Influence of advanced glycation end products on rotator cuff.

Abstract

Most rotator cuff tears are the result of age-related degenerative changes, but the mechanisms underlying these changes have not been reported. Recently, advanced glycation end products (AGEs) have been regarded as an important factor in senescence. Therefore, we hypothesized that AGEs would have detrimental effects on rotator cuff-derived cells. In this study, we investigated the influence of AGEs on rotator cuff-derived cells in vitro and ex vivo. Rotator cuff-derived cells were obtained from human supraspinatus tendons. The cells were cultured in the following media: (1) regular medium with 500 μg/mL AGEs (High-AGEs), (2) regular medium with 100 μg/mL AGEs (Low-AGEs), and (3) regular medium alone (Control). Cell viability, secretion of vascular endothelial growth factor, and the expressions of hypoxia-inducible factor-1α, reactive oxygen species, and apoptosis were assessed after cultivation. An ex vivo tissue culture with AGEs was also performed to measure the tensile strength. Cell viability in the High-AGEs group was significantly suppressed relative to that in the Controls. The amount of vascular endothelial growth factor secretion was significantly greater in the High- and Low-AGEs groups than in the Controls. Immunofluorescence stain demonstrated enhancement of hypoxia-inducible factor-1α and reactive oxygen species expressions and cell apoptosis in the High- and Low-AGEs groups relative to that in the Controls. In ex vivo mechanical testing, tensile strength was significantly higher in the Control group than in the AGEs groups. These results indicated that AGEs caused age-related degenerative rotator cuff changes. The reduction of AGEs might prevent rotator cuff senescence-related degeneration.