Skeletal Muscle Changes And The Effects Of IGF-1 On It During Distraction Osteogenesis

Background: Distraction osteogenesis(DO) is a surgical technique utilized for limb length discrepancies or skeletal deformities caused by trauma, infection or malignancies. DO is used forming new bone between bone segments to lengthen callus throuth slow distraction. However soft tissues, especially skeletal muscle often failed to adapt to distraction and causes some complications. Insulin-like growth factor-1(IGF-1), as a kind of growth factors wildly in human body, has been implicated as a central regulator of muscle repair. This study is to evaluate the change of tibialis anterior muscle(TA muscle) and gastrocnemius(GS) during tibia distraction osteogenesis and to investigate whether IGF-1 injection could improve the ability of adaption of GS in DO.Methods:(1) we used eighty eight-week old S-D rats to create the model of tibia distraction osteogenesis. All the animals were equally divided into control group and distraction group randomly. TA muscle and GS were harvested at 1st, 4th, 7th, 10 th day during DO. Length and weight of muscles, cross-sectional area of muscle fibers(FCSA), maximum limit load(MLL) and passive stiffness of muscle and gene expression of Myo D, myogenin, myostatin were analyzed.(2) A total of 102 Sprague-Dawley rats received DO or did not were randomly assigned into saline, IGF-1 groups. On the day before the distraction, the rats in the IGF-1 group were injected with IGF-1, then injected every other day. Rats in saline group were injected with saline at the same time and same volume as ones in IGF-1 group. The gastrocnemius muscles of the rats were harvested at the 0, 1st, 4th, 7th and 10 th days of distraction. The weight of the muscles, cross-sectional area(CSA) of the muscle fibers, collagen volume fraction(CVF), maximum limit load(MLL), maximum contraction forces and gene expression of Akt, Myo D, myogenin, myostatin and collagen I were analyzed. The results indicated that IGF-1 injection had increased the weights, CSA of the muscle fibers, MLL and force generation of the gastrocnemius.Result:(1) Weight of TA muscle and GS increased but were below the normal ones during DO. In distraction group, MLL of TA muscle increased significantly, while GS had a little decline. Passive stiffness of both kinds of muscle increased. Myo D and myogenin were upregulated and myostatin was downregulated.(2) The results indicated that IGF-1 injection had increased the weights, CSA of the muscle fibers, MLL and force generation of the gastrocnemius. Also, Akt, Myo D and myogenin were upregulated, and myostatin was downregulated in the IGF-1 group.Conclusions:(1) DO can negatively change the morphology and mechanical properties of TA muscle and GS and regulate the relate m RNA. TA muscle better adapts to during DO than GS.(2) IGF-1 injection could improve the ability of adaption of GS in DO. Injection of exogenous IGF-1 could attenuate the gastrocnemius atrophy, prevent fibrosis, increase MLL. The effect of IGF-1 injection on GS is achieved by regulation of related m RNA expression.