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Denervation alters mRNA levels of repair‐associated genes in a rabbit medial collateral ligament injury model
Author(s) -
Beye Jasmine A.,
Hart David A.,
Bray Robert C.,
Seerattan Ruth A.,
McDougall Jason J.,
Leonard Catherine A.,
Reno Carol R.,
Salo Paul T.
Publication year - 2006
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.20219
Subject(s) - denervation , angiogenesis , in vivo , medial collateral ligament , messenger rna , medicine , ligament , andrology , pathology , endocrinology , biology , anatomy , gene , biochemistry , microbiology and biotechnology
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‐β 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 ≤ 0.01). An increased level of TSP‐1 mRNA was also detected in the denervated injured group at sixteen weeks post injury ( p ≤ 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. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res