Lengthening of mouse hind limbs with local administration of insulin-like growth factor 2

Abstract

BackgroundFor devising potential clinical approaches for limb length discrepancies, we examined local administration of insulin-like growth factor 2 (IGF2). MethodsC57/BL/6 mice (∼ 8 weeks old) were used in this study, and the mice were separated into two groups: an IGF2-treated group and a placebo group. In the IGF2-treated group, IGF2 was locally administered into the distal epiphysis of the left femur, and the right femur was used as a contralateral control. In the placebo group, saline was administered to the left femur as a vehicle control. The left and right tibiae, without any direct intervention, were employed as negative controls. The dosage of IGF2 was 100 μg/kg/day for 5 consecutive days, and bone samples were harvested on Day 14. Microcomputed tomography images did not show any anomaly at the IGF2 or saline injection sites. ResultsIn comparison with the vehicle control as well as the contralateral control, the results revealed that IGF2 significantly lengthened the treated femur, with an elevation of bone mineral density (BMD) as well as bone mineral content (BMC). The increase in the femoral length of the IGF2-treated left limb was 1.6% (p < 0.05) to the vehicle control, and 1.7% (p < 0.05) to the contralateral control. However, the length, BMD, and BMC of the tibiae were not affected by administration of IGF2 or saline. Western blotting analysis demonstrated that this administration of IGF2 upregulated phosphorylation of an extracellular signal-regulated kinase in the treated femur. ConclusionThe current study supports for the first time the potential effectiveness of administration of IGF2 in adjusting limb length discrepancy.