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Updated: Jul 17, 2026
Biomechanical Testing of Murine Tendons
Published on: October 15, 2019
Matrix metalloproteinase inhibitors prevent a decrease in the mechanical properties of stress-deprived tendons: an in
Steven P Arnoczky1, Michael Lavagnino, Monika Egerbacher
1Laboratory for Comparative Orthopaedic Research, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA. arnoczky@cvm.msu.edu
Background:
An increase in matrix metalloproteinases (MMPs) and the resulting degradation of the extracellular matrix have been implicated in the pathogenesis of tendinopathy. Studies have documented the beneficial effects of MMP inhibitors used to treat pathologic conditions in which MMP activity has had a negative effect on connective tissues.
Hypothesis:
Matrix metalloproteinase inhibitors will prevent the decrease in material properties associated with tendon stress deprivation by inhibiting MMP activity.
Study Design:
Controlled laboratory study.
Methods:
Rat tail tendons were subjected to 7 days of in vitro stress deprivation with and without the addition of 1 of 2 broad-spectrum MMP inhibitors (doxycycline and ilomastat). The material properties (ultimate tensile stress, strain, and tensile modulus) of the tendons were compared with each other and with fresh control tendons. In addition, tendons from each group were evaluated for MMP-13 messenger RNA expression, MMP-13 protein synthesis, MMP-13 activity, and pericellular matrix morphology.
Results:
Both MMP inhibitors resulted in a statistically significant reduction in MMP activity in 7 day stress-deprived tendons when compared with nontreated, stress-deprived tendons. Similarly, tendons treated with either ilomastat or doxycycline had significantly improved material properties. MMP-13 messenger RNA expression and protein synthesis were not significantly affected by either MMP inhibitor. Both MMP inhibitors were able to maintain the integrity of the pericellular matrix when compared with nontreated, stress-deprived tendons.
Conclusion:
Matrix metalloproteinase inhibitors prevented the activation of MMP-13 and significantly inhibited pericellular matrix degeneration and the loss of material properties associated with stress deprivation.
Clinical Relevance:
Matrix metalloproteinase inhibitors may play a supportive role in the treatment of tendinopathy by limiting the MMP-mediated degradation of the extracellular matrix.
Insights
Matrix metalloproteinase inhibitors protected tendon material properties and pericellular matrix integrity during stress deprivation. These findings suggest MMP inhibitors may aid in treating tendinopathy by limiting matrix degradation.
Area of Science:
- Biomaterials Science
- Connective Tissue Biology
- Pharmacology
Background:
- Increased matrix metalloproteinases (MMPs) contribute to tendinopathy pathogenesis.
- MMP inhibitors have shown benefits in conditions affecting connective tissues.
Purpose of the Study:
- To investigate if matrix metalloproteinase inhibitors prevent material property decline in stressed tendons.
- To assess the impact of MMP inhibitors on tendon stress deprivation.
Main Methods:
- Rat tail tendons underwent 7 days of in vitro stress deprivation.
- Treated tendons received doxycycline or ilomastat, broad-spectrum MMP inhibitors.
- Evaluated material properties, MMP-13 expression, protein synthesis, activity, and matrix morphology.
Main Results:
- MMP inhibitors significantly reduced MMP activity and preserved tendon material properties.
- Ilomastat and doxycycline maintained pericellular matrix integrity.
- MMP-13 gene and protein expression were not significantly altered.
Conclusions:
- MMP inhibitors prevent MMP-13 activation, matrix degeneration, and loss of material properties.
- MMP inhibitors may support tendinopathy treatment by mitigating MMP-mediated extracellular matrix degradation.
