Drug Repurposing for Frozen Shoulder; a Bioinformatics Meta-Analysis

Document Type : RESEARCH PAPER

Authors

1 Orthopedic Research Center, Shahid Kamyab Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of orthopaedic surgery, Dow University of health sciences, civil hospital, karachi, Pakistan

3 Sub-Department of Operations and Analytics, Department of Management, Faculty of Environment, Science and Economy, University of Exeter Exeter, UK

4 Shahid Sadoughi University of Medical Sciences, Yazd, Iran

5 5 Department of Family Medicine, Hamdard Health, Chicago, IL United States

6 Department of Orthopaedic surgery, Children's health Ireland hospital, Dublin, Ireland

7 Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran

8 Department of Surgery, School of Medicine, Peymanie Hospital, Jahrom University of Medical Sciences, Iran

9 Department of Orthopedics, School of Medicine, Peymanie Hospital, Jahrom University of Medical Sciences, Iran

10 Department of Anesthesiology and Critical Care, School of Medicine, 5th Azar Hospital, Sayyad Shirazi Hospital, Golestan University of Medical Sciences, Golestan, Iran

10.22038/abjs.2025.78385.3609

Abstract

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 GSE238052, GSE190023, and GSE140731 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 58,825 genes in 67 samples, 1,036 upregulated and 378 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

Main Subjects

References

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The Archives of Bone and Joint Surgery
Volume 13, Issue 11
November 2025
Pages 704-710

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History

  • Receive Date: 09 March 2024
  • Revise Date: 25 May 2025
  • Accept Date: 26 February 2025

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