title: Systemic stiffening of mouse tail tendon is related to dietary advanced glycation end products but not high-fat diet or cholesterol.
abstract: Tendon pathology is related to metabolic disease and mechanical overloading, but the effect of metabolic disease on tendon mechanics is unknown. This study investigated the effect of diet and apolipoprotein E deficiency (ApoE(-/-)) on mechanical properties and advanced glycation end product (AGE) cross-linking of non-weight-bearing mouse tail tendons. Twenty ApoE(-/-) male mice were used as a model for hypercholesterolemia along with 26 wild-type (WT) mice. One-half of the mice from each group was fed a normal diet (ND) and the other half was fed a high-fat diet (HFD) to induce obesity. All were killed at 40 wk, and tail tendon fascicles were mechanically tested to failure and analyzed for AGEs. Diets were also analyzed for AGEs. ApoE(-/-) mice displayed a 14% increase in plateau modulus compared with WT mice (P < 0.05), whereas HFD mice displayed a 13% decrease in plateau modulus (P < 0.05) and a 12% decrease in total modulus (P < 0.05) compared with ND mice. Tail tendons of HFD mice had significantly lower concentrations of AGEs [carboxymethyllysine (CML): 26%, P < 0.0001; methylglyoxal-derived hydroimidazolone 1 (MG-H1): 15%, P < 0.005; pentosidine: 13%, P < 0.0005]. The HFD had ∼44-fold lower content of CML (P < 0.01), ∼29-fold lower content of carboxyethyllysine (P < 0.005), and ∼16-fold lower content of MG-H1 (P < 0.05) compared with ND. ApoE(-/-) increased, whereas HFD decreased mouse tail tendon stiffness. Dietary AGE content may be a crucial determinant for accumulation of AGE cross-links in tendons and for tissue compliance. The results demonstrate how systemic metabolic factors may influence tendon health.
authors.affiliation: Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark;
authors.forename: C
authors.initials: C
authors.lastname: Eriksen
authors.affiliation: Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark;
authors.forename: R B
authors.initials: RB
authors.lastname: Svensson
authors.affiliation: Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, The Netherlands;
authors.forename: J
authors.initials: J
authors.lastname: Scheijen
authors.affiliation: Cluster for Molecular Imaging, Faculty of Health and Medical Sciences and Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Denmark;
authors.forename: A M F
authors.initials: AM
authors.lastname: Hag
authors.affiliation: Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, The Netherlands;
authors.forename: C
authors.initials: C
authors.lastname: Schalkwijk
authors.affiliation: Department of Rehabilitation Medicine, MOVEFIT- Sports medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands; and.
authors.forename: S F E
authors.initials: SF
authors.lastname: Praet
authors.affiliation: Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark;
authors.forename: P
authors.initials: P
authors.lastname: Schjerling
authors.affiliation: Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark;
authors.forename: M
authors.initials: M
authors.lastname: Kjær
authors.affiliation: Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Department of Physical Therapy, Musculoskeletal Rehabilitation Research Unit, Bispebjerg Hospital, Denmark.
authors.forename: S P
authors.initials: SP
authors.lastname: Magnusson
authors.affiliation: Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Department of Physical Therapy, Musculoskeletal Rehabilitation Research Unit, Bispebjerg Hospital, Denmark ccouppe@gmail.com.
authors.forename: C
authors.initials: C
authors.lastname: Couppé
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D013623:Tail / Q000378:metabolism / Q000473:pathology*; D013710:Tendons / Q000378:metabolism / Q000473:pathology*; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D001057:Apolipoproteins E; D004041:Dietary Fats; D017127:Glycation End Products, Advanced; D002784:Cholesterol
keywords: advanced glycation end products; cholesterol; tendon biomechanics