Transcriptome analyses identify key genes and potential mechanisms in a rat model of osteoarthritis
Hui-Zi Li1,2, Hua-Ding Lu3,4
1Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China.
Background:
Osteoarthritis (OA) is one of the most common degenerative diseases of the joints worldwide, but still the pathogenesis of OA is largely unknown. The purpose of our study is to clarify key candidate genes and relevant signaling pathways in a surgical-induced OA rat model.
Methods:
The microarray raw data of GSE8077 was downloaded from GEO datasets. GeoDiver were employed to screen differentially-expressed genes (DEGs). Enrichment analyses of DEGs were performed using Metascape. Construction of protein-protein interaction (PPI) network and identification of key genes were conducted using STRING, Cytoscape v3.6.0, and Centiscape2.2. Furthermore, miRDB and Cytoscape v3.6.0 were used for visualization of miRNA-mRNA regulatory network. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for predicted miRNAs was undertaken using DIANA-miRPath v3.0.
Results:
Several DEGs (188 in comparison between OA and sham-operated group and 160 in comparison between OA and contralateral group) were identified. DEGs mainly enriched in vasculature development, regulation of cell migration, response to growth factor (Gene ontology), and ECM-receptor interaction (KEGG). Two comparison cohorts shared 79 intersection genes, and of these, Ccl2, Col4a1, Col1a1, Aldh1a3, and Itga8 were defined as the hub genes. Predicted miRNAs of seven DEGs from sub-networks mainly enriched in MAPK signaling pathway.
Conclusion:
The current study shows that some key genes and pathways, such as Ccl2, Col4a1, Col1a1, Aldh1a3, Itga8, ECM-receptor interaction, and MAPK signaling pathway may be associated with OA progression and act as potential biomarkers and therapeutic targets for OA.
Insights
This study identifies key genes like Ccl2 and Col4a1, and pathways such as ECM-receptor interaction, as potential targets for osteoarthritis (OA) treatment. These findings offer new insights into osteoarthritis pathogenesis and therapeutic strategies.
Area of Science:
- Biomedical research
- Molecular biology
- Genetics
Background:
- Osteoarthritis (OA) is a prevalent degenerative joint disease with largely unknown pathogenesis.
- Understanding OA mechanisms is crucial for developing effective treatments.
Purpose of the Study:
- To identify key genes and signaling pathways involved in osteoarthritis.
- To analyze these factors in a surgical-induced OA rat model.
Main Methods:
- Microarray data analysis of GSE8077 dataset.
- Screening of differentially-expressed genes (DEGs) using GeoDiver.
- Enrichment analyses (Gene Ontology, KEGG) and protein-protein interaction (PPI) network construction.
- MiRNA-mRNA regulatory network visualization and pathway analysis.
Main Results:
- Identified significant DEGs between OA and control groups.
- DEGs enriched in vasculature development, cell migration, and ECM-receptor interaction.
- Seven hub genes including Ccl2, Col4a1, Col1a1, Aldh1a3, and Itga8 were identified.
- MAPK signaling pathway was highlighted in miRNA-mRNA regulatory networks.
Conclusions:
- Ccl2, Col4a1, Col1a1, Aldh1a3, Itga8, ECM-receptor interaction, and MAPK signaling pathway are potentially linked to OA progression.
- These identified factors may serve as potential biomarkers and therapeutic targets for osteoarthritis.
