Systemic stiffening of mouse tail tendon is related to dietary advanced glycation end products but not high-fat diet or cholesterol.

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.