2017 ISAKOS Biennial Congress ePoster #304
Advanced Glycation End Products are Accumulated in Rotator Cuff Tissue with Aging
Yutaka Mifune, MD, PhD, Kobe JAPAN
Takeshi Kokubu, MD, PhD, Kobe JAPAN
Atsuyuki Inui, MD, PhD, Kobe JAPAN
Fumiaki Takase, MD, Kobe JAPAN
Yasuhiro Ueda, MD, Kobe JAPAN
Takeshi Kataoka, MD, Kobe, Hyogo JAPAN
Takashi Kurosawa, MD, Kobe JAPAN
Ryosuke Kuroda, MD, PhD, Kobe, Hyogo JAPAN
Kobe University Graduate School of Medicine, Kobe, JAPAN
FDA Status Not Applicable
Advanced Glycation End Products (AGEs) were expressed in the human RC tissues, and AGEs were accumulated in RC tissue in aged rats, resulting in decrease of mechanical strength of rotator cuff.
Most of the rotator cuff tears were considered as the result of age-related degenerative changes. However, there is no report to prove detailed mechanisms of age-related degenerative changes. Recently, advanced glycation end-products (AGEs) have been regarded as one of the notable factors for senescence. We have already reported that AGEs have detrimental effects on rotator cuff (RC) derived cells via production of reactive oxygen species (ROS) and increase of cell apoptosis in vitro study. In this study, we investigated AGEs expression in human RC tissue, and assessed the accumulation of AGEs in RC and the mechanical strength of RC in the aging process using SD rats.
Materials And Methods
Twelve patients with rotator cuff tear were enrolled, and the average age was 66.8 years old (47-81 years old). Human rotator cuff tissues were obtained from torn edges of supraspinatus tendons during arthroscopic rotator cuff repair. The tissues were sectioned, and histological assessments were performed including hematoxylin and eosin (H&E) staining, immunofluorescence stain of AGEs and AGEs receptor (RAGE). To evaluate the cell apoptosis, TUNEL staining was also performed. In the animal study, SD rats were used to investigate the accumulation of AGEs in RC tissue and the mechanical strength of RC in the aging process. We prepared 3, 6, 12 and 24 months old SD rats, and harvested supraspinatus tendon for histological assessments and infraspinatus tendon with humerus for mechanical testing. In the histological examination, H&E staining, immunofluorescence staining of AGEs and RAGE, and TUNEL staining were performed. For biomechanical test, the prepared scapula-humerus complex was mounted in a conventional tensile tester and assessed a failure load of biomechanical tensile test. Comparisons among multiple groups were made using analysis of variance (ANOVA) test followed by the Turkey's test. A value of p<0.05 was considered statistically significant.
In the histological examination using human RC tissues, the expressions of AGEs and RAGE were confirmed in all patients. Moreover, cell apoptosis were also identified in the edge of human RC tissues from all patients. In the animal study, H&E staining showed cell infiltration and disarrangement of collagen fibers in the supraspinatus tendon of 12 and 24 months old rats. Immunofluorescence staining demonstrated significant increase of AGEs and RAGE expressions in the aging process (p<0.01). The TUNEL staining also showed significant increase of cell apoptosis in the RC tendon in association with aging (p<0.01). Moreover, mechanical testing displayed the significant reduction of mechanical strength of the RC tendon in 12 and 24 months (p<0.05).
This study demonstrated that AGEs and RAGE were expressed in the human RC tissues, and that AGEs were accumulated in RC tissue in aged rats. Moreover, cell apoptosis were promoted in RC tissues of aged rats, resulting in decrease of mechanical strength of RC. Our previous report showed that AGEs have detrimental effects on RC derived cells via production of ROS and increase of cell apoptosis. These results indicated that AGEs could cause age-related degenerative changes of rotator cuff, and the reduction of AGEs might prevent rotator cuff from degeneration by senescence.