased in rat OA cartilage tissues and OA chondrocytes. CircSEC24A acted as a sponge of miR-107-5p. Knockdown of circSEC24A promoted chondrocyte proliferation, but suppressed chondrocyte apoptosis, ECM degradation and inflammation via sponging miR-107-5p. CASP3 was identified as a miR-107-5p target gene. MiR-107-5p mimics protected against OA progression via targeting CASP3. Silencing of circSEC24A alleviated OA progression in ACLT model.
CircSEC24A promotes OA progression through miR-107-5p/CASP3 axis.
骨关节炎（OA）是最常被诊断出的慢性关节疾病。在白细胞介素-1β刺激下，环状RNA SEC24A（circSEC24A）在OA软骨细胞中显著升高。然而，其在OA中的生物学功能仍未完全明确。
通过生物信息学分析预测环状RNA-微小RNA-信使RNA网络。用白细胞介素-1β刺激建立OA软骨细胞模型。通过蛋白质免疫印迹法和定量逆转录聚合酶链反应检测circSEC24A、微小RNA-107-5p（miR-107-5p）、半胱天冬酶3（CASP3）、凋亡相关分子和细胞外基质（ECM）成分的表达。分别采用MTT法和膜联蛋白V/碘化丙啶染色监测细胞活力和凋亡。通过荧光素酶报告基因和RNA免疫沉淀实验检测circSEC24A与miR-107-5p之间的相互作用，以及miR-107-5p与CASP3 3'非翻译区之间的结合。通过酶联免疫吸附测定监测细胞因子分泌。还在前交叉韧带横断（ACLT）大鼠模型中探究了circSEC24A的作用。
在大鼠OA软骨组织和OA软骨细胞中，circSEC24A和CASP3升高，但miR-107-5p降低。CircSEC24A作为miR-107-5p的海绵。敲低circSEC24A可促进软骨细胞增殖，但通过结合miR-107-5p抑制软骨细胞凋亡、ECM降解和炎症。CASP3被鉴定为miR-107-5p的靶基因。MiR-107-5p模拟物通过靶向CASP3预防OA进展。沉默circSEC24A可减轻ACLT模型中的OA进展。
CircSEC24A通过miR-107-5p/CASP3轴促进OA进展。
