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Single cell sequencing revealed the underlying pathogenesis of the development of osteoarthritis.

Gene. 2020 Oct 05;757:144939. Epub 2020 Jul 05
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摘要


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.

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