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Cathepsins in Rotator Cuff Tendinopathy: Identification in Human Chronic Tears and Temporal Induction in a Rat Model

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While overuse of the supraspinatus tendon is a leading factor in rotator cuff injury, the underlying biochemical changes have not been fully elucidated. In this study, torn human rotator cuff (supraspinatus) tendon tissue was analyzed for the presence of active cathepsin proteases with multiplex cysteine cathepsin zymography. In addition, an overuse injury to supraspinatus tendons was induced through downhill running in an established rat model. Histological analysis demonstrated that structural damage occurred by 8 weeks of overuse compared to control rats in the region of tendon insertion into bone. In both 4- and 8-week overuse groups, via zymography, there was approximately a 180% increase in cathepsin L activity at the insertion region compared to the controls, while no difference was found in the midsubstance area. Additionally, an over 400% increase in cathepsin K activity was observed for the insertion region of the 4-week overused tendons. More cathepsin K and L immunostaining was observed at the insertion region of the overuse groups compared to controls. These results provide important information on a yet unexplored mechanism for tendon degeneration that may operate alone or in conjunction with other proteases to contribute to chronic tendinopathy.

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The authors thank Jennifer Lei for assistance in animal studies, Meredith Fay and Ang (Kevin) Li for help in tissue processing, and Bernard Kippelen’s laboratory at Georgia Tech for use of the circular polarized microscope. This study was supported by a National Football League Charities Medical Grant, a Regenerative Engineering and Medicine Seed Grant (REM) from Georgia Tech and Emory University through the Atlanta Clinical & Translational Science Institute (Advancing Translational Sciences of the National Institutes of Health, UL1TR000454) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R01AR063692. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Correspondence to Johnna S. Temenoff.

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Associate Editor Michael S. Detamore oversaw the review of this article.

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Seto, S.P., Parks, A.N., Qiu, Y. et al. Cathepsins in Rotator Cuff Tendinopathy: Identification in Human Chronic Tears and Temporal Induction in a Rat Model. Ann Biomed Eng 43, 2036–2046 (2015).

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