Medial collateral ligament healing in macrophage metalloelastase (MMP-12)-deficient mice

Rick W. Wright, Tracy Allen, Hossam B. El-Zawawy, Michael D. Brodt, Matthew J. Silva, Corey S. Gill, Linda J. Sandell

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11 Scopus citations

Abstract

Medial collateral ligament (MCL) injuries heal by a wound repair sear response controlled a complex cellular and cytokine environment. Many enzymes participate in wound repair, particularly the matrix metalloproteinases. We hypothesize macrophage metalloelastase (MME/MMP-12) deficiency results in impaired healing of MCL injury. One hundred fifty MME-deficient and 150 WT (MME+/+) mice underwent knee MCL transection with the opposite knee as a sham operated control. Mice were sacrificed at 3,7,28,42, and 56 days. At each ofthe five time points, 15 mice were utilized for biological and 15 were utilized for biomechanical testing. Outcome measures were the presence of macrophages to represent the inflammatory phase of wound healing, collagen synthesis to assay for matrix repair, and biomechanical testing for repair strength. Immunohistochemistry demonstrated significantly fewer macrophages in cut MCLs from MME-deficient mice versus wild-type (WT) mice at 3, 7, 28, and 42 days (all p ≤ 0.04). In situ hybridization to Collal mRNA in the MME-deficient cut MCLs at 7, 28, and 42 day time points showed a decreased level of type I pro-collagen mRNA compared to the WT cut MCLs (p < 0.05). Biomechanical testing revealed cut ligaments from MME-deficient mice had significantly lower ultimate force and stiffness compared to cut ligaments from WT mice (p < 0.001), with maximal differences of 40% at 7 days for ultimate force and 28 days for stiffhess (p < 0.05 by Tukey post hoc test). We conclude MME is important in the multifactorial cascade of knee MCL injury healing, showing significant differences in both the early inflammatory and in the matrix tissue synthesis phases.

Original languageEnglish
Pages (from-to)2106-2113
Number of pages8
JournalJournal of Orthopaedic Research
Volume24
Issue number11
DOIs
StatePublished - Nov 1 2006

Keywords

  • Knee
  • Macrophage metalloelastase
  • Medial collateral ligamen
  • Mouse

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    Wright, R. W., Allen, T., El-Zawawy, H. B., Brodt, M. D., Silva, M. J., Gill, C. S., & Sandell, L. J. (2006). Medial collateral ligament healing in macrophage metalloelastase (MMP-12)-deficient mice. Journal of Orthopaedic Research, 24(11), 2106-2113. https://doi.org/10.1002/jor.20222