Deficiency of macrophage migration inhibitory factor gene delays healing of the medial collateral ligament: a biomechanical and biological study.
The role played by macrophage migration inhibitory factor (MIF) in the process of wound healing is controversial. Besides, there have been no reports that investigated the expression or the role of MIF in the repair process after ligament injury. In this study, we hypothesized that the deficiency in MIF gene might delay ligament healing in mice. The aim of this study was to clarify this hypothesis using MIF gene-deficient mice (MIFKO) and murine model of injury to the medial collateral ligament (MCL). Biomechanical testing showed that the levels of mechanical properties were significantly lower in MIFKO than in wild-type mice (WT) on day 28 after injury. Levels of matrix metalloproteinase (MMP)-2 and -13 mRNA in the healing tissue were significantly lower in MIFKO than in WT on day 28 and on day 7, respectively. Histologically, healing tissues in MIFKO exhibited prolonged hypertrophy, poor vascularity, and prolonged increase in cell number compared with those in WT. Taken together, it was suggested that MIFKO exhibited delayed healing of the MCL, which might be caused by lower mRNA expression of MMP-2 and -13.
Department of Sports Medicine and Joint Reconstruction Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Soichiro
S
Kitayama
Shin
S
Onodera
Eiji
E
Kondo
Takumi
T
Kobayashi
Shin
S
Miyatake
Nobuto
N
Kitamura
Harukazu
H
Tohyama
Kazunori
K
Yasuda
D000818:Animals; D001696:Biomechanical Phenomena; D017885:Collateral Ligaments / Q000378:metabolism / Q000473:pathology; D005260:Female; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics* / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D017888:Medial Collateral Ligament, Knee / Q000473:pathology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics
D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D020778:Matrix Metalloproteinase 2; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse