Ligament healing is composed of several phases, including acute inflammation and reaction phase, repair and regeneration phase, and remodeling phase. At the molecular level, these phases are regulated by a complex interplay among inflammatory cells, fibroblasts, and the molecules, such as inflammatory cytokines, proteinases, extracellular matrices, and etc, which are produced by these cells. Macrophage migration inhibitory factor (MIF), which was discovered in 1966 as the first lymphokine, has been recognized as a pivotal mediator of inflammation in various pathological conditions including sepsis, arthritis, ARDS, and etc. Recent studies have shown that MIF plays an important role in proliferation and differentiation of cells, generation of organs, and wound healing 1-3. However, a role of MIF on the ligament healing process has not been elucidated as of yet. Based on the abovedescribed knowledge, we have hypothesized that MIF may enhance healing of the injured medial collateral ligament (MCL). Recently, a murine MCL injury model has attracted much notice because it is useful to clarify the effect of specific factor ablation on MCL healing by using genetically altered mice 4. A specific hypothesis to be tested in this study using MIF gene-deficient (MIF KO) mice is that the genetic ablation of MIF may inhibit natural improvement of the structural and mechanical properties of the injured MCL.
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