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A growing interest in the mechanisms that govern tendon healing has resulted in the develop-ment of tools, such as the tamoxifen-inducible mouse knockdown model, to address these questions. However, tamoxifen is a selective estrogen receptor modulator and may interfere with the tendon healing process. The objective of this study was to evaluate the effects of tamoxifen on post-injury tendon mechanics in wild-type mice.The mice underwent treatment at the time of injury using an established mouse injury model and the injured tendons were evaluated 3 weeks post-injury. The treatment contained tamoxifen suspended in corn oil and was compared to a treatment with only corn oil, as well as mice with no treatment. Tendons were evaluated by measuring the quasi-static and viscoelastic mechanics, collagen fiber realignment, cellularity, and nuclear morphology.Mechanical testing of the tendons post-injury revealed no changes to viscoelastic mechanics, quasi-static mechanics, or collagen realignment during loading after tamoxifen treatment with the dosage regimen utilized (three daily injections of 4.5 mg/40 g body weight). Additionally, histological analysis revealed no changes to cellularity or cell nuclear shape.Overall, this study revealed that tamoxifen treatment at the time of tendon injury did not result in changes to tendon mechanics or the histological parameters at 3 weeks post-injury.

Decorin and biglycan are two small leucine-rich proteoglycans (SLRPs) that regulate collagen fibrillogenesis and extracellular matrix assembly in tendon. The objective of this study was to determine the individual roles of these molecules in maintaining the structural and mechanical properties of tendon during homeostasis in mature mice. We hypothesized that knockdown of decorin in mature tendons would result in detrimental changes to tendon structure and mechanics while knockdown of biglycan would have a minor effect on these parameters. To achieve this objective, we created tamoxifen-inducible mouse knockdown models targeting decorin or biglycan inactivation. This enables the evaluation of the roles of these SLRPs in mature tendon without the abnormal tendon development caused by conventional knockout models. Contrary to our hypothesis, knockdown of decorin resulted in minor alterations to tendon structure and no changes to mechanics while knockdown of biglycan resulted in broad changes to tendon structure and mechanics. Specifically, knockdown of biglycan resulted in reduced insertion modulus, maximum stress, dynamic modulus, stress relaxation, and increased collagen fiber realignment during loading. Knockdown of decorin and biglycan produced similar changes to tendon microstructure by increasing the collagen fibril diameter relative to wild-type controls. Biglycan knockdown also decreased the cell nuclear aspect ratio, indicating a more spindle-like nuclear shape. Overall, the extensive changes to tendon structure and mechanics after knockdown of biglycan, but not decorin, provides evidence that biglycan plays a major role in the maintenance of tendon structure and mechanics in mature mice during homeostasis.

A rotator cuff tear is a common injury in athletes and workers who repeatedly perform overhead movements, and it is not uncommon for this demographic to return to activity shortly after treatment. A biceps tenotomy is often performed in the presence of a rotator cuff tear to help reduce pain and improve joint function. However, the effect of this procedure on the surrounding tissues in the glenohumeral joint is unknown. Therefore, the purpose of this study was to investigate the effect of a biceps tenotomy in the presence of a supraspinatus rotator cuff tear followed by overuse activity on ambulatory function and mechanical and histologic properties of the remaining rotator cuff tendons and glenoid cartilage. 46 rats underwent 4weeks of overuse activity to create a tendinopathic condition, then were randomized into two groups: unilateral detachment of the supraspinatus tendon or detachment of the supraspinatus and long head of the biceps tendons. Ambulatory measurements were performed throughout the 8weeks prior to euthanasia, followed by analysis of the properties of the remaining intact tendons and glenoid cartilage. Results demonstrate that shoulder function was not effected in the biceps tenotomy group. However, the intact tendons and glenoid cartilage showed altered mechanical and histologic properties. This study provides evidence from an animal model that does not support the use of tenotomy in the presence of a supraspinatus tendon rotator cuff tear, and provides a framework for physicians to better prescribe long-term treatment strategies for patients.