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Updated: Apr 5, 2026
Biomechanical Testing of Murine Tendons
Published on: October 15, 2019
PAPP-A affects tendon structure and mechanical properties
Tai-Hua Yang1, Andrew R Thoreson1, Kai-Nan An1
1Biomechanics Laboratory and Tendon and Soft Tissue Biology Laboratory, Division of Orthopedic Research, Mayo Clinic, Rochester, MN 55905, USA.
Insights
Pregnancy-associated plasma protein-A (PAPP-A) influences tendon structure and mechanical properties. PAPP-A knockout mice showed impaired tendon development, while overexpression enhanced it.
Area of Science:
- Biochemistry
- Musculoskeletal Biology
- Connective Tissue Research
Background:
- Pregnancy-associated plasma protein-A (PAPP-A) is known to enhance insulin-like growth factor (IGF) signaling by degrading IGF-binding proteins.
- This action promotes cell proliferation and differentiation in various tissues.
Purpose of the Study:
- To investigate the specific role of PAPP-A in modulating tendon structure and mechanical characteristics.
- To understand how PAPP-A expression levels impact tendon development and function.
Main Methods:
- Utilized PAPP-A knockout (KO), skeletal-specific overexpression transgenic (Tg), and wild-type (WT) mouse tail models (n=10 per group).
- Assessed morphological parameters including cross-sectional area (CSA) of tail, bone, muscle, and tendon, alongside fascicle diameter.
- Performed fascicle pullout tests and uniaxial tension tests to evaluate stiffness, strength, modulus, hysteresis, and stress relaxation.
Main Results:
- KO mice exhibited reduced tail and tendon CSA, smaller fascicle diameter, decreased stiffness, and increased hysteresis compared to WT and Tg mice.
- Tg mice displayed larger fascicle diameter, increased tendon CSA, enhanced interfascicular strength and stiffness, and altered modulus compared to WT and KO mice.
- Tg mice showed larger total tail CSA and smaller hysteresis than KO mice, and larger normalized tendon CSA than WT mice.
Conclusions:
- PAPP-A significantly influences tendon fascicle structure.
- Modulation of PAPP-A levels directly impacts the overall tendon phenotype, affecting its mechanical properties and structural integrity.
Abstract:
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.
