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Dystrophic tendon functionality is recovered by muscle-specific expression of insulin-like growth factor in mdx mice.

Abstract : Duchenne muscular dystrophy (DMD) is a severe genetic disorder of skeletal muscle, characterized by a steady muscle weakness. By using the animal model for DMD, the mdx mice, we have previously demonstrated that biomechanical properties of tendinous tissue are also significantly affected in this muscle pathology. Muscle specific over-expression of insulin like growth factor-1 (mIgf-1) is known to induce a partial recovery in muscle functionality, in particular increasing the muscle absolute force, but not the specific force. To test whether Igf-1 muscle specific over-expression helps the recovery also in tendinous tissue, mechanical and cellular evaluation of mdx and mdx:MLC/mIgf-1 mice tendons has been performed. Mechanical properties were investigated by measuring the viscoelastic response of the tissue, while cell viability was evaluated by molecular assays. An absolute recovery in the mechanical properties of EDL and TA tendons was observed through the measurement of tissue viscoelasticity for several different frequencies of interest. Moreover, when compared with tendons from dystrophic mdx animals, mdx:MLC/mIgf-1 specimens showed an almost complete recovery in the number of viable cells for both extensor digitorum longus (EDL) and tibialis anterior (TA) tendons. Of note, the partial recovery in muscle functionality and the full recovery in tendons response, suggests that mIgf-1 muscle specific over-expression exerts its effect on tendons either indirectly, improving the tendon viability and its functional properties as a consequence of the reduction of the hostile muscle dystrophic environment, or acting directly on the tendon tissue, as a paracrine trophic factor.
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Submitted on : Tuesday, July 22, 2014 - 9:55:29 AM
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E Rizzuto, A Catizone, A Musarò, Z del Prete. Dystrophic tendon functionality is recovered by muscle-specific expression of insulin-like growth factor in mdx mice.. Journal of Biomechanics, Elsevier, 2013, 46 (3), pp.604-7. ⟨10.1016/j.jbiomech.2012.10.007⟩. ⟨pasteur-01027483⟩



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