Abstract
Joint instability was induced by posterior cruciate ligament (PCL) transection. This resulted in significant changes in medial collateral ligament (MCL) gene expression as early as three days after injury that persisted as long as 6 weeks. We noted substantial changes in expression of matrix-metalloproteinases (MMPs) −1, −3 and -13, with reciprocal effects on their specific inhibitors TIMP-1 and −3. Sustained changes in expression of these angiogenesis-associated matrix-degrading enzymes likely account for the observed degradation of the mechanical properties of secondary stabilizers in chronically unstable joints.
To determine changes in gene-expression induced by traumatic instability.
Instability activates aberrant expression of angiogenesis-associated matrix metalloproteinases.
PCL transection induces a significant increase in the expression of MMP-3 and decrease in its specific inhibitor TIMP-3 with opposite effects on MMP-1 and TIMP-1 as early as three days after injury.
Understanding the changes in gene expression induced by instability may lead to specific treatments that could prevent the “collateral damage” to secondary stabilizing structures.
Under anaesthesia, four cohorts of six adult rabbits underwent surgical transection of the PCL. Three days, and two, six and sixteen weeks later, the MCL was harvested and the relative expression of TGF-β, MMP-1, -3, and −13, and their tissues inhibitors, and urokinase-type plasminogen activator (uPA) was measured using semi-quantitative RT-PCR.
Previous work revealed increased in blood flow by two weeks and increased vascular volume by six weeks in the MCL of PCL-deficient joints. These changes are preceded by substantial changes in expression of mRNA for matrix degradation enzymes involved in the early stages of angiogenesis. This aberrant expression of matrix metalloproteinases likely accounts for the progressive degradation of the mechanical properties of secondary stabilizing structures seen in chronic instability.
Funding: This work was supported by funding from the CIHR and the Alberta Heritage Foundation for Medical Research.
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Correspondence should be addressed to Cynthia Vezina, Communications Manager, COA, 4150-360 Ste. Catherine St. West, Westmount, QC H3Z 2Y5, Canada
