Abstract
BackgroundOsteoarthritis (OA) is one of the most common age-related degenerative diseases. In recent years, some studies have shown that pathological changes in the synovial membrane occur earlier than those in the cartilage in OA. However, the molecular mechanism of synovitis in the pathological process of OA has not been elucidated. This study aimed to identify novel biomarkers associated with OA and to emphasize the role of immune cells in the pathogenesis of OA.MethodsMicroarray datasets were obtained from the Gene Expression Omnibus (GEO) and ArrayExpress databases and were then analyzed using R software. To determine differential immune cell subtype infiltration, the CIBERSORT deconvolution algorithm was used. Quantitative reverse transcription PCR (qRT-PCR) was used to determine the relative expressions of selected genes. Besides, Western blotting was used to assess the protein expression levels in osteoarthritic chondrocytes.ResultsAfter analyzing the database profiles, two potential biomarkers, collagen type 3 alpha 1 chain (COL3A1), and matrix metalloproteinase 9 (MMP9), associated with OA were discovered, which were confirmed by qRT-PCR and Western blotting. Specifically, the results revealed that, as the concentration of IL-1β increased, so did the gene and protein expression levels of COL3A1 and MMP9.ConclusionThe findings provide valuable information and direction for future research into novel targets for OA immunotherapy and diagnosis and aids in the discovery of the underlying biological mechanisms of OA pathogenesis.
Highlights
Osteoarthritis (OA), one of the most common age-related degenerative diseases, is characterized by osteophyte formation, cartilage degeneration, and synovial inflammation (Luo et al, 2018; Wang et al, 2018), which eventually lead to loss of joint function due to the limited repair capacity of the cartilage (Kim et al, 2018)
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment revealed that synovial membrane DEGs were mainly enriched in cytokine–cytokine receptor interaction, mitogen-activated protein kinase (MAPK) pathway, and tumor necrosis factor (TNF) pathway (Figure 2A), while DEGs from cartilage samples were enriched in the PI3K/AKT pathway, cytokine–cytokine receptor interaction, FIGURE 3 | Screening of hub genes and functional analysis. (A) Twenty-one differentially expressed genes (DEGs) intersected between the cartilage samples and the synovial membrane samples. (B) Protein–protein interaction (PPI) network of the 21 DEGs and two hub genes screened by the degree method using cytoHubba
Gene Ontology (GO) functional enrichment analysis revealed that synovial membrane DEGs were mainly involved in leukocyte migration, regulation of inflammatory response, and collagen-containing extracellular matrix (Figure 2B), while cartilage DEGs were mainly involved in the collagen-containing extracellular matrix, neutrophil degranulation, and neutrophil activation involved in immune response (Figure 2D)
Summary
Osteoarthritis (OA), one of the most common age-related degenerative diseases, is characterized by osteophyte formation, cartilage degeneration, and synovial inflammation (Luo et al, 2018; Wang et al, 2018), which eventually lead to loss of joint function due to the limited repair capacity of the cartilage (Kim et al, 2018). The degenerative changes in the synovial membrane in OA occur earlier than those in the cartilage (Sakurai et al, 2019). OA synovitis is most likely caused by an innate immune response and is mediated by the expression of matrix-degrading enzymes, inflammatory cytokines, and chemokines (Gómez et al, 2015; Qadri et al, 2020). Some studies have shown that pathological changes in the synovial membrane occur earlier than those in the cartilage in OA.
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