Comparative proteome analysis of the capsule from patients with frozen shoulder

Abstract

Background: The etiology of frozen shoulder (FS) is unclear. Accordingly, this study used a label-free quantitative shotgun proteomic approach to elucidate the pathogenesis of FS based on protein expression levels.

Methods: Tissue samples from the rotator interval (RI), middle glenohumeral ligament (MGHL), and anterior-inferior glenohumeral ligament (IGHL) were collected from 12 FSs with severe stiffness and 7 shoulders with a rotator cuff tear (RCT) as controls. Protein mixtures were digested and analyzed by nano-liquid chromatography/electrospray ionization-tandem mass spectrometry. Relative protein expression levels were calculated by the signal intensity of identified peptide ions on mass spectra. Differentially expressed proteins between FS and RCT samples were evaluated by a gene enrichment analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes.

Results: We identified 1594 proteins, 1358 of which were expressed in all 6 tissue groups. We detected more upregulated proteins in the upper (RI and MGHL) FS groups and the lower (IGHL) RCT group than in the comparative groups, respectively. Various proteins with functions in tissue repair, collagen metabolism and fibrillation, cell-cell and cell-matrix adhesion, blood coagulation, and the immune response were expressed more highly in the RI and MGHL FS groups than in the RCT group. Proteins with functions in phagocytosis, glutathione metabolism, retinoid metabolism, and cholesterol metabolism were expressed more highly in the IGHL RCT group than in the FS group.

Conclusions: The pathophysiology of FS differs between the upper and lower parts of the joint capsule. Different treatment strategies for FS may be appropriate, depending on the location.

Keywords: Frozen shoulder; adhesive capsulitis; joint capsule; ligament; pathogenesis; quantitative proteome analysis.