BackgroundOsteonecrosis of femoral head (ONFH), osteoarthritis (OA) and rheumatoid arthritis (RA) are common diseases of hip joint, which will damage the joint to varying degrees, and will affect the mobility and quality of life of patients in severe cases. A better understanding of the expression of articular cartilage degeneration genes seems to be very important for further understanding the molecular mechanism of the joint action of the three diseases.Objectivethe purpose of this study was to explore the pathogenesis of cartilage injury in three diseases by analyzing the data sets of multiple gene expression groups and synthesizing the differentially expressed genes (DEGs) of ONFH, OA and RA.Methodsthe gene expression datasets of ONFH, OA and RA were obtained from Gene Expression Omnibus. Through the comprehensive analysis of multiple gene expression data sets, the common differentially expressed genes and specific DEGs in these diseases were found. Gene ontology (GO) analysis, KEGG pathway and protein-protein interaction analysis were used to investigate the functions of the altered proteins and biological pathways.ResultsA total of 59 common differentially expressed genes were obtained by GSE74089 and GSE55235 data sets, including 44 up-regulated genes and 15 down-regulated genes. GO and KEGG pathway enrichment analysis showed that DEGs concentrated on extracellular structure organization, extracellular matrix organization, fibrillar collagen trimer, platelet-derived growth factor binding, Relaxin signaling pathway, Protein digestion and absorption. Some hub genes with high interactions such as COL1A2, MMP1, VEGFC, SPP1, etc. Independent GEO dataset verification results show that these genes are consistent with the experimental results.ConclusionIn this study, bioinformatics methods were used to identify the common differential genes of ONFH, OA and RA, and to analyze the occurrence and development of cartilage degeneration or osteogenic diseases induced by them. To provide molecular basis for follow-up experiments and clinical efficacy.