Low-Dose and Short-Duration Matrix Metalloproteinase 9 Inhibition Does Not Affect Adhesion Formation during Murine Flexor Tendon Healing.

Abstract

BACKGROUND:

After flexor tendon injury and repair, adhesion formation is a substantial concern, as it can result in loss of motion and functional disability. Matrix metalloproteinase 9 (Mmp9) is a gelatinase that contributes to degradation of extracellular matrix and is expressed during flexor tendon healing. Mmp9(-/-) mice have accelerated remodeling of adhesions during flexor tendon healing, relative to wild-type mice. The purpose of this study was to investigate whether Ro 32-3555, an Mmp9 inhibitor, can improve flexor tendon healing by limiting adhesion formation or enhancing remodeling of scar tissue during murine flexor tendon healing.

METHODS:

Flexor digitorum longus laceration and repair was performed in female C57BL/6J mice. Mice were treated with vehicle or the Mmp9 inhibitor Ro 32-3555 for 8 days. Analysis was performed for digit range of motion and gliding function, biomechanics, gene expression, and Mmp9 activity.

RESULTS:

An Mmp9 activity assay and zymography confirmed suppression of Mmp9 activity in mice treated with Ro 32-3555. There was no significant difference in tendon gliding or range of motion between vehicle and Ro 32-3555-treated mice. There was also no difference in tendon biomechanical properties between the two groups.

CONCLUSION:

Local inhibition of Mmp9 gelatinolytic activity at the flexor tendon repair site is insufficient to alter adhesion formation, remodeling of adhesions, or mechanical properties of healing murine flexor tendons.

• Authors: Caitlin A Orner, Michael B Geary, Warren C Hammert, Regis J O'Keefe, Alayna E Loiselle
• Journal: Plastic and reconstructive surgery (Plast Reconstr Surg) Vol. 137 Issue 3 Pg. 545e-553e (Mar 2016) ISSN: 1529-4242 [Electronic] United States
• PMID: 26910699 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Imidazoles
• Matrix Metalloproteinase Inhibitors
• Ro 32-3555
• Matrix Metalloproteinase 9

Topics

• Analysis of Variance
• Animals
• Biomechanical Phenomena
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Imidazoles (administration & dosage)
• Matrix Metalloproteinase 9 (drug effects, metabolism)
• Matrix Metalloproteinase Inhibitors (administration & dosage)
• Mice
• Mice, Inbred C57BL
• Random Allocation
• Reference Values
• Tendon Injuries (drug therapy, surgery)
• Tensile Strength (drug effects)
• Tissue Adhesions (drug therapy, enzymology)
• Wound Healing (drug effects, physiology)