Zhang Jiaming, Hao Xiaoxia, Chi Ruimin, Liu Jiawei, Shang Xingru, Deng Xiaofeng, Qi Jun, Xu Tao
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Genet. 2022 Mar 3;13:821508. doi: 10.3389/fgene.2022.821508. eCollection 2022.
Osteoarthritis (OA) is a common degenerative joint disease. The aims of this study are to explore the effects of mechanical stress on whole transcriptome landscape and to identify a non-coding transcriptome signature of mechanical stress. Next-generation RNA sequencing (RNA-seq) was performed on IL-1β-induced OA-like chondrocytes stimulated by mechanical stress. Integrated bioinformatics analysis was performed and further verified by experimental validations. A total of 5,022 differentially expressed mRNAs (DEMs), 88 differentially expressed miRNAs (DEMIs), 1,259 differentially expressed lncRNAs (DELs), and 393 differentially expressed circRNAs (DECs) were identified as the transcriptome response to mechanical stress. The functional annotation of the DEMs revealed the effects of mechanical stress on chondrocyte biology, ranging from cell fate, metabolism, and motility to endocrine, immune response, and signaling transduction. Among the DELs, ∼92.6% were identified as the novel lncRNAs. According to the co-expressing DEMs potentially regulated by the responsive DELs, we found that these DELs were involved in the modification of immune and metabolism. Moreover, immune- and metabolism-relevant DELs exhibited a notable involvement in the competing endogenous RNA (ceRNA) regulation networks. Silencing lncRNA attenuated cellular senescence induced by mechanical stress. Moreover, the expression of was elevated by mechanical stress, which was rescued by silencing . The transcriptome landscape of IL-1β-induced OA-like chondrocytes was remarkably remodeled by mechanical stress. This study identified an immune- and metabolism-related ncRNA transcriptome signature responsive to mechanical stress and provides an insight of ncRNAs into chondrocyte biology and OA.
骨关节炎（OA）是一种常见的退行性关节疾病。本研究的目的是探讨机械应力对全转录组图谱的影响，并确定机械应力的非编码转录组特征。对经机械应力刺激的白细胞介素-1β诱导的骨关节炎样软骨细胞进行了下一代RNA测序（RNA-seq）。进行了综合生物信息学分析，并通过实验验证进一步证实。共鉴定出5022个差异表达的mRNA（DEM）、88个差异表达的miRNA（DEMI）、1259个差异表达的lncRNA（DEL）和393个差异表达的circRNA（DEC）作为对机械应力的转录组反应。对DEM的功能注释揭示了机械应力对软骨细胞生物学的影响，范围从细胞命运、代谢和运动到内分泌、免疫反应和信号转导。在DEL中，约92.6%被鉴定为新型lncRNA。根据可能受反应性DEL调控的共表达DEM，我们发现这些DEL参与了免疫和代谢的调节。此外，与免疫和代谢相关的DEL在竞争性内源RNA（ceRNA）调控网络中表现出显著的参与。沉默lncRNA可减轻机械应力诱导的细胞衰老。此外，机械应力使 的表达升高，而沉默 可使其恢复。机械应力显著重塑了白细胞介素-1β诱导的骨关节炎样软骨细胞的转录组图谱。本研究确定了一种对机械应力有反应的免疫和代谢相关ncRNA转录组特征，并为ncRNA在软骨细胞生物学和骨关节炎中的作用提供了见解。
