Deficiency of macrophage migration inhibitory factor gene delays healing of the medial collateral ligament: A biomechanical and biological study

Abstract

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.

Instrument-assisted cross fiber massage increases tissue perfusion and alters microvascular morphology in the vicinity of healing knee ligaments

“…Each stage of ligament healing depends upon adequate vascularity and blood flow for the delivery and removal of cells and metabolic substrates at the injury site [20]. Numerous studies have associated variations in blood supply with alterations in knee MCL healing [25-28], and differences in blood supply are thought to contribute to the differential healing of MCL and anterior cruciate ligament injuries [29,30]. Massage therapy is often introduced with the intent of altering tissue blood flow; however, studies have generally been limited to the exploration of immediate, short-term effects [31-34].…”