PAPP-A affects tendon structure and mechanical properties

Pregnancy-associated plasma protein-A (PAPP-A) serves to increase local insulin-like growth factor (IGF) stimulation of proliferation and differentiation in many tissues through proteolysis of inhibitory IGF-binding proteins. The purpose of this study was to investigate the effects of PAPP-A on tendon structure and mechanical properties. A total of 30 tails from 6-month-old mice were tested with 10 tails in each of following groups: PAPP-A knockout (KO), skeletal-specific PAPP-A overexpressing transgenic (Tg) and wild type (WT). Morphologically, the total tail cross-sectional area (CSA), individual tissue CSAs of bone, muscle and tendon, and fascicle diameter were measured. A fascicle pullout test was performed to assess stiffness and strength of interfascicular structures. Fascicles were mechanically characterized through low and high displacement rate uniaxial tension tests providing modulus at each rate, hysteresis area and stress relaxation ratio. The KO mice had a smaller total tail CSA (p< 0.05), fascicle diameter (p< 0.05), absolute tendon CSA (p< 0.05), fast and slow stiffness (p< 0.05 for both) and larger hysteresis area (p< 0.05) compared to WT and Tg mice. On the other hand, the Tg mice had a larger fascicle diameter (p< 0.05), absolute tendon CSA (p< 0.05), higher interfascicular strength and stiffness (p< 0.05) and lower fascicular modulus at low displacement rates (p< 0.05) compared to WT and KO mice. Tg mice also had larger total tail CSA area (p< 0.05) and smaller hysteresis area (p< 0.05) than KO mice, and larger normalized tendon CSA (p< 0.05) than WT mice. Based on these data, we conclude that PAPP-A affects fascicle structure, thereby affecting tendon phenotype.