Influence of Diabetes-Induced Glycation and Oxidative Stress on the Human Rotator Cuff

• Main Authors: Tomoya Yoshikawa (Author), Yutaka Mifune (Author), Atsuyuki Inui (Author), Hanako Nishimoto (Author), Kohei Yamaura (Author), Shintaro Mukohara (Author), Issei Shinohara (Author), Ryosuke Kuroda (Author)
• Format: Book
• Published: MDPI AG, 2022-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antiox11040743; 2076-3921
• Keywords: rotator cuff; glycation reaction; advanced glycation end-products; oxidative stress; reactive oxygen species; diabetes; Therapeutics. Pharmacology; RM1-950
• Source: Antioxidants, Vol 11, Iss 4, p 743 (2022)

Most shoulder rotator cuff tears (RCTs) are caused by non-traumatic age-related rotator cuff degeneration, of which hyperglycemia is a risk factor due to its glycation reaction and oxidative stress. We aimed to identify the influence of diabetes-induced glycation and oxidative stress in patients with non-traumatic shoulder RCTs. Twenty patients, aged over 50 years, with non-traumatic shoulder RCTs participated in this study. Patients with a history of diabetes mellitus or preoperative HbA1c ≥ 6.5% were assigned to the diabetic group (<i>n</i> = 10), and the rest to the non-diabetic group (<i>n</i> = 10). Cell proliferation; expression of genes related to oxidative stress, glycation reaction, inflammation, and collagen; intracellular reactive oxygen species (ROS) levels; and apoptosis rates were analyzed. The diabetic group had significantly lower cell proliferation than the non-diabetic group. In the diabetic group, the mRNA expression levels of <i>NOX1</i>, <i>NOX4</i>, <i>IL6</i>, <i>RAGE</i>, type III collagen, <i>MMP2</i>, <i>TIMP1</i>, and <i>TIMP2</i> were significantly higher; type I collagen expression was significantly lower; and the rate of ROS-positive cells and apoptotic cells, as well as the expression of advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE), was significantly higher. In conclusion, hyperglycemia caused by diabetes mellitus increased AGE and RAGE expression, and led to increased NOX expression, ROS production, and apoptosis in the human rotator cuff. This provides scope to find a preventive treatment for non-traumatic RCTs by inhibiting glycation and oxidative stress.