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

Abstract

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.

Research progress and hotspots on macrophages in osteoarthritis: A bibliometric analysis from 2009 to 2022

“…[ 28 ] Therefore, reducing synovitis may be an effective way to delay cartilage degeneration, and macrophages are the best diagnostic markers for immune infiltration of bone and joint synovitis. [ 29 ] To quickly and accurately understand the current research situation and future trends, we use bibliometrics to analyze the papers from 2009 to 2022, providing reference data for researchers.…”

“…[37] It has been reported that both immune system processes and inflammation play roles in the progression of OA. Through KEGG analysis, Liao et al [29] learned that differentially expressed genes in OA synovium are mainly involved in immune-related pathways such as the TNF signaling pathway, NF-KB signaling pathway, MAPK signaling pathway, and T-cell receptor signaling pathway. As indicative of the current research situation, our screening results also found that the "T cells" in Cluster 2 are one of the most frequently used keywords.…”

Natural anti‐inflammatory products for osteoarthritis: From molecular mechanism to drug delivery systems and clinical trials

“…), scientists reported the M1 macrophages increasing in synovium and synovia even before the cartilage degradation (Sun, Panchal, et al, 2017). Another differentially expressed and gene screening study reports that cells including M2 macrophage and memory B cell, as well as CCL signaling pathways (which have the greatest communication between macrophage and T cells), are significantly associated with OA (Liao et al, 2022). However, it is worth knowing that the expression of CD40 has been demonstrated not highly correlated with OA but with RA in an early study (Gotoh et al, 2004).…”

The novel angiogenesis regulator circFAM169A promotes the metastasis of colorectal cancer through the angiopoietin-2 signaling axis

“…Gene set variation analysis (GSVA) were used to estimate the relative enrichment of a gene set of interest over a sample population, which is used to observe the variation in the activity of a set of genes corresponding to a particular biological process [ 15 ]. Followed by previous study [ 16 ], the GSVA R package [ 17 ] was used to analyze the pathway between two different groups of samples, and the defined gene set: HALLMARKS was downloaded from the Molecular Signature Database. “zscore” algorithm was used to give score to each sample and used this enrichment score to represent the degree of absolute enrichment of a gene set hallmark, while different scores also represent the activity degree of the hallmarks in the sample.…”