Gao Lixia, He Tao, Hu Qingkui, Ma Yan
Department of Rehabilitation Medicine, Wuhan No.1 Hospital, 215 Zhongshan Avenue, Qiaokou District, Wuhan, Hubei, 430022, China.
College of Sports Medicine, Wuhan Sports University, Wuhan, Hubei, 430079, China.
Adv Rheumatol. 2024 Dec 30;64(1):92. doi: 10.1186/s42358-024-00429-0.
Osteoarthritis (OA) is a common degenerative joint disease. Circular RNA Phosphodiesterase 1 C (circ-PDE1C, hsa_circ_0134111) has participated in the IL-1β-induced chondrocyte damages. The objective of our study was to explore the molecular mechanism of circ-PDE1C.
Circ-PDE1C, microRNA-766-3p (miR-766-3p) or Small Glutamine Rich Tetratricopeptide Repeat Co-Chaperone Beta (SGTB) expression was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell counting kit-8 (CCK-8) assay and flow cytometry were used to analyze proliferation and apoptosis, respectively. Western blotting assay was performed for protein detection. The inflammatory cytokines were measured by Enzyme-linked immunosorbent assay (ELISA). Oxidative stress was assessed by commercial kits. Target analysis was conducted by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.
Circ-PDE1C was abnormally overexpressed in OA tissues and IL-1β-exposed chondrocytes. Downregulation of circ-PDE1C alleviated the IL-1β-induced cell apoptosis, inflammation, extracellular matrix degradation and oxidative stress. Circ-PDE1C could interact with miR-766-3p to serve as miRNA sponge. The function of si-circ-PDE1C was attributed to the inhibition of miR-766-3p. Additionally, miR-766-3p directly targeted the 3'UTR of SGTB. The miR-766-3p upregulation impeded the IL-1β-triggered cell damages through reducing the level of SGTB. Moreover, SGTB expression was regulated by circ-PDE1C via binding to miR-766-3p in IL-1β-induced chondrocytes.
Altogether, circ-PDE1C enhanced the IL-1β-induced dysfunction in chondrocytes via upregulating SGTB by targeting miR-766-3p.
骨关节炎（OA）是一种常见的退行性关节疾病。环状RNA磷酸二酯酶1C（circ-PDE1C，hsa_circ_0134111）参与了白细胞介素-1β（IL-1β）诱导的软骨细胞损伤。我们研究的目的是探讨circ-PDE1C的分子机制。
采用逆转录定量聚合酶链反应（RT-qPCR）检测circ-PDE1C、微小RNA-766-3p（miR-766-3p）或富含小谷氨酰胺的四肽重复共伴侣β（SGTB）的表达。分别使用细胞计数试剂盒-8（CCK-8）检测和流式细胞术分析细胞增殖和凋亡。采用蛋白质免疫印迹法进行蛋白质检测。通过酶联免疫吸附测定（ELISA）检测炎性细胞因子。使用商业试剂盒评估氧化应激。通过双荧光素酶报告基因检测和RNA免疫沉淀（RIP）检测进行靶点分析。
circ-PDE1C在OA组织和IL-1β刺激的软骨细胞中异常高表达。下调circ-PDE1C可减轻IL-1β诱导的细胞凋亡、炎症、细胞外基质降解和氧化应激。circ-PDE1C可与miR-766-3p相互作用，充当微小RNA海绵。si-circ-PDE1C的作用归因于对miR-766-3p的抑制。此外，miR-766-3p直接靶向SGTB的3'非翻译区（3'UTR）。miR-766-3p的上调通过降低SGTB水平来减轻IL-1β触发的细胞损伤。此外，在IL-1β诱导的软骨细胞中，circ-PDE1C通过与miR-766-3p结合来调节SGTB的表达。
总之，circ-PDE1C通过靶向miR-766-3p上调SGTB，增强了IL-1β诱导的软骨细胞功能障碍。
