The subacromial bursa is a key regulator of the rotator cuff and a new therapeutic target for improving repair

Marshall, B. P.; Ferrer, X. E.; Kunes, J. A.; Innis, A. C.; Luzzi, A. J.; Forrester, L. A.; Burt, K. G.; Lee, A. J.; Song, L.; Hung, C. T.; Levine, W. N.; Kovacevic, D.; Thomopoulos, S.

doi:10.1101/2023.07.01.547347

bioRxiv · 10.1101/2023.07.01.547347

The subacromial bursa is a key regulator of the rotator cuff and a new therapeutic target for improving repair

Marshall, B. P.·Ferrer, X. E.·Kunes, J. A.·Innis, A. C.·Luzzi, A. J.·Forrester, L. A.·Burt, K. G.·Lee, A. J.·Song, L.·Hung, C. T.·Levine, W. N.·Kovacevic, D.·Thomopoulos, S.

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Abstract

Rotator cuff injuries result in over 500,000 surgeries performed annually, an alarmingly high number of which fail. These procedures typically involve repair of the injured tendon and removal of the subacromial bursa. However, recent identification of a resident population of mesenchymal stem cells and inflammatory responsiveness of the bursa to tendinopathy indicate an unexplored biological role of the bursa in the context of rotator cuff disease. Therefore, we aimed to understand the clinical relevance of bursa-tendon crosstalk, characterize the biologic role of the bursa within the shoulder, and test the therapeutic potential for targeting the bursa. Proteomic profiling of patient bursa and tendon samples demonstrated that the bursa is activated by tendon injury. Using a rat to model rotator cuff injury and repair, tenotomy-activated bursa protected the intact tendon adjacent to the injured tendon and maintained the morphology of the underlying bone. The bursa also promoted an early inflammatory response in the injured tendon, initiating key players in wound healing. In vivo results were supported by targeted organ culture studies of the bursa. To examine the potential to therapeutically target the bursa, dexamethasone was delivered to the bursa, prompting a shift in cellular signaling towards resolution of inflammation in the healing tendon. In conclusion, contrary to current clinical practice, the bursa should be retained to the greatest extent possible and provides a new therapeutically target for improving tendon healing outcomes. One Sentence SummaryThe subacromial bursa is activated by rotator cuff injury and regulates the paracrine environment of the shoulder to maintain the properties of the underlying tendon and bone.

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Marshall, B. P., Ferrer, X. E., Kunes, J. A., Innis, A. C., Luzzi, A. J., Forrester, L. A., Burt, K. G., Lee, A. J., Song, L., Hung, C. T., Levine, W. N., Kovacevic, D., Thomopoulos, S.. 2023-07-02. The subacromial bursa is a key regulator of the rotator cuff and a new therapeutic target for improving repair. https://doi.org/10.1101/2023.07.01.547347

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