Structure-function specialisation of the interfascicular matrix in the human achilles tendon

Abstract

Tendon consists of highly aligned collagen-rich fascicles surrounded by interfascicular matrix (IFM). Some tendons act as energy stores to improve locomotion efficiency, but such tendons commonly obtain debilitating injuries. In equine tendons, energy storing is achieved primarily through specialisation of the IFM. However, no studies have investigated IFM structure-function specialisation in human tendons. Here, we compare the human positional anterior tibial tendon and energy storing Achilles tendons, testing the hypothesis that the Achilles tendon IFM has specialised composition and mechanical properties, which are lost with ageing. Data demonstrate IFM specialisation in the energy storing Achilles, with greater elasticity and fatigue resistance than in the positional anterior tibial tendon. With ageing, alterations occur predominantly to the proteome of the Achilles IFM, which are likely responsible for the observed trends towards decreased fatigue resistance. Knowledge of these key energy storing specialisations and their changes with ageing offers crucial insight towards developing treatments for tendinopathy. Statement of significance Developing effective therapeutics or preventative measures for tendon injury necessitates the understanding of healthy tendon function and mechanics. By establishing structure-function relationships in human tendon and determining how these are affected by ageing, potential targets for therapeutics can be identified. In this study, we have used a combination of mechanical testing, immunolabelling and proteomics analysis to study structure-function specialisations in human tendon. We demonstrate that the interfascicular matrix is specialised for energy storing in the Achilles tendon, and that its proteome is altered with ageing, which is likely responsible for the observed trends towards decreased fatigue resistance. Knowledge of these key energy storing specialisations and their changes with ageing offers crucial insight towards developing treatments and preventative approaches for tendinopathy.

CD146 Delineates an Interfascicular Cell Sub-Population in Tendon That Is Recruited during Injury through Its Ligand Laminin-α4

“…Previous studies have implicated that TGF-β signalling has important roles in tendon development, homeostasis and injury, with activation of TGF-β in the IFM during development. This is predicted to result in the synthesis of major ECM proteins [ 74 , 75 , 76 ], and the dysregulation of TGF-β signalling is implicated in the ageing of the human Achilles tendon [ 77 ]. These results are supported by our study, with pathway analysis of DE serum miRNAs predicting upstream regulation by TGF-β signalling.…”

The impact of age-related increase in passive muscle stiffness on simulated upper limb reaching

“…Moreover, the increase in passive force could occur with, and be partially caused by, age-related reduction in optimal muscle lengths [ 29 ]. Tendons, which affect force transmission and a muscle’s length and velocity trajectory during movements, may also undergo age-related structural changes [ 57 ], although the changes in tendon stiffness can be insignificant in the upper limbs [ 58 ]. Due to the nonlinearity of the arm model, the consequences of multiple such changes are hard to predict, and hence remain a subject for further study.…”

Guidelines for ex vivo mechanical testing of tendon

“…Increased collagen organization, increased collagen packing (higher collagen area fraction) 73,74 Higher tissue modulus Lower tissue diffusivity/convective transport Increased enzymatic collagen crosslinking [75][76][77][78] Higher tissue strength and modulus Lower molecular/tissue creep Increased complexity of meso-/macro-scale hierarchy (e.g., interfascicular matrix, paratenon) [79][80][81][82] Lower rate of muscle force development (decreased maximum muscle power) answer a study's question, while in other cases (e.g., quantifying the effect of a genetic or compositional perturbation), complex viscoelastic modeling may be necessary.…”