Spontaneous rupture of the Achilles tendon is preceded by widespread and bilateral tendon damage and ipsilateral inflammation: A clinical and histopathologic study of 60 patients

Sakurai

et al. 2008

Arthritis & Rheumatism

Objective. To evaluate histologic, immunohistochemical, and molecular changes in tendon induced by altered strain in a large-animal model.Methods. A full-thickness partial-width laceration of the infraspinatus tendon was created in 5 sheep, while 5 sham-operated sheep were used as controls. Sheep were killed after 4 weeks, and 4 differentially stressed tendon regions (tensile or near bone attachment from overstressed or stress-deprived halves) were evaluated for histopathology, proteoglycan (PG) accumulation, and characterization of glycosaminoglycans and aggrecan catabolites. Gene expression of matrix components, enzymes, and inhibitors was analyzed by reverse transcriptase-polymerase chain reaction.Results. Histopathologic changes were detected in both overstressed and stress-deprived tensile tendon, but only in stress-deprived tendon near bone. In overstressed and stress-deprived tensile tendon, levels of keratan sulfate, chondroitin 4-sulfate, and chondroitin 6-sulfate were increased. In overstressed tensile tendon, levels of ADAMTS-generated aggrecan catabolites were increased. There was increased matrix metalloproteinase 13 (MMP-13) and decreased fibromodulin and decorin expression in all regions. Increased MMP-1, MMP-9, MMP-14, and ADAMTS-1 expression, and decreased type II collagen expression were restricted to stress-deprived tendon. In stress-deprived boneattachment regions, messenger RNA (mRNA) for aggrecan was decreased, and ADAMTS was increased. In overstressed tensile tendon, aggrecan mRNA was increased, and ADAMTS was decreased.Conclusion. The distinct molecular changes in adjacent tissue implicate altered strain rather than humoral factors in controlling abnormal tenocyte metabolism, and highlight the importance of regional sampling. Tendon abnormalities induced by increased strain are accompanied by increased aggrecan, decreased ADAMTS, and low PG expression, which may negatively impact the structural integrity of the tissue and predispose to rupture.Injuries of the shoulder due to overuse are increasingly prevalent in both the sporting arena and the workplace. Occupational injury of the shoulder is second only to neck and low back pain in the frequency of consultation by general practitioners, with the most common injury involving the rotator cuff. (1,2) The prevalence of rotator cuff conditions increases with age, from 30-50% in the seventh decade of life to a staggering 70-80% by the ninth (3,4). Although most cases are treated conservatively, many patients undergo surgical repair with a prolonged convalescence. There are no drugs to specifically treat disorders of the rotator cuff or other tendons, and many surgical repairs fail within 12 months (5). Lack of knowledge of the fundamental mechanisms that underlie tendon breakdown results in limited and inadequate management options for tendon disorders.

Section: Discussionsupporting

confidence: 85%

Modulation of aggrecan and ADAMTS expression in ovine tendinopathy induced by altered strain

Sakurai

et al. 2008

Arthritis & Rheumatism

Journal Orthopaedic Research

“…These cells are vimintin-positive, and thus likely a combination of (1) fibroblasts that are capable of both phagocytosis and collagen synthetic functions and (2) endothelial cells (neovascularization) essential to repair and remodelling. 36 This finding is in contradiction to a recent study by Cetti et al, 7 who suggested the presence of widespread bilateral and ipsilateral acute inflammation on the basis of neutrophillic infiltration in the Achilles tendons from 60 patients with a spontaneous rupture of the Achilles. These findings were noted to coexist with the features of tendon degeneration in earlier studies.…”

Section: Analysis Of Achilles Tendons In An Overuse Rat Modelmentioning

confidence: 56%

Histological analysis of achilles tendons in an overuse rat model

Glazebrook

Wright

Langman

et al. 2008

106

111

The purpose of this study was to design an animal model that induces histological changes in Achilles tendons consistent with those cited in the literature for human Achilles tendon disease. Sprague-Dawley rats were subjected to 10 degrees uphill treadmill running on a custom-designed rodent treadmill and at a speed of 17 meters per minute for 1 h, five times per week, over a 12-week treatment period. Subsequent histological analysis revealed alterations in the rat Achilles tendon that were generally consistent with those described in the literature for diseased human tendon tissues. These features include: decreased collagen fiber organization, more intense collagen staining, and increased cell nuclei numbers. Interestingly, though, immunohistochemical cell typing suggests that the observed increased cellularity does not include a significant inflammatory component but is secondary to increased numbers of endothelial cells (i.e., vascularization) and fibroblasts. These histological features likely represent a biological repair/remodeling response resulting from overuse running.

