Functional consequences of tendonitis in OA

Abstract

Purpose: Osteoarthritis and tendinopathy have many similarities. They are common in middle aged and older people and are both associated, to some extent, with individuals with a history of sporting activity and also with obese individuals. They are both diseases which show alterations in their extracellular matrix, and there are similarities in pathological features of these diseases. In both diseases, there is often little relationship between clinical and imaging features and clinical symptoms. In both diseases there have been recent interest in the role of inflammation in their onset and failure to resolve. Tendons play a fundamental role in locomotion, transferring the forces generated by our muscles to the skeleton, and thus facilitating movement. Fulfilling this role in an optimal and energy efficient manner requires a specialised structure. However, a close look at the functional role of our different tendons highlights that they require markedly varied mechanical characteristics. Energy storing tendons such as the Achilles must be highly extensible and able to store and release energy in an elastic manner. By contrast, positional tendons such as the digital extensor tendons of the hand require some dampening and the capacity to modulate muscle contraction into precise skeletal movement. While all tendons are composed of the same hierarchical collagen arrangement, these disparate functional requirements necessitate structural and compositional optimisation. Research in our group has focused on characterising structure-function mechanistic differences between tendons, and identifying the early changes which occur following fatigue injury. Methods: We have performed hierarchical biomechanical testing, compositional analysis (using proteomics, immunohistochemistry, western blotting and qPCR), and defined the early failure events following fatigue loading. This work has been performed in relevant animal species (equine) as well as in human Achilles Tendon and Anterior Tibialis Tendon. Results: With a prevalence of tendinopathy in energy storing tendons, we are particularly interested in the micromechanical specialisations facilitating more elastic, extensible behaviour in these tendons. We have shown that energy storing tendons are highly specialized, with more helically arranged fascicles that stretch less during tendon loading. Extension of energy storing tendons is also facilitated by the interfascicular matrix (IFM), which is elastin- and lubricin-rich, to facilitate sliding and recoil between fascicles during tendon loading. These specialisations lead to a less stiff, more fatigue resistant IFM in energy storing tendons, which can enable fascicle sliding and recoil during tendon loading. We have shown a loss of these structural specialisations with increasing age, leading to reduced tendon fatigue resistance, and perhaps associated with the increased risk of tendon injury with ageing. We demonstrate that fatigue loading results in specific failure within the IFM of energy-storing tendons, and is associated with upregulation of proteins associated with inflammation and matrix degradation. Subsequent to injury tendons repair by fibrochondrogenic repair and develop a tendon repair matrix which is much more cartilage like and lacks the fascicular structure which is so important for its elastic function Conclusions: In elastic energy storing tendons, which are frequently injured, a key functional anatomical specialisation is related to the IFM, which is a proteoglycan and elastin rich compartment, which is specialised to allow both fascicular sliding, and elastic recoil. With ageing there is both a stiffening and decreased fatigue resistance in this matrix, which is likely to predispose the tendon to injury. We have evidence that early fatigue damage arises within the IFM, and results in inflammatory and proteolytic changes. Tendons heal with a loss of the IFM, and formation of fibrochondrogenic scar tissue. Whilst there are some similarities to the OA process, tendon ageing and failure is a distinct process almost certainly driven by the unique function of energy-storing tendons.