Abstract
Pentosidine, a biomarker for advanced glycation end products (AGEs), accumulates in vessels, kidney, skin, and bone and induces serious pathological conditions in diabetic patients. However, the relationship between AGE deposition and biomechanical weakness in tendons has not been elucidated. We hypothesized that diabetic status might induce excessive pentosidine deposition in tendon tissue and that accumulated pentosidine might modify the biomechanical properties of the diabetic tendon. In this study, we assessed the effect of pentosidine on cellular viability, senescence, and gene expression of type I/III collagens in NIH3T3 fibroblasts. Pentosidine deposition and the biomechanical properties of diabetic Achilles tendon were investigated using a diabetic rat model. Pentosidine induced cellular senescence of NIH3T3 fibroblasts in a dose-dependent manner without affecting cellular viability. Moreover, pentosidine decreased gene expression of type I/III collagens in NIH3T3 fibroblasts. Diabetic rats showed a higher level of pentosidine deposition in their Achilles tendons compared with that in normal rats. In addition, the toughness and ultimate stress of the Achilles tendon were lower in diabetic rats. Our results suggest that pentosidine may induce cellular senescence and inhibit collagen synthesis in tendon fibroblasts. Moreover the accumulated pentosidine may alter the biomechanical properties of the Achilles tendon in the diabetic rats. Hence the suppressed collagen synthesis may cause the deterioration of the tendon mechanical properties. These phenomena might be one of the reasons of the tendon deterioration in the diabetic patients.
Highlights
In diabetic patients, advanced glycation end products (AGEs) accumulate in the vessels, kidney, skin, bones, and other tissues [1,2,3,4,5,6] and results in diabetic vascular complications such as retinopathy [5,6], nephropathy [2], and neuropathy [7]
Pentosidine administration had no effect on the cell viability of NIH3T3 fibroblasts (Figure 2A)
The results of this study showed that the Achilles tendons of Otsuka Long-Evans Tokushima fatty (OLETF) rats, which are animal models of type II diabetes, had a greater level of pentosidine deposition compared with that in the Achilles tendons of Long-Evans Tokushima Otsuka (LETO) rats
Summary
In diabetic patients, advanced glycation end products (AGEs) accumulate in the vessels, kidney, skin, bones, and other tissues [1,2,3,4,5,6] and results in diabetic vascular complications such as retinopathy [5,6], nephropathy [2], and neuropathy [7]. Osteoporosis is caused by the deposition of AGEs in bone tissue [3,4,8]. The effect of AGE deposition on tendon tissue has not been fully investigated. Several authors have studied the effect of AGEs on cultured cells [9,10,11,12,13]. AGEs induce fibroblast apoptosis through the activation of reactive oxygen species, mitogen-activating protein kinase, and forkhead box protein O1 transcription factor [12]. These studies indicate that AGEs induce inflammation and apoptosis by deteriorating the viability of fibroblasts
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