Abstract
Tendinosis is a common problem causing wide spread morbidity ranging from mild symptoms of pain and limited mobility to catastrophic end stage rupture. The structural and mechanical properties of the rat Achilles tendon were investigated as groundwork for the development of a rat Achilles tendinosis model. This model will generate tendons afflicted with tendinosis that bear histological features identical to those observed in human tendinosis. Tissues afflicted with tendinosis derived from this model will be used in future studies to gain a better understanding of the biology of tendinosis and to evaluate various therapeutic intervention strategies.
The pathology underlying tendinosis is a continuum, with mild symptoms progressing toward catastrophic rupture; still, the corresponding biochemical and biomechanical progression is poorly understood.
We have developed a rat model for Achilles tendinosis, aiming to: (i) define for the first time the structural/mechanical features of the normal tendon and (ii) examine the histological changes with over-exercise.
Normal rat Achilles tendons were assayed via: hydroxyproline for total collagen, SDS-PAGE electrophoresis for collagen subtypes, thermoelastic testing for immature/mature collagen crosslinking, and tensile mechanical testing. As per Soslowsky in the rat rotator cuff, the over-exercise model used 10° uphill treadmill running over twelve weeks. Light histology under H& E staining and birefringence was assessed using a blinded, semi-quantitative scale.
The normal rat Achilles is 89.6 ± 10.6% (SD) collagen with a mean UTS of 5.29 ± 1.91 MPa (SD). Only type I collagen is evident in SDS-PAGE and immature collagen crosslinking is dominant demonstrated by
NaBH4-reduction required to achieve a 90°C isotherm
in hydrothermal testing. The three, six and twelve-week over-exercise regimes produce increasing cell area density and decreasing collagen organization. Surprisingly, the proliferating cells do not seem to be fibroblast dominant and label with factor III antibody to human endothelial cells.
The normal Achilles tendon in young (eight weeks old) but mature rats is a strong, collagen-rich tissue; however, immature crosslinking suggests remodelling. We suspect that low type III collagen in the normal Achilles may increase significantly with inflammation. However, fibroblast proliferation may not be dominant.
Our rat Achilles tendon over-exercise model has demonstrated histopathology consistent with the human literature. With clear structural/mechanical characterization, future studies will focus on changes in these variables with disease tendons derived from the rat ten-dinosis model.
Funding: Research Grants were received from the following organizations: 1-Canadian Orthopaedics Foundation, 2-American Foot and Ankle Society, 3-Dalhousie University Department of Surgery, 4-Nova Scotia Capitol District Health Authority Research Fund
Correspondence should be addressed to Cynthia Vezina, Communications Manager, COA, 4150-360 Ste. Catherine St. West, Westmount, QC H3Z 2Y5, Canada
