Comprehensive bulk and single-cell transcriptome profiling give useful insights into the characteristics of osteoarthritis associated synovial macrophages

Frontiers in Immunology

Immunology

Ming Yang¹  Dandan Li²  Donge Tang²  Tingting Deng³  Shengyou Liao³  Yujie Wang³  Ye Wu⁴  Guohui Nie⁵  Xiaoqin Fan⁶  Ni Xie⁷  Xinying Liu⁷  Hong Sun⁷  Jingxiao Lu⁷ 

[1] Department of Otolaryngology, Shenzhen First People’s Hospital, The Affiliated Hospital of Jinan University, Shenzhen, Guangdong, China;Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, the Second Clinical Medical College of Jinan University, the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen People’s Hospital, Shenzhen, China;Shenzhen Key Laboratory of Nanozymes and Translational Cancer Research, Department of Otolaryngology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, China;Shenzhen Key Laboratory of Nanozymes and Translational Cancer Research, Department of Otolaryngology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, China;Department of Otolaryngology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China;Shenzhen Key Laboratory of Nanozymes and Translational Cancer Research, Department of Otolaryngology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, China;State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, China;Shenzhen Key Laboratory of Nanozymes and Translational Cancer Research, Department of Otolaryngology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, China;The Bio-bank of Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China;The Bio-bank of Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China;

关键词: osteoarthritis;    synovium;    immune infiltration;    macrophage;    Scissor analysis;   

DOI  :  10.3389/fimmu.2022.1078414

 received in 2022-11-02, accepted in 2022-12-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundOsteoarthritis (OA) is a common chronic joint disease, but the association between molecular and cellular events and the pathogenic process of OA remains unclear.ObjectiveThe study aimed to identify key molecular and cellular events in the processes of immune infiltration of the synovium in OA and to provide potential diagnostic and therapeutic targets.MethodsTo identify the common differential expression genes and function analysis in OA, we compared the expression between normal and OA samples and analyzed the protein–protein interaction (PPI). Additionally, immune infiltration analysis was used to explore the differences in common immune cell types, and Gene Set Variation Analysis (GSVA) analysis was applied to analyze the status of pathways between OA and normal groups. Furthermore, the optimal diagnostic biomarkers for OA were identified by least absolute shrinkage and selection operator (LASSO) models. Finally, the key role of biomarkers in OA synovitis microenvironment was discussed through single cell and Scissor analysis.ResultsA total of 172 DEGs (differentially expressed genes) associated with osteoarticular synovitis were identified, and these genes mainly enriched eight functional categories. In addition, immune infiltration analysis found that four immune cell types, including Macrophage, B cell memory, B cell, and Mast cell were significantly correlated with OA, and LASSO analysis showed that Macrophage were the best diagnostic biomarkers of immune infiltration in OA. Furthermore, using scRNA-seq dataset, we also analyzed the cell communication patterns of Macrophage in the OA synovial inflammatory microenvironment and found that CCL, MIF, and TNF signaling pathways were the mainly cellular communication pathways. Finally, Scissor analysis identified a population of M2-like Macrophages with high expression of CD163 and LYVE1, which has strong anti-inflammatory ability and showed that the TNF gene may play an important role in the synovial microenvironment of OA.ConclusionOverall, Macrophage is the best diagnostic marker of immune infiltration in osteoarticular synovitis, and it can communicate with other cells mainly through CCL, TNF, and MIF signaling pathways in microenvironment. In addition, TNF gene may play an important role in the development of synovitis.

【 授权许可】

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Copyright © 2023 Liao, Yang, Li, Wu, Sun, Lu, Liu, Deng, Wang, Xie, Tang, Nie and Fan