Background: Modulation of tendon healing remains a challenge because of our limited understanding of the tendon repair process. Therefore, we performed the present study to provide a global perspective of the gene expression profiles of tendons after injury and identify the molecular signals driving the tendon repair process. Results: The gene expression profiles of flexor digitorum profundus tendons in a chicken model were assayed on day 3, weeks 1, 2, 4, and 6 after injury using the Affymetrix microarray system. Principal component analysis (PCA) and hierarchical cluster analysis of the differentially expressed genes showed 3 distinct clusters corresponding to different phases of the tendon healing period. Gene ontology (GO) analysis identified regulation of cell proliferation and cell adhesion as the most enriched biological processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the cytokine-cytokine receptor interaction and extracellular matrix (ECM)-receptor interaction pathways were the most impacted. Weighted gene co-expression network analysis (WGCNA) demonstrated 4 distinct patterns of gene expressions during tendon healing. Cell adhesion and ECM activities were mainly associated with genes with drastic increase in expression 6 weeks after injury. The protein–protein interaction (PPI) networks were constructed to identify the key signaling pathways and hub genes involved. Conclusions: The comprehensive analysis of the biological functions and interactions of the genes differentially expressed during tendon healing provides a valuable resource to understand the molecular mechanisms underlying tendon healing and to predict regulatory targets for the genetic engineering of tendon repair.

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