Ex vivo static tensile loading inhibits MMP-1 expression in rat tail tendon cells through a cytoskeletally based mechanotransduction mechanism.
To determine the effect of various degrees of ex vivo static tensile loading on the expression of collagenase (MMP-1) in tendon cells, rat tail tendons were statically loaded in tension at 0.16, 0.77, 1.38 or 2.6 MPa for 24 h. Northern blot analysis was used to assay for mRNA expression of MMP-1 in freshly harvested, 24 h load deprived, and 24 h statically loaded tendons. Western blot analysis was used to assay for pro-MMP-1 and MMP-1 protein expression in fresh and 24 h load deprived tendons. Freshly harvested rat tail tendons demonstrated no evidence of MMP-1 mRNA expression and no evidence of the pro-MMP-1 or MMP-1 protein. Ex vivo load deprivation for 24 h resulted in a marked increase in the mRNA expression of MMP-1 which coincided with a marked increase of both pro-MMP-1 and MMP-1 protein expression. When tendons were subjected to ex vivo static tensile loading during the 24 h culture period, a significant inhibition of this upregulation of MMP-1 mRNA expression was found with increasing load (p<0.05). A strong (r2=0.78) and significant (p<0.001) inverse correlation existed between the level of static tensile load and the expression of MMP-1. Disruption of the actin cytoskeleton with cytochalasin D abolished the inhibitory effect of ex vivo static tensile loading on MMP-1 expression. The results of this study suggest that up-regulation of MMP-1 expression in tendon cells ex vivo can be inhibited by static tensile loading, presumably through a cytoskeletally based mechanotransduction pathway.
Arnoczky
Steven P
SP
Laboratory for Comparative Orthopaedic Research, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA. arnoczky@cvm.msu.edu
Tian
Tao
T
Lavagnino
Michael
M
Gardner
Keri
K
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D015870:Gene Expression; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013623:Tail; D013710:Tendons / Q000166:cytology / Q000378:metabolism*; D013718:Tensile Strength; D016474:Weight-Bearing / Q000502:physiology*
D012333:RNA, Messenger; D015638:Cytochalasin D; D020781:Matrix Metalloproteinase 1