OR13: ADAMTS-5 DEFICIENCY DECREASES THE MATERIAL PROPERTIES OF STRESS DEPRIVED MOUSE TAIL TENDONS

Abstract

The morbidity associated with tendinopathy is a costly burden on our health system. Recent investigations in our laboratory have shown that alterations in mechanical stress cause significant changes in tendon expression of key matrix molecules and proteolytic enzymes including the aggrecanase molecules, (e.g. ADAMTS-5). Here, we investigate the biomechanical consequences of such altered tensile stress in tail tendons from mice with and without deletion of the ADAMTS-5 gene. Tail tendons from 12 week old C57BL6 wild type and ADAMTS-5 knock-out mice were immediately snap frozen (ex vivo), or cultured stress deprived for 120 hours in DMEM/10% FCS (eight tendons per group). Material properties including maximum stress, strain and elastic modulus were determined for each tendon in uniaxial tension to failure at a constant strain rate of 1.0 mm/second (10% strain/second) on an Instron 8874 servo-hydraulic testing apparatus. Significant differences between groups were determined with Kruskal-Wallis one-way analysis of variance, followed by Mann-Whitney U test with Benjamini-Hochberg post-hoc corrections for multiple comparisons. Stress deprivation for 120 hours led to a significant increase in maximum stress for both the wild type (~150% increase, p = 0.0008) and ADAMTS-5 deficient (~100%, p = 0.0033) mice when compared to ex vivo tendon. Stress deprivation led to a 100% increase in elastic modulus compared to ex vivo for the wild type tendons (p = 0.0033) but failed to increase this parameter in the ADAMTS-5 deficient mice. When the effect of stress deprivation of the ADAMTS-5 deficient mice was directly compared to the wild type stress deprived tendons, a 35% decrease in elastic modulus was found (p = 0.021). We have shown for the first time that deletion of an aggrecanase molecule significantly decreases the material properties of tendon. Alterations in the expression of the aggrecanase molecules may play a role in the development and progression of tendinopathy through their ability to modulate the metabolism of aggrecan [1]. Previous research in our laboratory has shown that aggrecanase expression is markedly up-regulated by stress deprivation. This finding in combination with the results of the present study suggest that the aggrecanase molecules may provide a future therapeutic target for the treatment tendinopathy.