1. Different mechanisms activated by mild versus strong loading in rat Achilles tendon healing
- Author
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Hammerman, Malin, Dietrich, Franciele, Blomgran, Parmis, Eliasson, Pernilla T., and Aspenberg, Per
- Subjects
Fysiologi ,Physiology ,Immunology ,Toxic Agents ,Bacterial Toxins ,lcsh:Medicine ,Gene Expression ,Botulinum Toxin ,Pathology and Laboratory Medicine ,Toxicology ,Achilles Tendon ,Blood Plasma ,Rats, Sprague-Dawley ,Tendons ,Random Allocation ,Signs and Symptoms ,Tendon Injuries ,Diagnostic Medicine ,Elastic Modulus ,Tissue Repair ,Medicine and Health Sciences ,Genetics ,Animals ,Toxins ,lcsh:Science ,Immune Response ,Inflammation ,Wound Healing ,lcsh:R ,Biology and Life Sciences ,Cell Biology ,Biomechanical Phenomena ,Body Fluids ,Extracellular Matrix ,Disease Models, Animal ,Biological Tissue ,Blood ,Gene Expression Regulation ,Connective Tissue ,lcsh:Q ,Female ,Anatomy ,Cellular Structures and Organelles ,Physiological Processes ,Research Article - Abstract
Background Mechanical loading stimulates Achilles tendon healing. However, various degrees of loading appear to have different effects on the mechanical properties of the healing tendon, and strong loading might create microdamage in the tissue. This suggests that different mechanisms might be activated depending on the magnitude of loading. The aim of this study was to investigate these mechanisms further. Methods Female rats had their right Achilles tendon cut transversely and divided into three groups: 1) unloading (calf muscle paralysis by Botox injections, combined with joint fixation by a steel-orthosis), 2) mild loading (Botox only), 3) strong loading (free cage activity). Gene expression was analyzed by PCR, 5 days post-injury, and mechanical testing 8 days post-injury. The occurrence of microdamage was analyzed 3, 5, or 14 days post-injury, by measuring leakage of injected fluorescence-labelled albumin in the healing tendon tissue. Results Peak force, peak stress, and elastic modulus of the healing tendons gradually improved with increased loading as well as the expression of extracellular matrix genes. In contrast, only strong loading increased transverse area and affected inflammation genes. Strong loading led to higher fluorescence (as a sign of microdamage) compared to mild loading at 3 and 5 days post-injury, but not at 14 days. Discussion Our results show that strong loading improves both the quality and quantity of the healing tendon, while mild loading only improves the quality. Strong loading also induces microdamage and alters the inflammatory response. This suggests that mild loading exert its effect via mechanotransduction mechanisms, while strong loading exert its effect both via mechanotransduction and the creation of microdamage. Conclusion In conclusion, mild loading is enough to increase the quality of the healing tendon without inducing microdamage and alter the inflammation in the tissue. This supports the general conception that early mobilization of a ruptured tendon in patients is advantageous. Funding Agencies|Swedish Research Council; Swedish Research Council for Sports Science; Ostergotland County (ALF)
- Published
- 2018