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

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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.

Section snippets

Materials and methods

Institutional ethics committee approval was granted by Sir Charles Gairdner Hospital Human Ethic committee for this study that analyzed extensor carpi radialis brevis (ECRB) tendon samples obtained during surgical débridement and lateral epicondylar release, as treatment for refractory and severe lateral epicondylitis.

General histology

On H&E staining, the degenerated ECRB samples revealed a highly variable collagen structure and cellular morphology. In grade I areas, collagen fibers were continuously packed in a parallel pattern with slight splitting between bundles, and nearly all tendon cells were spindle shaped and aligned along the fiber orientation (Figure 1, B). In grade II areas, splitting and fragmentation of fiber bundles were common, with intense small blood vessel genesis and cellular proliferation. A large

Discussion

In this study, we demonstrated elevated apoptotic and autophagic cell death rates in chronic lateral epicondylitis samples. The mean apoptotic rate of degenerated ERCB tendon débrided at surgery was 28.7% ± 5.6%, which is much higher than the apoptotic rate of 13% found in normal rotator cuff tendon30 and the 3% to 10% rate found in normal adult articular cartilage.1 Our results are similar to those reported in previous studies that also used the TUNEL assay to detect apoptosis. Yuan et al30

Disclaimer

All authors, their immediate family, and any research foundation with which they are affiliated did not receive any financial payments or other benefits from any commercial entity related to the subject of this article. No external funding was received in assisting this study.

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