PMID- 19741110
OWN - NLM
STAT- MEDLINE
DCOM- 20100323
LR  - 20131121
IS  - 1552-3365 (Electronic)
IS  - 0363-5465 (Linking)
VI  - 37
IP  - 12
DP  - 2009 Dec
TI  - Is apoptosis the cause of noninsertional achilles tendinopathy?
PG  - 2440-4
LID - 10.1177/0363546509340264 [doi]
AB  - 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. HYPOTHESIS: Nitric oxide-mediated 
      apoptosis is an important mechanism in the development of Achilles tendinopathy. 
      STUDY DESIGN: 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). CONCLUSION: 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. CLINICAL RELEVANCE: A 
      clearer understanding of the tendinopathic process may lead to new treatment 
      strategies aimed at modulating apoptosis.
FAU - Pearce, Christopher J
AU  - Pearce CJ
AD  - Department of Trauma and Orthopaedic Surgery, Basingstoke and North Hampshire 
      Hospitals, NHS Foundation Trust, Basingstoke, United Kingdom. 
      chris.pearce@doctors.org.uk
FAU - Ismail, Muhammad
AU  - Ismail M
FAU - Calder, James D
AU  - Calder JD
LA  - eng
PT  - Journal Article
DEP - 20090909
PL  - United States
TA  - Am J Sports Med
JT  - The American journal of sports medicine
JID - 7609541
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (NOS2 protein, human)
RN  - EC 1.14.13.39 (NOS3 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
SB  - IM
MH  - Achilles Tendon/*pathology
MH  - Adult
MH  - Apoptosis/*physiology
MH  - Humans
MH  - Middle Aged
MH  - Nitric Oxide/biosynthesis/*physiology
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Tendinopathy/etiology/*metabolism
MH  - Young Adult
EDAT- 2009/09/11 06:00
MHDA- 2010/03/24 06:00
CRDT- 2009/09/11 06:00
PHST- 2009/09/11 06:00 [entrez]
PHST- 2009/09/11 06:00 [pubmed]
PHST- 2010/03/24 06:00 [medline]
AID - 0363546509340264 [pii]
AID - 10.1177/0363546509340264 [doi]
PST - ppublish
SO  - Am J Sports Med. 2009 Dec;37(12):2440-4. doi: 10.1177/0363546509340264. Epub 2009 
      Sep 9.