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Characterizing hedgehog pathway features in senescence associated osteoarthritis through Integrative multi-omics and
Tao Wang1, Zhengrui Li2, Shijian Zhao3
1Department of Orthopedic Joint, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Frontiers in Genetics
|March 6, 2024
Summary
The Hedgehog pathway is activated in osteoarthritis (OA), driving inflammation and extracellular matrix changes. Identifying key Hedgehog-associated genes offers new insights into OA pathogenesis and immune regulation.
Area of Science:
- Genomics and Bioinformatics
- Molecular Biology
- Immunology
Background:
- Osteoarthritis (OA) is characterized by senescence and inflammation, yet the role of the Hedgehog signaling pathway remains unclear.
- Understanding the molecular mechanisms underlying OA pathogenesis is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To identify Hedgehog-associated genes involved in Osteoarthritis (OA) using integrated bulk and single-cell RNA sequencing (scRNA-seq).
- To investigate the impact of these genes on OA pathogenesis, including pathway activity, immune infiltration, and cellular communication.
Main Methods:
- Integrated analysis of multiple bulk RNA-seq datasets and one scRNA-seq dataset for OA.
- Machine learning algorithms for identifying key Hedgehog-associated genes and validating predictive models.
- Gene Set Enrichment Analysis (GSEA), Cibersort, MCP-counter, ConsensusClusterPlus, Weighted Gene Co-expression Network Analysis (WGCNA), and Real-time PCR for comprehensive molecular and cellular characterization.
Main Results:
- Significantly enhanced Hedgehog pathway activity was observed in OA, with nine key Hedgehog-associated genes identified.
- Predictive models demonstrated strong capabilities, and GSEA linked these genes to lysosomal functions.
- Two distinct hedgehog-related subgroups were identified, with one showing upregulated Hedgehog activity and inflammatory pathways; scRNA-seq revealed pathway upregulation, temporal gene expression changes, and chondrocyte-macrophage communication.
Conclusions:
- The Hedgehog pathway is significantly activated in OA, correlating with extracellular matrix and collagen proteins.
- This pathway plays a critical role in regulating immune cells and inflammatory responses within the OA microenvironment.
- Identified Hedgehog-associated genes and pathways provide potential targets for future OA therapeutic interventions.
