The influence of fibrillin-1 and physical activity upon tendon tissue morphology and mechanical properties in mice

Peter H.T. Tran, Tanja Skrba, Elisabeth Wondimu, Giuseppina Galatioto, René Brüggebusch Svensson, Annesofie T. Olesen, Abigail L. Mackey, S. Peter Magnusson, Francesco Ramirez, Michael Kjaer

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8 Scopus citations

Abstract

Fibrillin-1 mutations cause pathological changes in connective tissue that constitute the complex phenotype of Marfan syndrome. In this study, we used fibrillin-1 hypomorphic and haploinsufficient mice (Fbn1mgr/mgR and Fbn1+/− mice, respectively) to investigate the impact of fibrillin-1 deficiency alone or in combination with regular physical activity on tendon tissue morphology and mechanical properties. Morphological and biomechanical analyses revealed that Fbn1mgr/mgR but not Fbn1+/− mice displayed smaller tendons with physical properties that were unremarkable when normalized to tendon size. Fbn1mgR/mgR mice (n = 43) Fbn1+/−mice (n = 27) and wild-type mice (WT, n = 25) were randomly assigned to either control cage conditions (n = 54) or to a running on a running wheel for 4 weeks (n = 41). Both fibrillin-1-deficient mice ran voluntarily on the running wheel in a manner similar to WT mice (3–4 km/24 h). Regular exercise did not mitigate aneurysm progression in Fbn1mgR/mgR mice (P < 0.05) as evidenced by unmodified median survival. In spite of the smaller size, tendons of fibrillin-1-deficient mice subjected to regular exercise showed no evidence of overt histopathological changes or tissue overload. We therefore concluded that lack of optimal fibrillin-1 synthesis leads to a down regulation of integrated tendon formation, rather than to a loss of tendon quality, which also implies that fibrillin-1 deficiency in combination with exercise is not a suitable animal model for studying the development of tendon overuse (tendinopathy).

Original languageEnglish
Article numbere14267
JournalPhysiological Reports
Volume7
Issue number21
DOIs
StatePublished - 1 Nov 2019

Keywords

  • Biomechanics
  • Exercise
  • Marfan
  • Survival
  • Tendinopathy

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