Bioinformatics analysis to identify key genes and pathways influencing synovial inflammation in osteoarthritis

Abstract

Osteoarthritis (OA) is a chronic arthropathy that occurs in the middle-aged and elderly population. The present study aimed to identify gene signature differences between synovial cells from OA synovial membrane with and without inflammation, and to explain the potential mechanisms involved. The differentially expressed genes (DEGs) between 12 synovial membrane with inflammation and 12 synovial membrane without inflammation from the dataset GSE46750 were identified using the Gene Expression Omnibus 2R. The DEGs were subjected to enrichment analysis, protein-protein interaction (PPI) analysis and module analysis. The analysis results were compared with text-mining results. A total of 174 DEGs were identified. Gene Ontology enrichment results demonstrated that functional molecules encoded by the DEGs primarily had extracellular location, molecular functions predominantly involving ‘chemokine activity’ and ‘cytokine activity’, and were associated with biological processes, including ‘inflammatory response’ and ‘immune response’. The Kyoto Encyclopedia of Genes and Genomes results demonstrated that DEGS may function through pathways associated with ‘rheumatoid arthritis’, ‘chemokine signaling pathway’, ‘complement and coagulation cascades’, ‘TNF signaling pathway’, ‘intestinal immune networks for IgA production’, ‘cytokine-cytokine receptor interaction’, ‘allograft rejection’, ‘Toll-like receptor signaling pathway’ and ‘antigen processing and presentation’. The top 10 hub genes [interleukin (IL)6, IL8, matrix metallopeptidase (MMP)9, colony stimulating factor 1 receptor, FOS proto-oncogene, AP1 transcription factor subunit, insulin-like growth factor 1, TYRO protein tyrosine kinase binding protein, MMP3, cluster of differentiation (CD)14 and CD163] and four gene modules were identified from the PPI network using Cytoscape. In addition, text-mining was used to identify the commonly used drugs and their targets for the treatment of OA. It was initially verified whether the results of the present study were useful for the study of OA treatment targets and pathways. The present study provided insight for the molecular mechanisms of OA synovitis. The hub genes and associated pathways derived from analysis may be targets for OA treatment. IL8 and MMP9, which were validated by text-mining, may be used as molecular targets for the OA treatment, while other hub genes require further validation.

The relationship between synovial inflammation, structural pathology, and pain in post-traumatic osteoarthritis: differential effect of stem cell and hyaluronan treatment

“…There was evidence that Hymovis but not MSCs ameliorated later-stage OA-associated synovial Mmp9 upregulation. MMP9 is one of the key synovitis hub genes recently identified in human OA [50] and known to play a role in nociceptor sensitization [51]. In contrast, MSCs particularly when injected twice slowed the natural post-injury resolution of another of the key OA synovitis hub genes, Il6, which may in part explain their reduced effect on allodynia.…”

Identification of the Key Role of NF-κB Signaling Pathway in the Treatment of Osteoarthritis With Bushen Zhuangjin Decoction, a Verification Based on Network Pharmacology Approach

“…Predicting the Molecular Targets for OA Differentially expressed genes identified for OA patients were obtained from the Gene Expression Omnibus database (GEO, https://www.ncbi.nlm.nih.Gov/geo/) (Clough and Barrett, 2016). The series GSE46750 (https://www.ncbi.nlm.nih.gov/geo/query/ acc.cgi?acc GSE46750) (Lin et al, 2018) was selected to compare the gene expression profiles of inflammatory I and normal/ reactive (N/R) synoviocytes from the synovium of the same OA patient. Differential expression patterns were identified in two regions of the synovium in 12 patients undergoing total knee arthroplasty.…”

Recent Advances in Pharmacological Intervention of Osteoarthritis: A Biological Aspect

“…Third, several genes such as BMP3 ( He et al, 2018 ), rs1799750 ( Geng et al, 2018 ), and CHI3L1 ( Song et al, 2021 ) show an inhibitory effect on cartilage repair. Fourth, the genes that regulate the expression of inflammatory cytokines in chondrocytes mainly include renin ( Wu et al, 2019a ), ACE ( Wu et al, 2019a ), Ang II ( Wu et al, 2019a ), AT1R ( Wu et al, 2019a ), AT2R ( Wu et al, 2019a ), ATF3 ( Iezaki et al, 2016 ), PTGS2 ( Lin et al, 2018 ; Wang et al, 2020a ), CCL20 ( Lin et al, 2018 ), CHI3L1 ( Lin et al, 2018 ), LIF ( Lin et al, 2018 ), CXCL8 ( Lin et al, 2018 ), and CXCL12 ( Lin et al, 2018 ). Last but not least, COL6A3/ACTG1 ( Li et al, 2020a ) and fibronectin1 (FN1) ( Wu et al, 2020a ) were found involved in fibroblast transformation.…”