Abstract
Background It is important to improve the understanding of the fracture healing process at the molecular levels, then to discover potential miRNA regulatory mechanisms and candidate markers. Methods Expression profiles of mRNA and miRNA were obtained from the Gene Expression Omnibus database. We performed differential analysis, enrichment analysis, protein-protein interaction (PPI) network analysis. The miRNA-mRNA network analysis was also performed. Results We identified 499 differentially expressed mRNAs (DEmRs) that were upregulated and 534 downregulated DEmRs during fracture healing. They were mainly enriched in collagen fibril organization and immune response. Using the PPI network, we screened 10 hub genes that were upregulated and 10 hub genes downregulated with the largest connectivity. We further constructed the miRNA regulatory network for hub genes and identified 13 differentially expressed miRNAs (DEmiRs) regulators. Cd19 and Col6a1 were identified as key candidate mRNAs with the largest fold change, and their DEmiR regulators were key candidate regulators. Conclusion Cd19 and Col6a1 might serve as candidate markers for fracture healing in subsequent studies. Their expression is regulated by miRNAs and is involved in collagen fibril organization and immune responses.
Highlights
Bone is a complex organ with multiple functions, including hematopoiesis, regulating and storing key minerals, protecting vital organs for life maintenance, and promoting movement
By constructing an integrated regulatory network, we identified the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways involved in these targeted mRNAs (Figure 5(b))
The results of enrichment analysis showed that these genes were mainly associated with immune response, inflammatory response, and collagen fibril organization equal to tissue repair related biological roles
Summary
Bone is a complex organ with multiple functions, including hematopoiesis, regulating and storing key minerals, protecting vital organs for life maintenance, and promoting movement. Fracture healing begins with injury-induced hematoma and inflammation, which promote condensation of periosteal, endosteal, and bone marrow mesenchymal cells, as well as differentiation into chondrocyte and osteoblast lineages [4]. We identified 499 differentially expressed mRNAs (DEmRs) that were upregulated and 534 downregulated DEmRs during fracture healing. They were mainly enriched in collagen fibril organization and immune response. We further constructed the miRNA regulatory network for hub genes and identified 13 differentially expressed miRNAs (DEmiRs) regulators. Cd19 and Col6a1 might serve as candidate markers for fracture healing in subsequent studies. Their expression is regulated by miRNAs and is involved in collagen fibril organization and immune responses
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