Publication Date

2010

Document Type

Honors Thesis

Department

Engineering

Keywords

Achilles tendon, Protein deficiency-Physiological effect, Myostatin, Tendon, Biomechanics, GDF-8, Mouse

Abstract

Myostatin (MSTN) is a secreted protein that acts as a negative regulator of skeletal muscle growth. Deficiencies in this protein have been shown to increase muscle mass in a variety of animal models. Consequently, clinical suppression of myostatin is now being pursued as a therapeutic strategy to counteract the muscle wasting that occurs in patients with degenerative neuromuscular diseases such as Duchenne Muscular Dystrophy (DMD). Although research supports the use of myostatin suppression therapy to increase muscle mass, investigation into the effects of myostatin on tendon is limited. The aim of this study was to investigate the effects of myostatin deficiency by characterizing the structural, material and compositional properties of the Achilles tendons from mature (16 week old) male myostatin deficient (MSTN-/-), wild type (MSTN+/+), and heterozygous (MSTN+/-) mice. Specifically, we tested the hypothesis that myostatin deficiency is associated with stiffer and stronger tendons, that these effects are dose dependent, and that structural and material differences can be explained by differences in tendon composition. The experimental model consisted of sixty male mice, thirty of which were used for Achilles tendon tensile mechanical testing and thirty for tendon biochemical compositional analysis. Results demonstrated that there were no significant differences in tendon geometric, structural or material properties. There was a statistically significant difference in total body mass, with a larger mass in the myostatin null group, but there was no difference in Achilles tendon wet weight itself. DNA, glycosaminoglycan (GAG), and hydroxyproline (indicative of total collagen) content were also assessed. Myostatin null animals were found to have less DNA per wet weight, but more GAG per cell than their wild type counterparts. There were no significant differences in collagen between any of the genotypes. These data do not support the conclusion that myostatin deficiency causes stiffer and stronger tendons, but suggest that myostatin levels have no effect on mature mouse Achilles tendon mechanical properties. Further study is necessary to better understand the role of myostatin in tendon composition and mechanical function.

Language

English

Comments

vi, 78 p. : ill. (some col.) Honors Project-Smith College, Northampton, Mass., 2010. Includes bibliographical references (p. 43-46)

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