In chronic lateral epicondylitis, apoptosis and autophagic cell death occur in the extensor carpi radialis brevis tendon

Hypothesis: Despite its common occurrence, lateral epicondylitis is poorly understood from a cellular and molecular perspective. We hypothesize that apoptosis and autophagic cell death are involved in the development of chronic lateral epicondylitis. Materials and methods: In 10 patients undergoing surgery for chronic recalcitrant lateral epicondylitis, tendon samples were taken from the extensor carpi radialis brevis (ECRB) tendon and were processed for hematoxylin and eosin, terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate nick-end labeling (TUNEL) assay, and immunostaining. Extracellular matrix structure was graded I to III according to collagen fiber structure and arrangement. Apoptotic rate, autophagic cell death rate, cell density, and type I collagen content were measured and compared between areas with different collagen grade. Results: Apoptotic and autophagic cell death occur in the ECRB tendon and varied with the grade of collagen structure. In grade I matrix with relatively less disrupted collagen structure, the apoptosis rate was 23.2% +/- 4.8% and the autophagy cell death rate was 7.6% +/- 2.2%. In grade II matrix with more advanced breakdown of collagen structure, the apoptosis rate increased to 34.4% +/- 4% (P < .05) and the autophagic cell death rate to 13.7% +/- 3% (P < .05). Discussion: This study demonstrated that apoptosis and autophagic cell death occur in the ECRB tendon in chronic lateral epicondylitis. The markedly elevated apoptotic rate and autophagic cell death rate in the grade II matrix may be responsible for the decrease in cellularity and further deterioration of collagen quality seen in end-stage grade III matrix, and this eventually compromised the tendon's ability to maintain its integrity and resulted in tendon tear. Conclusion: Both apoptosis and autophagic cell death play an important role in the development of tendon degeneration in chronic lateral epicondylitis. Level of evidence: Basic science study. 2010 Journal of Shoulder and Elbow Surgery Board of Trustees.