Influence of Frequent Corticosteroid Local Injections on the Expression of Genes and Proteins Related to Fatty Infiltration, Muscle Atrophy, Inflammation, and Fibrosis in Patients With Chronic Rotator Cuff Tears: A Pilot Study

Abstract

Background: The effect of local corticosteroid (CS) injections on rotator cuff muscles remains poorly defined, despite the significance of muscle quality as a crucial prognostic factor for patients with rotator cuff tears (RCTs). Purpose: To compare alterations in gene and protein expression patterns in the rotator cuff muscles of patients with RCTs who received frequent joint CS injections with alterations in those without a history of CS injections. Study Design: Controlled laboratory study. Methods: A total of 24 rotator cuff muscle samples with medium-sized tears from 12 patients with a frequent joint CS injection history (steroid group; 7 men and 5 women who had received ≥5 injections with at least 1 within the previous 3 months; mean age, 63.0 ± 7.2 years) and 12 age- and sex-matched control patients without a history of CS injections (no-steroid group) were acquired. Alterations in the expression of genes and proteins associated with adipogenesis, myogenesis, inflammation, and muscle fibrosis were compared between the groups using quantitative reverse transcription–polymerase chain reaction, Western blotting, and immunohistochemistry. Statistical analysis included comparison of group means using the Mann-Whitney U test, chi-square test, or Fisher exact test and logistic regression for multivariate analysis. Results: In the steroid group, the mRNA expression levels of adipogenic CCAAT/enhancer-binding protein alpha (C/EBPα; P = .008) and muscle atrophy–related genes (atrogin; P = .019) were significantly higher, and those of myogenic differentiation 1 (MyoD; P = .035), inflammatory interleukin 6 (IL-6; P = .035), and high mobility group box 1 ( P = .003) were significantly lower compared with the no-steroid group. In addition, MyoD ( P = .041) and IL-6 ( P = .026) expression were decreased in the steroid versus no-steroid group. Immunohistochemistry revealed increased expression of C/EBPα and atrogin and decreased expression of MyoD and IL-6 in the steroid versus no-steroid group. Conclusion: Patients with RCTs and a history of frequent CS injections exhibited an upregulation of adipogenic and muscle atrophy–related genes and proteins within the rotator cuff muscles and a downregulation in the expression of myogenic and inflammatory genes and proteins in the same muscles. Clinical Relevance: These altered gene and protein expressions by frequent local CS injections may cause poor outcomes in patients with RCTs.