Sarah Ilkhanipour Rooney

Disruption of the anterior-posterior rotator cuff force balance alters joint function and leads to joint damage in a rat model.

The rotator cuff assists in shoulder movement and provides dynamic stability to the glenohumeral joint. Specifically, the anterior–posterior (AP) force balance, provided by the subscapularis anteriorly and the infraspinatus and teres minor posteriorly, is critical for joint stability and concentric rotation of the humeral head on the glenoid. However, limited understanding exists of the consequences associated with disruption of the AP force balance (due to tears of both the supraspinatus and infraspinatus tendons) on joint function and joint damage. We investigated the effect of disrupting the APforce balance on joint function and joint damage in an overuse rat model. Twenty‐eight rats underwent 4 weeks of overuse to produce a tendinopathic condition and were then randomized into two surgical groups: Detachment of the supraspinatus only or detachment of the supraspinatus and infraspinatus tendons. Rats were then gradually returned to their overuse protocol. Quantitative ambulatory measures including medial/lateral, propulsion, braking, and vertical forces were significantly different between groups. Additionally, cartilage and adjacent tendon properties were significantly altered. These results identify joint imbalance as a mechanical mechanism for joint damage and demonstrate the importance of preserving rotator cuff balance when treating active cuff tear patients.

Ibuprofen Differentially Affects Supraspinatus Muscle and Tendon Adaptations to Exercise in a Rat Model

Background: Previous studies have shown that ibuprofen is detrimental to tissue healing after acute injury; however, the effects of ibuprofen when combined with noninjurious exercise are debated. Hypothesis: Administration of ibuprofen to rats undergoing a noninjurious treadmill exercise protocol will abolish the beneficial adaptations found with exercise but will have no effect on sedentary muscle and tendon properties. Study Design: Controlled laboratory study. Methods: A total of 167 male Sprague-Dawley rats were divided into exercise or cage activity (sedentary) groups and acute (a single bout of exercise followed by 24 hours of rest) and chronic (2 or 8 weeks of repeated exercise) response times. Half of the rats were administered ibuprofen to investigate the effects of this drug over time when combined with different activity levels (exercise and sedentary). Supraspinatus tendons were used for mechanical testing and histologic assessment (organization, cell shape, cellularity), and supraspinatus muscles were used for morphologic (fiber cross-sectional area, centrally nucleated fibers) and fiber type analysis. Results: Chronic intake of ibuprofen did not impair supraspinatus tendon organization or mechanical adaptations (stiffness, modulus, maximum load, maximum stress, dynamic modulus, or viscoelastic properties) to exercise. Tendon mechanical properties were not diminished and in some instances increased with ibuprofen. In contrast, total supraspinatus muscle fiber cross-sectional area decreased with ibuprofen at chronic response times, and some fiber type–specific changes were detected. Conclusion: Chronic administration of ibuprofen does not impair supraspinatus tendon mechanical properties in a rat model of exercise but does decrease supraspinatus muscle fiber cross-sectional area. This fundamental study adds to the growing literature on the effects of ibuprofen on musculoskeletal tissues and provides a solid foundation on which future work can build. Clinical Relevance: The study findings suggest that ibuprofen does not detrimentally affect regulation of supraspinatus tendon adaptations to exercise but does decrease muscle growth. Individuals should be advised on the risk of decreased muscle hypertrophy when consuming ibuprofen.

Genetic Response of Rat Supraspinatus Tendon and Muscle to Exercise.

Inflammation is a complex, biologic event that aims to protect and repair tissue. Previous studies suggest that inflammation is critical to induce a healing response following acute injury; however, whether similar inflammatory responses occur as a result of beneficial, non-injurious loading is unknown. The objective of this study was to screen for alterations in a subset of inflammatory and extracellular matrix genes to identify the responses of rat supraspinatus tendon and muscle to a known, non-injurious loading condition. We sought to define how a subset of genes representative of specific inflammation and matrix turnover pathways is altered in supraspinatus tendon and muscle 1) acutely following a single loading bout and 2) chronically following repeated loading bouts. In this study, Sprague-Dawley rats in the acute group ran a single bout of non-injurious exercise on a flat treadmill (10 m/min, 1 hour) and were sacrificed 12 or 24 hours after. Rats in the chronic group ran 5 days/wk for 1 or 8 weeks. A control group maintained normal cage activity. Supraspinatus muscle and tendon were harvested for RNA extractions, and a custom Panomics QuantiGene 2.0 multiplex assay was used to detect 48 target and 3 housekeeping genes. Muscle/tendon and acute/chronic groups had distinct gene expression. Components of the arachidonic acid cascade and matrix metalloproteinases and their inhibitors were altered with acute and chronic exercise. Collagen expression increased. Using a previously validated model of non-injurious exercise, we have shown that supraspinatus tendon and muscle respond to acute and chronic exercise by regulating inflammatory- and matrix turnover-related genes, suggesting that these pathways are involved in the beneficial adaptations to exercise.

