Genome-wide transcriptional analysis of tendon tissue-related genes and pathways in the torn rotator cuff of diabetes patient.

Background: Diabetes is a major factor affecting rotator cuff tear (RCT) progression and healing. However, the underlying molecular mechanisms linking diabetes to RCT remain unclear. We aimed to investigate these mechanisms for developing targeted therapeutic strategies to improve tendon healing in diabetes patients.

Methods: Microarray analysis was used to profile differentially expressed mRNAs in RCT samples between three diabetes and three nondiabetes patients. Subsequently, Gene Ontology (GO) database, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and interaction networks for the differentially expressed genes (DEGs) were analyzed using Search Tool for the Retrieval of Interacting Genes (STRING), Cytoscape, and packages of the R computing language. All the hub genes were verified by quantitative real-time PCR (qPCR).

Results: In total, 660 DEGs were identified, including 337 upregulated genes and 323 downregulated genes. GO annotation analysis revealed that these DEGs were mainly associated with negative regulation of growth and cellular response to zinc ion in the biological process, heparin binding and cysteine-type endopeptidase activity in the molecular function, and extracellular space and plasma membrane in the cellular component. KEGG pathway analysis showed that these DEGs were mainly involved in the Staphylococcus aureus infection, mineral absorption, phagosome, asthma and influenza A. The interaction network analysis indicated that ten hub genes, including MT1H, MT1G, MT1X, MT1M, LOX, P4HA1, EGLN3, FMOD, SLC2A1, and COMP, which are functionally involved in oxidative stress response and extracellular matrix organization. The qPCR data verified that MT1H, MT1G, MT1X, MT1M, LOX, EGLN3, FMOD, and COMP were consistent with the microarray results.

Conclusions: This study preliminarily identified different gene expression patterns between diabetes and nondiabetes patients with RCT. Bioinformatic analyses suggested several altered molecular processes, including oxidative stress response and extracellular matrix organization, may contribute to tendon degeneration and impaired healing in diabetes patients. However, further studies are required to provide direct biological evidence for these associations.