[P3-0788] Skeletal muscle regeneration is delayed in midkine-deficient mice
キーワード：skeletal muscle, regeneration, Midkine
【Purpose】
Physical Therapists provide rehabilitation to the patients who injured muscles by an accident or sports injury or surgery. Therefore, it is necessary to know the process of muscle degeneration and regeneration. Midkine（MK）, a heparin-binding growth factor, was previously found to be expressed in the rat myotube-forming stage. We investigated MK gene-deficient（Mdk（-/-））mice in terms of skeletal muscle degeneration and regeneration after injury
【Methods】
A role of MK in regeneration of skeletal muscle was explored comparing wild type（Mdk（+/+））with Mdk（-/-）mice after injury by bupivacaine injection into the tibialis anterior muscle. The evaluation of muscle regeneration was assessed by measuring cross sectional area of each myotubes using HE staining. And we observed regeneration process and assessed inflammatory response by immunohistochemical analysis.
【Results】
Injured muscles showed intense inflammatory cell infiltration. MK were expressed in a part of activated satellite cells and desmin-positive myotubes, myofibers with centrally located nuclei in their cytoplasm, in Mdk（+/+）mice. Myotubes were significantly smaller in Mdk（-/-）mice than in Mdk（+/+）mice 7 days after injury（p=0.02）. The distribution of myotube sizes showed quantitative differences between the two groups at 5 and 7 days, but not at 14 days. Many small myotubes were found in the regenerative area of Mdk（-/-）mice compared with that of Mdk（+/+）mice 5 and 7 days after injury. The expression of Iba1, a macrophage marker, was significantly lower in Mdk（-/-）mice 3 days after injury（p=0.01）. The number of desmin-positive cells like myoblasts in Mdk（-/-）mice was significantly fewer than that in Mdk（+/+）mice 3 days after injury.
【Discussion】
Our results suggested that deletion of MK results in a delay in regeneration, preceded by decelerated migration of macrophges to the damaged area, and that MK has a role in cell differentiation and maturation after skeletal muscle injury.
Physical Therapists provide rehabilitation to the patients who injured muscles by an accident or sports injury or surgery. Therefore, it is necessary to know the process of muscle degeneration and regeneration. Midkine（MK）, a heparin-binding growth factor, was previously found to be expressed in the rat myotube-forming stage. We investigated MK gene-deficient（Mdk（-/-））mice in terms of skeletal muscle degeneration and regeneration after injury
【Methods】
A role of MK in regeneration of skeletal muscle was explored comparing wild type（Mdk（+/+））with Mdk（-/-）mice after injury by bupivacaine injection into the tibialis anterior muscle. The evaluation of muscle regeneration was assessed by measuring cross sectional area of each myotubes using HE staining. And we observed regeneration process and assessed inflammatory response by immunohistochemical analysis.
【Results】
Injured muscles showed intense inflammatory cell infiltration. MK were expressed in a part of activated satellite cells and desmin-positive myotubes, myofibers with centrally located nuclei in their cytoplasm, in Mdk（+/+）mice. Myotubes were significantly smaller in Mdk（-/-）mice than in Mdk（+/+）mice 7 days after injury（p=0.02）. The distribution of myotube sizes showed quantitative differences between the two groups at 5 and 7 days, but not at 14 days. Many small myotubes were found in the regenerative area of Mdk（-/-）mice compared with that of Mdk（+/+）mice 5 and 7 days after injury. The expression of Iba1, a macrophage marker, was significantly lower in Mdk（-/-）mice 3 days after injury（p=0.01）. The number of desmin-positive cells like myoblasts in Mdk（-/-）mice was significantly fewer than that in Mdk（+/+）mice 3 days after injury.
【Discussion】
Our results suggested that deletion of MK results in a delay in regeneration, preceded by decelerated migration of macrophges to the damaged area, and that MK has a role in cell differentiation and maturation after skeletal muscle injury.