Journal of Applied Physiology

“…There is convincing evidence that the injury in energystoring tendons is associated with preceding degeneration characterized by structural and molecular changes within the tendon matrix, and this degeneration is related to both ageing and exercise (9,48,52). This observation has been supported by recent in vitro studies investigating the effects of repetitive loading on tendon matrix that show a loss of strength and upregulation of metalloproteinase activity (13, 33).…”

mentioning

confidence: 91%

“…Consequently, adaptive hypertrophy could reduce the levels of useable energy storage and thus compromise locomotor efficiency in an animal of the same weight and running at the same speed if the composition and material properties of the tissue remain the same. The mechanosensitivity of the cells from energy-storing tendons has also been shown to decrease with increasing age (22,43).There is convincing evidence that the injury in energystoring tendons is associated with preceding degeneration characterized by structural and molecular changes within the tendon matrix, and this degeneration is related to both ageing and exercise (9,48,52). This observation has been supported by recent in vitro studies investigating the effects of repetitive loading on tendon matrix that show a loss of strength and upregulation of metalloproteinase activity (13, 33).…”

mentioning

confidence: 99%

Can exercise modulate the maturation of functionally different immature tendons in the horse?

Kasashima

Takahashi²,

Birch³

et al. 2008

Tendons can be considered in two functional groups, those contributing to energetics of locomotion and those acting solely to position the limb. The energy-storing tendons in both human and equine athletes have a high frequency of injury with similar pathophysiology. In previous studies, high-intensity exercise appears to induce a disruption of the matrix rather than functional adaptation in adults. Here we explore the hypothesis that the introduction of controlled exercise during growth would result in an adaptive response without deleterious effects. Young horses were given a controlled exercise program similar to that previously shown to induce matrix changes in energy-storing tendons of skeletally mature animals. The tendons were assessed in relation to mechanical properties, molecular composition, and morphology. Results showed a significant increase in cartilage oligomeric matrix protein (COMP) in the positional tendon but not in the energy-storing tendon. Other matrix properties and mechanical properties were not significantly changed. While the imposition of high-strain-rate exercise in immature horses failed to augment the development of the energy-storing tendon over and above that induced by normal pasture exercise, it did not induce deleterious changes, supporting an earlier introduction of athletic training in horses.adaptation; hypertrophy; cartilage oligomeric matrix protein; biomechanics TENDON OVERUSE INJURIES are not only responsible for considerable loss of athletic potential in both horses (30,35,58) and humans (64), but their prevalence appears to be increasing, with a doubling in Achilles tendinopathy in recent years (26,27,34,37,38). While tendons that link muscle to bone can act merely as force transmitters to position limbs, a specific subgroup of tendons whose function is to store elastic energy contributes to efficient locomotion by acting as springs, while the associated muscle fibers serve primarily to dampen vibrations (1, 59). The Thoroughbred racehorse is a prime example of an elite animal athlete both in terms of evolution and subsequent genetic selection and conditioning. The superficial digital flexor tendon (SDFT) in the horse is an energy-storing tendon with functional and compositional similarities to the Achilles tendon in humans (7). This tendon is highly susceptible to injury, accounting for 93% of all tendon and ligament injuries in a study by Ely et al. (15) and thus can be used as a "natural" model to study tendon development and degeneration (51). The common digital extensor tendon (CDET) in contrast is a good example of a positional tendon analogous to the anterior tibialis in the human (3, 62).Over the last two decades there has been a great increase in the scientific understanding of the response of bone and muscle to mechanical loading. The mechanobiology of tendon, however, is less well understood. Effects of exercise on tendon properties have been studied in various species, including mouse (36), rat (49, 55), rabbit (61), chicken (2), guinea fowl (8), miniatur...