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Published on: January 7, 2019
Identification of Key Chondrocyte Apoptosis-Related Genes in Osteoarthritis Based on Weighted Gene Co-Expression
Wei Wang1, Junyi Hong1, Tianyi Cao1
1Department of Orthopaedics, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Abstract:
Osteoarthritis (OA) is the primary cause of disability worldwide. Chondrocyte apoptosis has important implications for OA onset and progression. This work was designed to explore the mechanisms of chondrocyte apoptosis in OA and identify key chondrocyte apoptosis-related genes (CARGs). GSE32317 and GSE55235 datasets were acquired from the Gene Expression Omnibus (GEO) database. OA-associated module genes were determined via weighted gene co-expression network analysis (WGCNA) in GSE32317. CARGs were acquired from public databases. ClusterProfiler was employed for GO and KEGG analyses. Protein-protein interaction (PPI) network establishment was realized via the STRING database and Cytoscape, and the hub genes were screened by MCC, MNC, and DMNC algorithms of cyto-Hubba. The diagnostic values of the hub CARGs in OA in GSE55235 were verified via receiver operating characteristic (ROC) curve analysis. C28/I2 cells were stimulated with IL-1Β to establish the in vitro OA model. WGCNA identified 9,141 OA-related genes and 248 CARGs, resulting in 75 CARGs in OA. GO and KEGG analyses demonstrated that the 75 CARGs were primarily enriched in response to lipopolysaccharide, transcription regulator complex, and DNA-binding transcription factor binding, along with NF-kappa B and TNF signaling pathways. NFKB1 and ICAM1 were identified as the hub CARGs in OA through the three algorithms, which showed favorable prognostic values for OA. Notably, both bioinformatics analysis and in vitro assays revealed upregulated NFKB1 and ICAM1 expression in OA. NFKB1 and ICAM1 were the hub CARGs in OA, and might serve as diagnostic signatures and therapeutic targets for OA therapy.
Insights
This study identifies NFKB1 and ICAM1 as key genes involved in chondrocyte apoptosis in osteoarthritis (OA). These genes may serve as important diagnostic markers and therapeutic targets for OA.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Osteoarthritis (OA) is a leading global cause of disability.
- Chondrocyte apoptosis plays a critical role in the development and progression of OA.
Purpose of the Study:
- To investigate the mechanisms of chondrocyte apoptosis in OA.
- To identify key chondrocyte apoptosis-related genes (CARGs) associated with OA.
Main Methods:
- Weighted gene co-expression network analysis (WGCNA) on GEO datasets (GSE32317, GSE55235).
- Gene Ontology (GO) and KEGG pathway analyses.
- Protein-protein interaction (PPI) network construction and hub gene identification (MCC, MNC, DMNC algorithms).
- In vitro OA model using C28/I2 cells stimulated with IL-1Β.
Main Results:
- Identified 75 CARGs in OA, enriched in pathways like NF-kappa B and TNF signaling.
- NFKB1 and ICAM1 were identified as hub CARGs with favorable prognostic values for OA.
- Bioinformatics and in vitro assays confirmed upregulated NFKB1 and ICAM1 expression in OA.
Conclusions:
- NFKB1 and ICAM1 are key CARGs in osteoarthritis.
- These genes demonstrate potential as diagnostic signatures for OA.
- NFKB1 and ICAM1 may represent promising therapeutic targets for osteoarthritis treatment.
