Drug Repurposing for Frozen Shoulder; a Bioinformatics Meta-Analysis

Objectives: Adhesive capsulitis (AC), commonly known as frozen shoulder (FS), is characterized by glenohumeral joint capsule contraction, resulting in pain, stiffness, and dysfunction. Genetic factors have been implicated in the etiology of AC, prompting a bioinformatics investigation to explore potential therapeutic targets. Methods: A systematic review of Gene Expression Omnibus (GEO) datasets was conducted using keywords related to Frozen Shoulder and Adhesive Capsulitis. The gene expression profiles from GSE۲۳۸۰۵۲, GSE۱۹۰۰۲۳, and GSE۱۴۰۷۳۱ were analyzed using the i-DEP package. Differential gene expression analysis, Gene Ontology (GO) enrichments, and drug-gene enrichments were performed through biclustering of GO pathways with the Drug.GeneSet database and dpGSEA Python application. Results: Among ۵۸,۸۲۵ genes in ۶۷ samples, ۱,۰۳۶ upregulated and ۳۷۸ downregulated genes were identified in the case-control comparison. Upregulated pathways included skeletal muscle adaptation, fiber transition, myofibril assembly, and regulation of muscle fiber development. Drug.GeneSet database analysis highlighted adenosine and its derivatives as potential therapeutic targets. Further dpGSEA analysis revealed a significant influence of adenosine on the disease. Conclusion: This study provides information about the genomic landscape of adhesive capsulitis, identifying potential therapeutic avenues centered around adenosine-related interventions. While topical or intra-articular injection of adenosine is evident in the literature, this finding should be validated through experimental studies.         Level of evidence: V

Keywords:

Adhesive capsulitis , Bioinformatics analysis , Frozen shoulder , Gene Expression Omnibus