title: High strain mechanical loading rapidly induces tendon apoptosis: an ex vivo rat tibialis anterior model.
abstract: BACKGROUND
  The role of apoptosis, or programmed cell death, has only recently been explored in tendon.
  
  
  OBJECTIVE
  To investigate the development of apoptosis after high strain loading of rat tendon.
  
  
  METHODS
  The right tibialis anterior tendons of three rats were prepared for mechanical loading, and left tendons were prepared identically as non-loaded controls. Tendon was loaded with 20% strain for six hours using a 1 Hz longitudinal sine wave signal. The following were used to assess apoptosis: (a) a monoclonal mouse antibody (F7-26) to label single stranded DNA breaks; (b) a rabbit polyclonal antibody that specifically recognises the cleaved form of caspase-3.
  
  
  RESULTS
  Light microscopy confirmed that the high strain protocol induced a stretch overload injury. Control tendons showed little or no staining with the F7-26 antibody, but the loaded tendons displayed numerous apoptotic cells. The percentage of apoptotic cells (20%) in the loaded tendon was significantly greater than in the control tendon (1%) (p = 0.000). The labelled cells colocalised with abnormal nuclear morphology, including nuclear fragmentation. The staining against cleaved caspase-3 was positive in loaded tendons only, and localised both to nucleus and cytoplasm.
  
  
  CONCLUSIONS
  This experiment extends knowledge of human tendon apoptosis by showing that apoptosis can occur in response to short term, high strain mechanical loading. This is the first report of mechanical loading of intact tendon causing excessive apoptosis.
authors.affiliation: Department of Family Practice & School of Human Kinetics, University of British Columbia, Vancouver, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Scott
authors.forename: K M
authors.initials: KM
authors.lastname: Khan
authors.forename: J
authors.initials: J
authors.lastname: Heer
authors.forename: J L
authors.initials: JL
authors.lastname: Cook
authors.forename: O
authors.initials: O
authors.lastname: Lian
authors.forename: V
authors.initials: V
authors.lastname: Duronio
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D012090:Cumulative Trauma Disorders / Q000473:pathology; D053938:DNA Fragmentation / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008853:Microscopy / Q000379:methods; D051381:Rats; D020318:Rats, Long-Evans; D013314:Stress, Mechanical; D013708:Tendon Injuries / Q000473:pathology*