TY - JOUR

T1 - The influence of fibrillin‐1 and physical activity upon tendon tissue morphology and mechanical properties in mice

AU - Tran, Peter H. T.

AU - Skrba, Tanja

AU - Wondimu, Elisabeth

AU - Galatioto, Giuseppina

AU - Svensson, René Brüggebusch

AU - Olesen, Annesofie T.

AU - Mackey, Abigail L.

AU - Magnusson, S. Peter

AU - Ramirez, Francesco

AU - Kjaer, Michael

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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 (Fbn1(mgr/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 Fbn1(mgr/mgR) but not Fbn1(+/-) mice displayed smaller tendons with physical properties that were unremarkable when normalized to tendon size. Fbn1(mgR/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 Fbn1(mgR/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).

AB - 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 (Fbn1(mgr/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 Fbn1(mgr/mgR) but not Fbn1(+/-) mice displayed smaller tendons with physical properties that were unremarkable when normalized to tendon size. Fbn1(mgR/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 Fbn1(mgR/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).

U2 - 10.14814/phy2.v7.21

DO - 10.14814/phy2.v7.21

M3 - Journal article

VL - 7

JO - Physiological Reports

JF - Physiological Reports

SN - 2051-817X

IS - 21

M1 - e14267

ER -