Identification of Biomarkers That Modulate Osteogenic Differentiation in Mesenchymal Stem Cells Related to Inflammation and Immunity: A Bioinformatics-Based Comprehensive Study.

Abstract

Background: Inducing mesenchymal stem cells (MSCs) osteogenesis may be beneficial in a number of clinical applications. The aim of this study is to identify key novel biomarkers of this process and to analyze the possible regulatory effects on inflammation and immunity. Results: Seven datasets (GSE159137, GSE159138, GSE114117, GSE88865, GSE153829, GSE63754, GSE73087) were obtained from the Gene Expression Omnibus database and were assigned to either the training or the validation dataset. The least absolute shrinkage and selection operator (LASSO) logistic regression model was applied to the training data to select biomarkers of osteogenesis, which were then confirmed using the validation dataset. FK506 binding protein 5 (FKBP5), insulin-like growth factor binding protein (IGFBP2), prostaglandin E receptor 2 (PTGER2), SAM domain and HD domain-containing protein 1 (SAMHD1), and transmembrane tetratricopeptide 1 (TMTC1) were highlighted as potential biomarkers. In addition, the differential expressions of immunity and inflammation-related genes were examined and their correlations with the five identified biomarkers were analyzed. The results from performing RT-qPCR and Western blots confirmed that the levels of each of these biomarkers were all significantly increased following osteogenic differentiation of MSCs. Conclusions: Our results identify five biomarkers related to MSCs osteogenesis and allow us to identify their potential roles in immunoregulation and inflammation. Each biomarker was verified by in vitro experiments.