title: Stochastic amplitude-modulated stretching of rabbit flexor digitorum profundus tendons reduces stiffness compared to cyclic loading but does not affect tenocyte metabolism.
abstract: BACKGROUND
  It has been demonstrated that frequency modulation of loading influences cellular response and metabolism in 3D tissues such as cartilage, bone and intervertebral disc. However, the mechano-sensitivity of cells in linear tissues such as tendons or ligaments might be more sensitive to changes in strain amplitude than frequency. Here, we hypothesized that tenocytes in situ are mechano-responsive to random amplitude modulation of strain.
  
  
  METHODS
  We compared stochastic amplitude-modulated versus sinusoidal cyclic stretching. Rabbit tendon were kept in tissue-culture medium for twelve days and were loaded for 1h/day for six of the total twelve culture days. The tendons were randomly subjected to one of three different loading regimes: i) stochastic (2 - 7% random strain amplitudes), ii) cyclic_RMS (2-4.42% strain) and iii) cyclic_high (2 - 7% strain), all at 1 Hz and for 3,600 cycles, and one unloaded control.
  
  
  RESULTS
  At the end of the culture period, the stiffness of the "stochastic" group was significantly lower than that of the cyclic_RMS and cyclic_high groups (both, p < 0.0001). Gene expression of eleven anabolic, catabolic and inflammatory genes revealed no significant differences between the loading groups.
  
  
  CONCLUSIONS
  We conclude that, despite an equivalent metabolic response, stochastically stretched tendons suffer most likely from increased mechanical microdamage, relative to cyclically loaded ones, which is relevant for tendon regeneration therapies in clinical practice.
authors.affiliation: Institute for Surgical Technology and Biomechanics, University of Bern, Switzerland.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Steiner
authors.forename: Alexander
authors.initials: A
authors.lastname: Bürki
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ferguson
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gantenbein-Ritter
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D049109:Cell Proliferation; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004548:Elasticity; D005260:Female; D005786:Gene Expression Regulation; D006025:Glycosaminoglycans / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D011817:Rabbits; D013269:Stochastic Processes; D013314:Stress, Mechanical; D013708:Tendon Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013710:Tendons / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D016474:Weight-Bearing
chemical_list: D006025:Glycosaminoglycans; D004247:DNA