Apoptosis Occurs Throughout the Diseased Rotator Cuff

Background: Even though apoptosis is known to be closely associated with rotator cuff tears, the differences in apoptosis according to the location within the torn supraspinatus tendon are still unknown. Purpose: To elucidate where apoptosis begins within the supraspinatus tendon. Study Design: Controlled laboratory study. Methods: Tendon tissues were collected from 14 patients undergoing arthroscopic rotator cuff repair surgery and 7 patients undergoing surgery for proximal humeral fracture who served as controls. In the patients with rotator cuff tears, the samples were harvested at 3 sites: the most lateral torn margin, 1 cm medial from the torn margin, and at the posterior torn corner. Caspase 3/7, 8, and 9 and cytochrome c activities were measured to determine the intracellular apoptosis pathway. Apoptotic cells were determined by in situ TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) staining, and immunohistochemistry was performed. Results: The apoptotic activities of tendons from the experimental subjects were significantly higher than those of the controls. There were, however, no significant differences between the 3 sample sites. Immunohistochemistry also revealed strong expression of increased caspase 3/7, 8, and 9 and cytochrome c but no significant difference between them. Conclusion: This study shows that the intracellular apoptotic pathway is not only through the cell membrane receptor but also via intracellular mitochondria cascade. Clinical Relevance: Because apoptosis occurs regardless of the location within the rotator cuff, debridement of the torn margin to obtain a healthy tendon may not be needed. Further study should focus on not only the technique of tying the torn tendon back to the bone but also biological augmentation to reverse or prevent further apoptosis within rotator cuff tendon.