title: Changes in mechanical loading lead to tendonspecific alterations in MMP and TIMP expression: influence of stress deprivation and intermittent cyclic hydrostatic compression on rat supraspinatus and Achilles tendons.
abstract: BACKGROUND
  Tendinopathy commonly occurs in tendons with large in vivo loading demands like the Achilles tendon (AT) and supraspinatus tendon (SST). In addition to differences in their local anatomic environment, these tendons are designed for different loading requirements because of the muscles to which they attach, with the AT experiencing higher loads than the SST. One possible factor in the progression of tendinopathy is the interplay between mechanical loading and the regulation of enzymes that degrade the extracellular matrix (matrix metalloproteinases (MMPs)) and their inhibitors (tissue inhibitor of metalloprotienases (TIMPs)). Thus, overuse injuries may have different biological consequences in tendons designed for different in vivo loading demands.
  
  
  OBJECTIVE
  In this study, the tendon-specific regulation of MMP-13, MMP-3 and TIMP-2 expression in rat AT and SST exposed to two different mechanical environments was investigated.
  
  
  METHODS
  Rat AT and SST were exposed to stress deprivation (ie, detached from attachments) and intermittent cyclic hydrostatic compression (with attachments intact). Levels of MMP-13, MMP-3 and TIMP-2 mRNA were evaluated in time-zero control, attached, stressdeprived and "compressed" tendons.
  
  
  RESULTS
  Stress deprivation led to elevated expression of MMP-13, MMP-3 and TIMP-2 in both tendons, although the magnitude of the increase was greater for the SST than the AT. Intermittent cyclic hydrostatic compression of attached tendons increased expression of MMP-13 in the SST, but not the AT.
  
  
  CONCLUSIONS
  The results of this study suggest that stress deprivation may be one contributor to the progression of tendinopathy in AT and SST, where the tendon designed for the lower in vivo loading demand (SST) was the most affected by a change in mechanical loading. The unique upregulation of MMP-13 with hydrostatic compression supports the impingement injury theory for rotator cuff tears.
authors.affiliation: Department of Surgery, University of Calgary, 451A Heritage Medical Research Building, 3330 Hospital Dr NW, Calgary, Alberta T2N4N1, Canada. gail.thornton@ucalgary.ca
authors.forename: G M
authors.initials: GM
authors.lastname: Thornton
authors.forename: X
authors.initials: X
authors.lastname: Shao
authors.forename: M
authors.initials: M
authors.lastname: Chung
authors.forename: P
authors.initials: P
authors.lastname: Sciore
authors.forename: R S
authors.initials: RS
authors.lastname: Boorman
authors.forename: D A
authors.initials: DA
authors.lastname: Hart
authors.forename: I K Y
authors.initials: IK
authors.lastname: Lo
mesh_terms: D000125:Achilles Tendon / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D017403:In Situ Hybridization; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017006:Rotator Cuff / Q000378:metabolism*; D013314:Stress, Mechanical; D052256:Tendinopathy / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D019716:Tissue Inhibitor of Metalloproteinase-2; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3