Rat Supraspinatus Tendon Responds Acutely and Chronically to Exercise

The objective of this study was to identify acute responses and chronic adaptations of supraspinatus tendon to noninjurious exercise. We hypothesized that chronic exercise (EX) increases tendon mechanical properties, and a single exercise bout increases matrix metalloproteinase (MMP) activity acutely. Rats were divided into acute or chronic EX or cage activity groups. Animals in acute EX groups were euthanized, 3, 12, 24, 48, or 72 h upon completion of a single bout of exercise (10 m/min, 1 h) on a flat treadmill. Animals in chronic EX groups walked on a flat treadmill for 3 days or 1, 2, or 8 wk. Tendon histology, MMP activity, and mechanics were measured. A single bout of exercise trended toward reducing tendon mechanical properties, but 2 or 8 wk of chronic EX increased tendon mechanics. Cell density was not affected. Cells became rounder with chronic EX. All tendons were highly organized. MMP activity decreased after a single bout of exercise and returned to baseline by 72 h. MMP activity decreased after 8 wk of chronic EX. Decreased MMP activity may indicate an anabolic instead of catabolic response in contrast to injury. Results suggest that mild, acute decreases in MMP activity and tendon mechanics following a single exercise bout lead to enhanced tendon mechanical adaptations with repeated exercise bouts. This study defines acute and chronic changes of MMP activity, mechanical properties, and histology of the rat supraspinatus tendon in response to beneficial exercise and proposes a mechanism by which acute responses translate to chronic adaptations.NEW & NOTEWORTHY The line between beneficial exercise and overuse has not been elucidated. This study defines the acute and chronic temporal response to exercise of supraspinatus tendon in an in vivo model. We found that decreased matrix metalloproteinase activity and tendon mechanics after a single bout of exercise are followed by beneficial chronic adaptations of the tendon with repeated bouts. How the acute responses to exercise lead to chronic adaptations may distinguish beneficial exercise from overuse.

Doxycycline improves cage activity, but not exercised, supraspinatus tendon and muscle in a rat model

The objective of this study was to investigate the effects of doxycycline, a broad-spectrum MMP inhibitor, on cage activity and exercised supraspinatus tendon and muscle using a Sprague-Dawley rat model of non-injurious exercise. Because exercise may alter muscle and tendon MMP activity and matrix turnover, we hypothesized that doxycycline would abolish the beneficial adaptations found with exercise but have no effect on cage activity muscle and tendon properties. Rats were divided into acute or chronic exercise (EX) or cage activity (CA) groups, and half of the rats received doxycycline orally. Animals in acute EX groups were euthanized 24 h after a single bout of exercise (10 m/min, 1 h) on a flat treadmill. Animals in chronic EX groups walked on a flat treadmill and were euthanized at 2 or 8 week time points. Assays included supraspinatus tendon mechanics and histology and muscle fiber morphologic and type analysis. Doxycycline improved tendon mechanical properties and collagen organization in chronic cage activity groups, which was not consistently evident in exercised groups. Combined with exercise, doxycycline decreased average muscle fiber cross-sectional area. Results of this study suggest that administration of doxycycline at pharmaceutical doses induces beneficial supraspinatus tendon adaptations without negatively affecting the muscle in cage activity animals, supporting the use of doxycycline to combat degenerative processes associated with underuse; however, when combined with exercise, doxycycline does not consistently produce the same beneficial adaptations in rat supraspinatus tendons and reduces muscle fiber cross-sectional area, suggesting that doxycycline is not advantageous when combined with activity.

Erratum to: Biceps Detachment Decreases Joint Damage in a Rotator Cuff Tear Rat Model

The online version of the original article can be found under doi:10.1007/s11999-013-3422-8.