Rheumatology Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, China.
Gene. 2020 Oct 5;757:144939. doi: 10.1016/j.gene.2020.144939. Epub 2020 Jul 5.
Osteoarthritis (OA) is a chronic degenerative change with high incidence and leads to a lower quality of life and a larger socioeconomic burden. This study aimed to explore potential crucial genes and pathways associated with OA that can be used as potential biomarkers forearly treatment. Single-cell gene expression profile of 1464 chondrocytes and 192 fibroblasts in OA were downloaded from the public database (GSE104782 and GSE109449) for subsequent analysis. A total of eight clusters in chondrocytes and three clusters in fibroblasts of OA were identified using the Seurat pipeline and the "SingleR" package for cell-type annotation. Moreover, 44 common marker-genes between fibroblastic-like chondrocytes and fibroblasts were identified and the focal adhesions pathway was further identified as a significant potential mechanism of OA via functional enrichment analysis. Further, the reverse transcription quantitative real-time PCR (RT-qPCR) experiments at tissue's and cellular level confirmed that two key marker-genes (COL6A3 and ACTG1) might participate in the progression of OA. Summarily, we inferred that chondrocytes in OA might up-regulate the expression of COL6A3 and ACTG1 to complete fibroblasts transformation through the focal adhesion pathway. These findings are expected to gain a further insight into the development of OA fibrosis process and provide a promising target for treatment for early OA.
骨关节炎(OA)是一种具有高发病率的慢性退行性病变,导致生活质量下降和更大的社会经济负担。本研究旨在探索与 OA 相关的潜在关键基因和途径,可作为早期治疗的潜在生物标志物。从公共数据库(GSE104782 和 GSE109449)下载了 1464 个软骨细胞和 192 个成纤维细胞的单细胞基因表达谱,用于后续分析。使用 Seurat 管道和“SingleR”包对软骨细胞中的 8 个簇和成纤维细胞中的 3 个簇进行细胞类型注释。此外,还鉴定了成纤维细胞样软骨细胞和成纤维细胞之间的 44 个共同标记基因,并通过功能富集分析进一步确定了粘着斑途径是 OA 的一个重要潜在机制。此外,在组织和细胞水平的逆转录定量实时 PCR(RT-qPCR)实验证实,两个关键标记基因(COL6A3 和 ACTG1)可能参与 OA 的进展。总之,我们推断 OA 中的软骨细胞可能通过粘着斑途径上调 COL6A3 和 ACTG1 的表达,从而完成成纤维细胞的转化。这些发现有望深入了解 OA 纤维化过程的发展,并为早期 OA 的治疗提供有前途的靶点。