Abstract

The aim of this study was to mine cartilage damage and regeneration-related biomarkers and identify the gene regulatory networks of cartilage damage. A gene expression data set (GSE129147) containing damaged and control samples collected from the knee of the same patients was employed. R package limma was used to identify differentially expressed genes (DEGs), and clusterProfiler was performed for the GO and KEGG functional enrichment analysis. Cytoscape plug-ins of CytoHubba and MCODE were applied to investigate protein-protein interaction (PPI) network, modules, and hub genes. We identified 422 DEGs that were involved in skeletal system development, bone development, ossification, mesenchyme development, mesenchymal cell differentiation, connective tissue development, osteoblast differentiation, and extracellular matrix. We dug out 30 hub genes, identified three PPI modules, and constructed a miRNA regulatory network for DEGs. The miRNAs of the DEGs were predicted by miRNet, and the miRNA-mRNA network displayed some important miRNAs such as miR-335-5p, miR-92a-3p, and miR-98-5p. Collectively, these results have the potential to clarify the mechanism of cartilage damage and to assist us in discovering the damage and repair-related biomarkers.

Highlights

  • In the joint, the surface of the connecting bone is covered with a layer of articular cartilage

  • Functional enrichment of GO terms showed that these differentially expressed genes (DEGs) were involved in the extracellular matrix (ECM), skeletal system development, bone development, ossification, mesenchyme development, mesenchymal cell differentiation, connective tissue development, and osteoblast differentiation

  • The KEGG pathway enrichment revealed the DEGs were engaged in the PI3K-Akt signaling pathway, ECM-receptor interaction, and rheumatoid arthritis (Fig. 2)

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Summary

Introduction

The surface of the connecting bone is covered with a layer of articular cartilage. Because of the lack of selfregeneration for the damaged cartilage, it is essential to understand the molecular mechanisms in the progression of cartilage damage [2,3]. Some progress has been made in understanding the mechanisms of cartilage matrix degradation, and has promoted the progressive remodeling of the affected joints [4,5]. The aim of this study was to mine cartilage damage and regeneration-related biomarkers and identify the gene regulatory networks of cartilage damage. Results: We identified 422 DEGs that were involved in skeletal system development, bone development, ossification, mesenchyme development, mesenchymal cell differentiation, connective tissue development, osteoblast differentiation, and extracellular matrix. Conclusions: Collectively, these results have the potential to clarify the mechanism of cartilage damage and to assist us in discovering the damage and repair-related biomarkers

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