Affiliations: Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
Correspondence:
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Corresponding author: Hua Lu, Department of Orhtopaedic, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China. Tel.: +86 21 25078999; E-mail: [email protected].
Note: [1] Co-first authors.
Abstract: BACKGROUND: Osteoarthritis (OA) and osteoporosis (OS) are the most common orthopedic diseases. OBJECTIVE: To identify important genes as biomarkers for the pathogenesis of OA and OS. METHODS: Microarray data for OA and OS were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between the OA and healthy control groups and between the OS and healthy control groups were identified using the Limma software package. Overlapping hub DEGs were selected using MCC, MNC, DEGREE, and EPC. Weighted gene co-expression network analysis (WGCNA) was used to mine OA- and OS-related modules. Shared hub DEGs were identified, human microRNA disease database was used to screen microRNAs associated with OA and OS, and an miRNA-target gene network was constructed. Finally, the expression of shared hub DEGs was evaluated. RESULTS: A total of 104 overlapping DEGs were identified in both the OA and OS groups, which were mainly related to inflammatory biological processes, such as the Akt and TNF signaling pathways Forty-six hub DEGs were identified using MCC, MNC, DEGREE, and EPC modules using different algorithms. Seven modules with 392 genes that highly correlated with disease were identified in the WGCNA. Furthermore, 10 shared hub DEGs were identified between the OA and OS groups, including OGN, FAP, COL6A3, THBS4, IGFBP2, LRRC15, DDR2, RND3, EFNB2, and CD48. A network consisting of 8 shared hub DEGs and 55 miRNAs was constructed. Furthermore, CD48 was significantly upregulated in the OA and OS groups, whereas EFNB2, DR2, COL6A3, and RND3 were significantly downregulated in OA and OS. Other hub DEGs were significantly upregulated in OA and downregulated in OS. CONCLUSIONS: The ten genes may be promising biomarkers for modulating the development of both OA and OS.
