Human Achilles tendon mechanical behavior is more strongly related to collagen disorganization than advanced glycation end-products content

Jennifer A Zellers,Mary K Hastings,Jeremy D Eekhoff,Remy E Walk,Spencer P Lake,Simon Y Tang

doi:10.1038/s41598-021-03574-4

Jennifer A Zellers, Mary K Hastings + Show 4 more

Open Access

https://doi.org/10.1038/s41598-021-03574-4

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Abstract

Diabetes is associated with impaired tendon homeostasis and subsequent tendon dysfunction, but the mechanisms underlying these associations is unclear. Advanced glycation end-products (AGEs) accumulate with diabetes and have been suggested to alter tendon function. In vivo imaging in humans has suggested collagen disorganization is more frequent in individuals with diabetes, which could also impair tendon mechanical function. The purpose of this study was to examine relationships between tendon tensile mechanics in human Achilles tendon with accumulation of advanced glycation end-products and collagen disorganization. Achilles tendon specimens (n = 16) were collected from individuals undergoing lower extremity amputation or from autopsy. Tendons were tensile tested with simultaneous quantitative polarized light imaging to assess collagen organization, after which AGEs content was assessed using a fluorescence assay. Moderate to strong relationships were observed between measures of collagen organization and tendon tensile mechanics (range of correlation coefficients: 0.570–0.727), whereas no statistically significant relationships were observed between AGEs content and mechanical parameters (range of correlation coefficients: 0.020–0.210). Results suggest that the relationship between AGEs content and tendon tensile mechanics may be masked by multifactorial collagen disorganization at larger length scales (i.e., the fascicle level).

Highlights

Diabetes is associated with impaired tendon homeostasis and subsequent tendon dysfunction, but the mechanisms underlying these associations is unclear
We observed moderate to strong relationships between measures of collagen organization and tendon tensile mechanics, whereas no statistically significant relationships were observed between Advanced glycation end-products (AGEs) content and mechanical parameters
Relationships between AGEs content and tendon tensile mechanics may be present based on prior study findings[12,13], but the results of this study suggest that collagen disorganization is the dominant mechanistic predictor of tensile behavior

Summary

Introduction

Diabetes is associated with impaired tendon homeostasis and subsequent tendon dysfunction, but the mechanisms underlying these associations is unclear. Advanced glycation end-products (AGEs) accumulate with diabetes and have been suggested to alter tendon function. In vivo imaging in humans has suggested collagen disorganization is more frequent in individuals with diabetes, which could impair tendon mechanical function. The purpose of this study was to examine relationships between tendon tensile mechanics in human Achilles tendon with accumulation of advanced glycation end-products and collagen disorganization. Results suggest that the relationship between AGEs content and tendon tensile mechanics may be masked by multifactorial collagen disorganization at larger length scales (i.e., the fascicle level). Characterized by impaired glycemic control, diabetes is associated with a three times greater risk of tendon injury[3], and stiffening and functional shortening of the Achilles tendon is reported to contribute to abnormal walking mechanics, plantar ulceration, and limb loss[4,5,6,7,8]. As an example, unorganized collagen reduces tendon stiffness in degenerative conditions like tendinosis[41,42,43,44,45]

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