As high incidences of tendinopathies are observed particularly in those who intensively use their tendons, we assume that pathological changes are caused, at least partially, by mechanical overload. This has led to the so-called overload hypothesis, explaining the development of tendinopathies by structural failure resulting from excessive load. At the same time, tendon loading is an important part in tendon rehabilitation. Currently, exercise treatment approaches such as eccentric training or heavy load resistance training are widely applied in tendinopathy rehabilitation, with good clinical results such as an improvement in function and a reduction in pain. Particularly those rehabilitative approaches which impose high strains on the tendon may induce an adaptation of the tendon's mechanical properties such as increased tendon stiffness. An increased tendon stiffness is often interpreted as desirable, as it may protect the tendon from overloading and thus prevent future strain injuries. However, the tendinopathic tendon is not necessarily less stiff than the tendon in the contralateral leg and an improvement in tendon stiffness is not necessarily accompanied by an improvement in tendon pain or function. In addition, metabolic factors, resulting e.g. in low-level systemic inflammation, may contribute to pathological tendon tissue changes and are not necessarily affected by an exercise program, while nutritional interventions or dietary supplements may potentially affect tendon cell metabolism. Indeed, dietary supplements have been introduced as an additional therapeutic approach in the treatment of tendinopathies in recent years, and their positive curative effects have been reported for both the general population and athletes. In the management of tendinopathies, it may thus be advisable if therapeutic approaches aim to address both tendon mechanics and tendon metabolism for better treatment effectiveness and a sustainable improvement in pain and function.

Introduction

The exact mechanisms leading to tendinopathies and tendon ruptures remain poorly understood while their occurrence is clearly associated with exercise. Overloading is thought to be a major factor contributing to the development of tendon pathologies. However, as animal studies have shown, heavy loading alone won't cause tendinopathies. It has been speculated, that malfunctioning adaptation or healing processes might be involved, triggering tendon tissue degeneration. By analysing the expression of the entirety of degrading enzymes (degradome) in pathological and non-pathological, strained and non-strained tendon tissue, the aim of this study was to identify common or opposite patterns in gene regulation. This approach may generate new targets for future studies.

Summary Statement

We have shown that integrin mRNA expression is regulated by the application of mechanical load. This indicates that mechanical loading may modify cell sensitivity to perceive further load through increased interaction with the ECM.

Most cases of tendinopathy are believed to be overuse injuries rather than the result of a chronic event. The investigation of the fatigue properties of tendon is therefore of critical importance. This work considered the cyclic stress-relaxation and creep behaviour of two contrasting bovine tendon types – the largely postional digital extensor and the more energy storing deep digital flexor tendon. Fascicles were cyclically loaded (1Hz), to 1800 cycles of stress relaxation or to failure in creep, stopping some tests at 300, 900 or 1200 cycles to perform quasi-static failure tests or confocal imaging using a highly concentrated Acridine Orange solution. Creep tests were cycled to 60% of the ultimate tensile strength (UTS), while for stress relaxation, cyclic deformation to the strain associated with 60% UTS was used. Flexor tendon fascicles were found to exhibit reduced stress relaxation at all time points compared to the extensor fascicles and also showed an increase in the mean cycles to failure during creep testing. Evidence of fatigue damage was clear in the confocal images with breakdown of the collagen fibre alignment evident from 300 cycles; however it appears that some damage could occur without effect on the UTS of the fascicle. Despite what appears to be superior fatigue resistance in the flexor tendon fascicles, the matrix damage, certainly at early time points, appeared visually to be as severe as that observed with the extensor tendon fascicles.