Intra-articular site-specific distribution of advanced glycation end products in the shoulder of patients with diabetes mellitus having rotator cuff tears.

Abstract

Advanced glycation end products (AGEs) are compounds formed due to aging and diabetes mellitus (DM). They activate NADPH oxidase (NOX) by binding to their receptors, thereby increasing the production of reactive oxygen species (ROS), which cause oxidative stress. In this study, we investigated the effects of AGEs on the tissues of the shoulder joint (such as rotator cuff synovium, and capsule) in patients with DM having rotator cuff tears. This study included eight patients with DM who underwent surgical treatment for rotator cuff tears with contracture. The rotator cuff, synovium, and joint capsule were harvested at the time of surgery and evaluated by hematoxylin-eosin staining. Furthermore, immunostaining was used for evaluating AGEs and receptor for AGEs (RAGE), cell activity, ROS, and apoptosis. Quantitative real-time polymerase chain reaction (qPCR) was employed for the cellular evaluation of NOX, interleukins, RAGE, and collagen. The AGEs and RAGE staining as well as the ratio of ROS and apoptosis were in the following order: rotator cuff > joint capsule > synovium. In contrast, the cellular activity was significantly higher in the synovium than in the other regions. The type I collagen expression (as shown by qPCR) as well as the RAGE and NOX expressions were as follows: rotator cuff > joint capsule > synovium. Conversely, the expression of inflammatory cytokines (i.e., IL-6 and IL-1β) was higher in the synovium than in the other regions. Our study is among the first to evaluate the effects of AGEs on each tissue of the shoulder joint in patients with DM having rotator cuff tears and contractures. The accumulation of AGEs in each tissue of the shoulder joint could reveal the locations affected by DM, which can lead to a better understanding of the pathophysiology of DM-related shoulder diseases.