Zhao Yongzhao, Xiang Qian, Cheng Yunzhong, Lin Jialiang, Jiang Shuai, Li Weishi
Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
Beijing Key Laboratory of Spinal Disease Research, Beijing, China.
Stem Cells Int. 2022 Oct 3;2022:6082377. doi: 10.1155/2022/6082377. eCollection 2022.
Stem cell therapy is a promising therapeutic modality for intervertebral disc degeneration (IDD). Oxidative stress is a vital contributor to the IDD; however, the definite role of oxidative stress in stem cell therapy for IDD remains obscure. The aim of this study was to determine the vital role of oxidative stress-related differentially expressed genes (OSRDEGs) in degenerative NPCs cocultured with mesenchymal stem cells (MSCs).
A series of bioinformatic methods were used to calculate the oxidative stress score and autophagy score, identify the OSRDEGs, conduct the function enrichment analysis and protein-protein interaction (PPI) analysis, build the relevant competing endogenous RNA (ceRNA) regulatory networks, and explore the potential association between oxidative stress and autophagy in degenerative NPCs cocultured with MSCs.
There was a significantly different oxidative stress score between NPC/MSC samples and NPC samples ( < 0.05). Forty-one OSRDEGs were selected for the function enrichment and PPI analyses. Ten hub OSRDEGs were obtained according to the PPI score, including JUN, CAT, PTGS2, TLR4, FOS, APOE, EDN1, TXNRD1, LRRK2, and KLF2. The ceRNA regulatory network, which contained 17 DElncRNAs, 240 miRNAs, and 10 hub OSRDEGs, was constructed. Moreover, a significant relationship between the oxidative stress score and autophagy score was observed ( < 0.05), and 125 significantly related gene pairs were obtained (|| > 0.90, < 0.05).
Stem cell therapy might repair the degenerative IVD via reducing the oxidative stress through the ceRNA regulatory work and restoration of autophagy in degenerative NPCs. This research could provide new insights into the mechanism research of stem cell therapy for IDD and potential therapeutic targets in the IDD treatment.
干细胞疗法是一种治疗椎间盘退变(IDD)的有前景的治疗方式。氧化应激是IDD的一个重要促成因素;然而,氧化应激在干细胞治疗IDD中的明确作用仍不清楚。本研究的目的是确定氧化应激相关差异表达基因(OSRDEGs)在与间充质干细胞(MSCs)共培养的退变髓核细胞(NPCs)中的重要作用。
采用一系列生物信息学方法计算氧化应激评分和自噬评分,鉴定OSRDEGs,进行功能富集分析和蛋白质-蛋白质相互作用(PPI)分析,构建相关的竞争性内源RNA(ceRNA)调控网络,并探讨在与MSCs共培养的退变NPCs中氧化应激与自噬之间的潜在关联。
NPC/MSC样本与NPC样本之间的氧化应激评分存在显著差异(<0.05)。选择41个OSRDEGs进行功能富集和PPI分析。根据PPI评分获得10个核心OSRDEGs,包括JUN、CAT、PTGS2、TLR4、FOS、APOE、EDN1、TXNRD1、LRRK2和KLF2。构建了包含17个差异表达长链非编码RNA(DElncRNAs)、240个微小RNA(miRNAs)和10个核心OSRDEGs的ceRNA调控网络。此外,观察到氧化应激评分与自噬评分之间存在显著关系(<0.05),并获得125对显著相关的基因对(||>0.90,<0.05)。
干细胞疗法可能通过ceRNA调控作用降低氧化应激并恢复退变NPCs中的自噬,从而修复退变的椎间盘。本研究可为IDD的干细胞治疗机制研究及IDD治疗中的潜在治疗靶点提供新的见解。