Denervation alters mRNA levels of repair-associated genes in a rabbit medial collateral ligament injury model.
Previous experiments revealed that denervation impairs healing of the MCL. This suggested the hypothesis that denervation would decrease repair-associated mRNA levels in the injured MCL when compared with normally innervated injured MCL. Adult, skeletally mature female rabbits were assigned to one of four groups: unoperated control, femoral nerve transection alone (denervated controls), MCL partial tear or denervated MCL partial tear. At three days, two weeks, six weeks or sixteen weeks post-surgery, cohorts of 6 rabbits from each experimental group were killed. Ligaments were harvested, RNA extracted and RT-PCR was performed using rabbitspecific primers. In the denervated injury group, mRNA levels for the angiogenesis-associated gene MMP-13, matrix components Collagen I and III, growth factor TGF-beta and angiogenesis inhibitors TIMP-3, and TSP-1 had all increased by two-weeks post-injury, in comparison to the non-denervated injury group (p < or = 0.01). An increased level of TSP-1 mRNA was also detected in the denervated injured group at sixteen weeks post injury (p < or = 0.01). Contrary to the initial hypothesis, denervation led to increased mRNA levels for many relevant molecules during the early stages of MCL healing. Thus, inappropriate timing of over-expression of some molecules may potentially contribute to the decreased quality of the scar tissue, particularly molecules such as TSP-1. Neuronal derived factors strongly influence the in vivo metabolic activity of ligament and scar fibroblasts in the initial phases of healing.
Beye
Jasmine A
JA
McCaig Centre for Joint Injury and Arthritis Research, Department of Surgery, University of Calgary, Alberta, Canada T2N 4N1.
Hart
David A
DA
Bray
Robert C
RC
Seerattan
Ruth A
RA
McDougall
Jason J
JJ
Leonard
Catherine A
CA
Reno
Carol R
CR
Salo
Paul T
PT
D000818:Animals; D002921:Cicatrix / Q000235:genetics / Q000378:metabolism; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003714:Denervation; D005260:Female; D005267:Femoral Nerve / Q000601:surgery; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D007718:Knee Injuries / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D017888:Medial Collateral Ligament, Knee / Q000293:injuries / Q000294:innervation* / Q000378:metabolism*; D023421:Models, Animal; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D012333:RNA, Messenger; D019700:Thrombospondin 1; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D020932:Nerve Growth Factor; D020782:Matrix Metalloproteinases