Wu Zhen, Shou Lu, Wang Jian, Xu Xinwei
Department of Orthopedics.
Department of Pneumology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
Medicine (Baltimore). 2020 Aug 14;99(33):e21707. doi: 10.1097/MD.0000000000021707.
Osteoarthritis (OA) is a chronic degenerative joint disease with its onset closely related to the growth of synovial fibroblasts (SFs), yet the genes involved in are few reported. In our study, we aimed to identify the OA-associated key gene and pathways via the single-cell RNA sequencing (scRNA-seq) analysis on SFs.scRNA-seq data of SFs from OA sufferers were accessed from GEO database, then the genes involved in were subjected to principal component analysis (PCA) and T-Stochastic Neighbor Embedding (TSNE) Analysis. GO and KEGG enrichment analyses were performed to find the most enriched functions and pathways associated with marker genes and a PPI network was constructed to identify the key gene associated with OA occurrence.Findings revealed that marker genes in three cell types identified by TSNE were mainly activated in pathways firmly related to fibroblasts growth, such as extracellular matrix, immune and cell adhesion molecule binding-associated functions and pathways. Moreover, fibronectin1 (FN1) was validated as the key gene that was tightly related to the growth of SFs, as well as had the potential to play a key role in OA occurrence.Our study explored the key gene and pathways associated with OA occurrence, which were of great value in further investigation of OA diagnosis as well as pathogenesis.
骨关节炎（OA）是一种慢性退行性关节疾病，其发病与滑膜成纤维细胞（SFs）的生长密切相关，但涉及的相关基因报道较少。在我们的研究中，我们旨在通过对SFs进行单细胞RNA测序（scRNA-seq）分析来鉴定与OA相关的关键基因和通路。从GEO数据库获取OA患者SFs的scRNA-seq数据，然后对其中涉及的基因进行主成分分析（PCA）和T-随机邻域嵌入（TSNE）分析。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析以找到与标记基因相关的最富集功能和通路，并构建蛋白质-蛋白质相互作用（PPI）网络以鉴定与OA发生相关的关键基因。研究结果表明，TSNE鉴定出的三种细胞类型中的标记基因主要在与成纤维细胞生长密切相关的通路中被激活，如细胞外基质、免疫和细胞粘附分子结合相关的功能和通路。此外，纤连蛋白1（FN1）被验证为与SFs生长密切相关且在OA发生中可能起关键作用的关键基因。我们的研究探索了与OA发生相关的关键基因和通路，这对进一步研究OA的诊断和发病机制具有重要价值。
