Glycosaminoglycans influence regional mechanics in young but not old Achilles tendons

Blank, Jonathon L.
Eekhoff, Jeremy D.
Soslowsky, Louis J.

¹McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania, USA,
²Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA,

Jonathon Blank completed his PhD in Mechanical Engineering at the University of Wisconsin-Madison (Madison, WI, USA) and is currently a Postdoctoral Fellow at the McKay Orthopaedic Research Laboratory at the University of Pennsylvania (Philadelphia, PA, USA). His research interests include non-invasive sensing of tendon structure-function and the role of extracellular matrix constituents in regulating tendon structure-function across age, following injury and during development of tendinopathy. Through this research he aims to enhance rehabilitation strategies and diagnosis of musculoskeletal disorders.

^*Corresponding author L. J. Soslowsky: McKay Orthopaedic Research Laboratory, University of Pennsylvania, 307A Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104-6081, USA. Email: e-mail; [email protected]

Received December 13, 2024; Accepted July 28, 2025; previously published online August 25, 2025

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Handling Editors: Paul Greenhaff & Koyal Garg

The peer review history is available in the Supporting Information section of this article (https://doi.org/10.1113/JP286609#support-information-section).

The Journal of Physiology Publish Ahead of Print, August 27, 2025. | DOI: 10.1113/JP286609

Tendons are soft musculoskeletal tissues that transfer tensile loads from muscle to bone and consist of a highly organized extracellular matrix. Highly and repetitively loaded tendons such as the Achilles tendon are more susceptible to injury, and injuries are prevalent in the older population. Glycosaminoglycans (GAGs) are long polysaccharide chains that decrease in number with age in tendon and other musculoskeletal tissues. Yet, little is known of the role of GAGs in the tensile mechanics of the ageing Achilles tendon. The objective of this study was to investigate the mechanical role of GAGs in the ageing Achilles tendon. We enzymatically digested GAGs from the Achilles tendons of young, middle-aged and old C57BL/6 mice, removing a total of 64% of GAGs from the tendon insertion and midsubstance. GAG removal did not affect viscoelastic or structural properties across age in the Achilles tendon, paired with no changes to fibril realignment. However, removal of GAGs altered regional material properties at the Achilles tendon insertion in young mice in the absence of any material property changes to the Achilles tendon midsubstance. Finally, we found no changes to regional properties at the Achilles tendon insertion or midsubstance in middle-aged or old mice. In summary, GAG content influences regional mechanical properties at the calcaneal insertion of the Achilles tendon in young mice.

Key points

The Achilles tendon is among the most commonly injured tendons, and aged tendon injuries are becoming an increasingly present societal burden.
Glycosaminoglycans decrease across age in the Achilles tendon, yet their effect on structural properties, viscoelasticity and fibre realignment is minimal.
In young Achilles tendons, glycosaminoglycans influence the elastic modulus near the calcaneal insertion, which was 60% greater following chondroitinase treatment.
These data elucidate the mechanical role of glycosaminoglycans in the healthy Achilles tendon across age.