Studies on the pathogenesis of equine tendonitis following collagenase injury

Williams, I.F.; McCullagh, K.G.; Goodship, Allen E.; Silver, Ian A.

doi:10.1016/s0034-5288(18)31954-4

Cited by 102 publications

(89 citation statements)

References 8 publications

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“…Our findings were consistent with other studies performed in large animals, in which the severity of the pathology was related to the amount of the injected collagenase [33]. The morphological changes—especially occurring at day 15—resembled the histological appearance of tendinopathy in humans.…”

Section: Discussionsupporting

confidence: 91%

Dose-Related and Time-Dependent Development of Collagenase-Induced Tendinopathy in Rats

et al. 2016

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Tendinopathy is a big burden in clinics and it represents 45% of musculoskeletal lesions. Despite the relevant social impact, both pathogenesis and development of the tendinopathy are still under-investigated, thus limiting the therapeutic advancement in this field. The purpose of this study was to evaluate the dose-dependent and time-related tissue-level changes occurring in a collagenase-induced tendinopathy in rat Achilles tendons, in order to establish a standardized model for future pre-clinical studies. With this purpose, 40 Sprague Dawley rats were randomly divided into two groups, treated by injecting collagenase type I within the Achilles tendon at 1 mg/mL (low dose) or 3 mg/mL (high dose). Tendon explants were histologically evaluated at 3, 7, 15, 30 and 45 days. Our results revealed that both the collagenase doses induced a disorganization of collagen fibers and increased the number of rounded resident cells. In particular, the high dose treatment determined a greater neovascularization and fatty degeneration with respect to the lower dose. These changes were found to be time-dependent and to resemble the features of human tendinopathy. Indeed, in our series, the acute phase occurred from day 3 to day 15, and then progressed towards the proliferative phase from day 30 to day 45 displaying a degenerative appearance associated with a very precocious and mild remodeling process. The model represents a good balance between similarity with histological features of human tendinopathy and feasibility, in terms of tendon size to create lesions and costs when compared to other animal models. Moreover, this model could contribute to improve the knowledge in this field, and it could be useful to properly design further pre-clinical studies to test innovative treatments for tendinopathy.

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Section: Discussionsupporting

confidence: 91%

Dose-Related and Time-Dependent Development of Collagenase-Induced Tendinopathy in Rats

et al. 2016

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“…This is reflected by previous studies which have used a wide range of species as models for tendon injuries, including non-human primates, horses, goats, dogs, rabbits, rats and mice. [12][13][14][15][16][17][18][19][20][21][22][23][24] From a translational standpoint, non-human primates represent the most ideal species to use in tendon research as they are the closest to humans in terms of anatomy and physiology. However, their use is limited by ethical considerations and a lack of availability which results in extraordinary high costs (table 1).…”

Section: Selection Of Appropriate Speciesmentioning

confidence: 99%

Animal models for the study of tendinopathy

2006

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Tendinopathy is a common and significant clinical problem characterised by activity-related pain, focal tendon tenderness and intratendinous imaging changes. Recent histopathological studies have indicated the underlying pathology to be one of tendinosis (degeneration) as opposed to tendinitis (inflammation). Relatively little is known about tendinosis and its pathogenesis. Contributing to this is an absence of validated animal models of the pathology. Animal models of tendinosis represent potential efficient and effective means of furthering our understanding of human tendinopathy and its underlying pathology. By selecting an appropriate species and introducing known risk factors for tendinopathy in humans, it is possible to develop tendon changes in animal models that are consistent with the human condition. This paper overviews the role of animal models in tendinopathy research by discussing the benefits and development of animal models of tendinosis, highlighting potential outcome measures that may be used in animal tendon research, and reviewing current animal models of tendinosis. It is hoped that with further development of animal models of tendinosis, new strategies for the prevention and treatment of tendinopathy in humans will be generated.

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“…15 16 It is known that collagenase results in rapid dissolution of fibers, cell necrosis, and vascular damage and inflammation, which mimic many aspects of naturally occurring traumatic injuries. 17 In this paper, structural and property changes in collagen fibrils with collagenase-induced Achilles tendon injury were observed using AFM.…”

Section: Introductionmentioning

confidence: 99%

Changes in Collagen Fibril Pattern and Adhesion Force with Collagenase-Induced Injury in Rat Achilles Tendon Observed via AFM

Lee¹,

Choi²,

Chon³

et al. 2011

j nanosci nanotechnol

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The Achilles tendon consists mainly of type I collagen fibers that contain collagen fibrils. When the Achilles tendon is injured, it is inflamed. The collagenase-induced model has been widely used to study tendinitis. The major advantages of atomic force microscopy (AFM) over conventional optical and electron microscopy for bio-imaging include its non-requirement of a special coating and vacuum, and its capability to perform imaging in all environments. AFM force-distance measurements have become a fundamental tool in the fields of surface chemistry, biochemistry and materials science. Therefore, the changes in the ultrastructure and adhesion force of the collagen fibrils on the Achilles tendons of rats with Achilles tendinitis were observed using AFM. The changes in the structure of the Achilles tendons were evaluated based on the diameter and D-banding of the collagen fibrils. Collagenase-induced Achilles tendinitis was induced with the injection of 30 microl crude collagenase into 7-week-old male Sprague-Dawley rats. The animals were each sacrificed on the first, second, third, fifth and seventh day after the collagenase injection. The normal and injured Achilles tendons were fixed in 4% buffered formalin and dehydrated with increasing concentrations of ethanol. AFM was performed using the non-contact mode at the resolution of 512 x 512 pixels, with a scan speed of 0.8 line/sec. The adhesion force was measured via the force-distance curve that resulted from the interactions between the AFM tip and the collagen fibril sample using the contact mode. The diameter of the collagen fibrils in the Achilles tendons significantly decreased (p < 0.05) after the collagenase injection, and the pattern of the D-banding of the collagen fibrils was similar to that of the diameter changes. The adhesion force decreased until the fifth day after the collagenase injection, but increased on the seventh day after the collagenase injection (p < 0.0001).

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Studies on the pathogenesis of equine tendonitis following collagenase injury

Cited by 102 publications

References 8 publications

Dose-Related and Time-Dependent Development of Collagenase-Induced Tendinopathy in Rats

Dose-Related and Time-Dependent Development of Collagenase-Induced Tendinopathy in Rats

Animal models for the study of tendinopathy

Changes in Collagen Fibril Pattern and Adhesion Force with Collagenase-Induced Injury in Rat Achilles Tendon Observed via AFM

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