Li Bin, Ding Tao, Chen Haoyi, Li Changwei, Chen Bo, Xu Xing, Huang Ping, Hu Fangqiong, Guo Lei
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Bone Joint Res. 2023 Jan;12(1):33-45. doi: 10.1302/2046-3758.121.BJR-2022-0231.R1.
Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of in osteoarthritis.
Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression.
Tensile strain could decrease the expression of in chondrocytes. expression was significantly decreased in human and mouse OA cartilage tissues and chondrocytes. could inhibit matrix metabolism of chondrocytes through competitively 'sponging' miRNA-9-5p targeting Kruppel-like factor 5 (), indicating that the decrease in might be a protective factor in mechanical instability-induced OA. The tensile strain stimulated chondrocytes to secrete exosomal miR-9-5p. Exosomes with high expression from chondrocytes could inhibit osteoblast differentiation by targeting . Intra-articular injection of exosomal alleviated the progression of OA induced by destabilized medial meniscus surgery in mice.
Taken together, these results demonstrate that reduction of causes an increase in , which acts as a protective factor in mechanical instability-induced OA, and provides a novel mechanism of communication among joint components and a potential application for the treatment of OA.Cite this article: 2023;12(1):33-45.
环状RNA(circRNA)参与炎症因子或氧化应激诱导的关节软骨退变的调控。在先前的一项研究中,我们发现[此处原文缺失具体circRNA名称]在骨关节炎(OA)患者和OA小鼠的软骨细胞中表达显著降低。因此,本文旨在探讨[此处原文缺失具体circRNA名称]在骨关节炎中的作用及机制。
采用RNA测序、荧光原位杂交和定量实时聚合酶链反应(qRT-PCR)检测[此处原文缺失具体circRNA名称]在人和小鼠OA软骨组织及软骨细胞中的表达。然后通过周期性拉伸应变刺激软骨细胞分泌外泌体miR-9-5p。对不稳定内侧半月板(DMM)手术诱导的模型进行关节内注射外泌体miR-9-5p以减轻OA进展。
拉伸应变可降低软骨细胞中[此处原文缺失具体circRNA名称]的表达。在人和小鼠OA软骨组织及软骨细胞中,[此处原文缺失具体circRNA名称]表达显著降低。[此处原文缺失具体circRNA名称]可通过竞争性“吸附”靶向Kruppel样因子5([此处原文缺失具体基因名称])的miRNA-9-5p来抑制软骨细胞的基质代谢,表明[此处原文缺失具体circRNA名称]的降低可能是机械不稳定诱导OA中的一个保护因子。拉伸应变刺激软骨细胞分泌外泌体miR-9-5p。来自软骨细胞的高表达[此处原文缺失具体circRNA名称]的外泌体可通过靶向[此处原文缺失具体基因名称]抑制成骨细胞分化。关节内注射外泌体[此处原文缺失具体circRNA名称]可减轻小鼠不稳定内侧半月板手术诱导的OA进展。
综上所述,这些结果表明[此处原文缺失具体circRNA名称]的减少导致[此处原文缺失具体基因名称]增加,[此处原文缺失具体基因名称]在机械不稳定诱导的OA中起保护因子作用,并提供了关节组件间通讯的新机制及OA治疗的潜在应用。引用本文:2023;12(1):33 - 45。