Mechanism of immune infiltration in synovial tissue of osteoarthritis: a gene expression-based study.

BACKGROUND: Osteoarthritis is a chronic degenerative joint disease, and increasing evidences suggest that the pathogenic mechanism involves immune system and inflammation. AIMS: The aim of current study was to uncover hub genes linked to immune infiltration in osteoarthritis synovial tissue using comprehensive bioinformatics analysis and experimental confirmation. METHODS: Multiple microarray datasets (GSE55457, GSE55235, GSE12021 and GSE1919) for osteoarthritis in Gene Expression Omnibus database were downloaded for analysis. Differentially expressed genes (DEGs) were identified using Limma package in R software, and immune infiltration was evaluated by CIBERSORT algorithm. Then weighted gene co-expression network analysis (WGCNA) was performed to uncover immune infiltration-associated gene modules. Protein-protein interaction (PPI) network was constructed to select the hub genes, and the tissue distribution of these genes was analyzed using BioGPS database. Finally, the expression pattern of these genes was confirmed by RT-qPCR using clinical samples. RESULTS: Totally 181 DEGs between osteoarthritis and normal control were screened. Macrophages, mast cells, memory CD4 T cells and B cells accounted for the majority of immune cell composition in synovial tissue. Osteoarthritis synovial showed high abundance of infiltrating resting mast cells, B cells memory and plasma cells. WGCNA screened 93 DEGs related to osteoarthritis immune infiltration. These genes were involved in TNF signaling pathway, IL-17 signaling pathway, response to steroid hormone, glucocorticoid and corticosteroid. Ten hub genes including MYC, JUN, DUSP1, NFKBIA, VEGFA, ATF3, IL-6, PTGS2, IL1B and SOCS3 were selected by using PPI network. Among them, four genes (MYC, JUN, DUSP1 and NFKBIA) specifically expressed in immune system were identified and clinical samples revealed consistent change of these four genes in synovial tissue retrieved from patients with osteoarthritis. CONCLUSION: A 4-gene-based diagnostic model was developed, which had well predictive performance in osteoarthritis. MYC, JUN, DUSP1 and NFKBIA might be biomarkers and potential therapeutic targets in osteoarthritis.

Transplantation efficacy of autologous bone marrow mesenchymal stem cells combined with atorvastatin for acute myocardial infarction (TEAM-AMI): rationale and design of a randomized, double-blind, placebo-controlled, multi-center, Phase II TEAM-AMI trial.

Aim: To determine the efficacy and safety of intracoronary infusion of autologous bone marrow mesenchymal stem cells (MSCINJ) in combination with intensive atorvastatin (ATV) treatment for patients with anterior ST-segment elevation myocardial infarction-elevation myocardial infarction. Patients & methods: The trial enrolls a total of 100 patients with anterior ST-elevation myocardial infarction. The subjects are randomly assigned (1:1:1:1) to receive routine ATV (20 mg/d) with placebo or MSCsINJ and intensive ATV (80 mg/d) with placebo or MSCsINJ. The primary end point is the absolute change of left ventricular ejection fraction within 12 months. The secondary end points include parameters in cardiac function, remodeling and regeneration, quality of life, biomarkers and clinical outcomes. Results & conclusion: The trial will implicate the essential of cardiac micro-environment improvement ('fertilizing') for cell-based therapy. Clinical Trial Registration: NCT03047772.