Biochemical Markers of Aging (Advanced Glycation End Products) and Degeneration Are Increased in Type 3 Rotator Cuff Tendon Stumps With Increased Signal Intensity Changes on MRI

Abstract

Background: Advanced glycation end products (AGEs) are end products of protein glycation that bind to the receptor for AGEs (RAGE) and activate nicotinamide adenine dinucleotide phosphate oxidase (NOX), resulting in increased oxidative stress and rotator cuff fragility. Stump classification using the signal intensity ratio of the tendon rupture site to the deltoid muscle in the coronal view of T2-weighted fat-suppressed magnetic resonance imaging (MRI) scans is an indicator of clinical outcomes after rotator cuff repair surgery. Comparing the signal intensities of the deltoid (D) and rotator cuff tears (C), Ishitani et al. classified C/D <0.8 as type 1, 0.8 to 1.3 as type 2, and >1.3 as type 3.

Hypothesis/purpose: It was hypothesized that the oxidative stress and collagen degeneration that occur in the rotator cuff due to accumulation of AGEs can be assessed on MRI scans (stump classification). Therefore, this study aimed to compare AGE-related factors in the rotator cuff tear site tissues based on stump classification.

Study design: Descriptive laboratory study.

Methods: The authors included 30 patients (11 with type 1, 9 with type 2, and 10 with type 3; mean age, 62.3 years) who underwent surgery for complete rotator cuff tears at our hospital. Tendon tissue was harvested from the torn rotator cuff site during surgery for tissue and cell evaluation.

Results: There was no significant difference in the mean age according to stump classification. The number of patients with diabetes was significantly larger in type 3 than in the other types (P < .05). Tissue evaluation showed significantly higher expression of AGE and RAGE staining in type 3 than in the other types (~6.7-fold; P < .01). Cell evaluation showed that the expression rates of reactive oxygen species and apoptosis were significantly higher in type 3 than in the other types (~4.3-fold; P < .01). Gene expression by real-time polymerase chain reaction showed significantly higher RAGE (~5.1-fold), NOX (~5.3-fold), and IL (~3.0-fold) in type 3 than in the other types (P < .05).

Conclusion: Stump classification type 3 exhibited the highest accumulation of AGEs and the highest oxidative stress and apoptosis, suggesting a high degree of degeneration and inflammation. Imaging based on stump classification reflects the degeneration and fragility of the torn rotator cuff site.

Clinical relevance: This study provides evidence of a relationship between stump classification, which reflects rotator cuff fragility on MRI, and pathologies related to advanced glycation end products.

Keywords: advanced glycation end products; rotator cuff; stump classification.