Yao Teng, Yang Yute, Xie Ziang, Xu Yining, Huang Yizhen, Gao Jun, Shen Shuying, Ye Huali, Iranmanesh Yasaman, Fan Shunwu, Ma Jianjun
Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou, China.
Front Cell Dev Biol. 2021 Jan 15;8:579945. doi: 10.3389/fcell.2020.579945. eCollection 2020.
Osteoarthritis (OA) is a degenerative joint disease. Currently, apart from symptomatic treatment or joint replacement, no other effective treatments for OA exist. The mechanisms underlying OA remain elusive and require further research. Circular RNAs (circRNAs) are known to be involved in many diseases; however, their function in OA is not yet fully understood. Here, we identified a novel circRNA, Circ0083429. The role of Circ0083429 in OA was confirmed via western blot (WB), quantitative real-time PCR (qRT-PCR), and immunofluorescence (IF) through knockdown and overexpression experiments. The binding of Circ0083429 to downstream miR-346 and its target gene SMAD3 was predicted via bioinformatics analysis and verified using a luciferase reporter assay and RNA pulldown experiments. Finally, the function of Circ0083429 was evaluated in mouse OA models. In our study, we found that Circ0083429 regulates the homeostasis of the extracellular matrix (ECM) in human chondrocytes. Mechanistically, Circ0083429 affects OA by regulating the mRNA level of through the sponging of microRNA (miRNA)-346. Injecting adeno-associated virus Circ0083429 into the intra-junction of the mouse knee alleviated OA. In conclusion, Circ0083429 regulates the ECM via the regulation of the downstream miRNA-346/ in human chondrocytes, which provides a new therapeutic strategy for OA.
骨关节炎(OA)是一种退行性关节疾病。目前,除了对症治疗或关节置换外,尚无其他针对OA的有效治疗方法。OA的潜在机制仍不清楚,需要进一步研究。已知环状RNA(circRNA)参与多种疾病;然而,它们在OA中的功能尚未完全了解。在此,我们鉴定了一种新型circRNA,即Circ0083429。通过蛋白质免疫印迹法(WB)、定量实时聚合酶链反应(qRT-PCR)以及免疫荧光法(IF),经敲低和过表达实验证实了Circ0083429在OA中的作用。通过生物信息学分析预测了Circ0083429与下游miR-346及其靶基因SMAD3的结合,并使用荧光素酶报告基因检测和RNA下拉实验进行了验证。最后,在小鼠OA模型中评估了Circ0083429的功能。在我们的研究中,我们发现Circ0083429调节人软骨细胞中细胞外基质(ECM)的稳态。机制上,Circ0083429通过海绵吸附微小RNA(miRNA)-346来影响OA,调节的mRNA水平。将腺相关病毒Circ0083429注射到小鼠膝关节内缓解了OA。总之,Circ0083429通过调节人软骨细胞中下游miRNA-346/来调节ECM,这为OA提供了一种新的治疗策略。