Is apoptosis the cause of noninsertional achilles tendinopathy?
BACKGROUND
The pathogenesis of chronic tendinopathy is unclear but it does not appear to be an inflammatory process. Apoptosis may lead to degenerate tissue through a nitric oxide-mediated pathway. Increased levels of nitric oxide have been demonstrated in Achilles tendinopathy.


OBJECTIVE
Nitric oxide-mediated apoptosis is an important mechanism in the development of Achilles tendinopathy.


METHODS
Controlled laboratory study.


METHODS
Samples were obtained from the Achilles tendons of 14 patients with noninsertional Achilles tendinopathy. Control samples were taken from macroscopically normal tendon correlating with areas of normal tissue on magnetic resonance imaging. Immunohistochemical techniques identified the expression of inducible and endothelial nitric oxide synthase as markers of nitric oxide production. Apoptotic cells were identified using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and the demonstration of caspase-3 activation.


RESULTS
Significant differences were found between the diseased tendon and the controls for all parameters. The mean caspase-3 cell count for diseased tendon was 51.9 versus 28.3 for the controls (P < .001). The mean TUNEL cell count for diseased tendon was 24.1 compared with 14.8 (P < .001). Inducible nitric oxide synthase (iNOS) densitometry revealed a mean of 26.1 for the diseased tissue versus 15.0 for the controls (P < .001) and the values for endothelial nitric oxide synthase (eNOS) were 48.3 and 23.7, respectively (P = .015).


CONCLUSIONS
Apoptosis may play a role in the development of noninsertional Achilles tendinopathy and appears to be related to the presence of raised eNOS and iNOS levels.


CONCLUSIONS
A clearer understanding of the tendinopathic process may lead to new treatment strategies aimed at modulating apoptosis.
Pearce
Christopher J
CJ
Department of Trauma and Orthopaedic Surgery, Basingstoke and North Hampshire Hospitals, NHS Foundation Trust, Basingstoke, United Kingdom. chris.pearce@doctors.org.uk
Ismail
Muhammad
M
Calder
James D
JD
D000125:Achilles Tendon / Q000473:pathology*; D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D052256:Tendinopathy / Q000209:etiology / Q000378:metabolism*; D055815:Young Adult
D009569:Nitric Oxide; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III