IGF2 expression and β-catenin levels are increased in Frozen Shoulder Syndrome

Abstract

IGF2 expression and β-catenin levels are increased in Frozen Shoulder Syndrome Abstract Purpose: Frozen Shoulder Syndrome is a brosis of the shoulder joint capsule that is clinically associated with Dupuytren's disease, a brosis of the palmar fascia. Little is known about any commonalities in the pathophysiology of these connective tissue broses. β-catenin, a protein that transactivates gene expression, and levels of IGF2 mRNA, encoding insulin-like growth factor-II, are elevated in Dupuytren's disease. e aim of this study was to determine if correlating changes in β-catenin levels and IGF2 expression are evident in Frozen Shoulder Syndrome.Methods: Tissue from patients with Frozen Shoulder Syndrome and rotator cu tear were obtained during shoulder arthroscopies. Total protein extracts were prepared from tissue aliquots and β-catenin immunoreactivity was assessed by Western immunoblotting. In parallel, primary broblasts were derived from these tissues and assessed for IGF2 expression by quantitative PCR.Results: β-catenin levels were signi cantly increased in Frozen Shoulder Syndrome relative to rotator cu tear when assessed by Western immunoblotting analyses. IGF2 mRNA levels were signi cantly increased in primary broblasts derived from frozen shoulder syndrome tissues relative to broblasts derived from rotator cu tissues. Conclusions:As in Dupuytren's disease, β-catenin levels and IGF2 expression are elevated in Frozen Shoulder Syndrome. ese ndings support the hypothesis that these connective tissue broses share a common pathophysiology. Materials and Methods Tissue collectionTissue sections were collected with approval of the Human Subjects Research Ethics Board (HSREB) at Western University from surgical specimens of patients undergoing shoulder arthroscopy for the treatment of either FSS or subacromial decompression for RCT. An arthroscopic punch was used to obtain tissue specimens from the rotator cu interval immediately adjacent to the antero-superior arthroscopic portal from patients with FSS and RCT. Representative samples of these tissues were removed at the time of surgery and immediately transported to the laboratory. e tissues were either snap frozen in liquid nitrogen for total protein extraction or processed for primary broblast derivation. Western immunoblottingTotal protein extracts were prepared from snap frozen tissue using modi ed RIPA bu er. Tissue lysate (25 μg) was subjected to Western blot analysis and β-catenin levels were assessed using an anti-β-catenin monoclonal antibody (clone 14, Transduction Laboratories, Lexington, KY). β-actin levels were assessed in parallel using an anti-β-actin antibody (Sigma, St Louis, MO) to normalize for variability in total protein loading. Antibody speci c bands were visualized using enhanced chemiluminescence (ECL) and Kodak XLS lm. Densitometry analysis was carried out using Scion Image so ware (Scion Corporation, Beta 4.0.2, Frederick, MD). Normalized measurements of β-catenin were plotted as the sample mean (β-catenin /actin) ratio ± standard error...

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