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Medial collateral ligament healing in macrophage metalloelastase (MMP‐12)‐deficient mice
Author(s) -
Wright Rick W.,
Allen Tracy,
ElZawawy Hossam B.,
Brodt Michael D.,
Silva Matthew J.,
Gill Corey S.,
Sandell Linda J.
Publication year - 2006
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.20222
Subject(s) - medial collateral ligament , in situ hybridization , medicine , wound healing , matrix metalloproteinase , macrophage , immunohistochemistry , pathology , ligament , andrology , anatomy , messenger rna , surgery , chemistry , in vitro , biochemistry , gene
Medial collateral ligament (MCL) injuries heal by a wound repair scar response controlled by 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 of the 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 Col1a1 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 stiffness ( 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. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:2106–2113, 2006