Stimulation of osteogenesis with pro-IGF-2E and IGFBP-2 in a critical-sized bone defect in the rat.

Abstract

Differences in molecular structure of pro-insulin-like growth factor-ΠE in hepatitis-C associated osteosclerosis (elevated levels of pro-insulin-like growth factor-ΠE[68-104]) and non-islet-cell tumor induced hypoglycemia (elevated levels of pro-insulin-like growth factor-ΠE[68-88]), without osteosclerosis, suggest that pro-insulin-like growth factor-ΠE[68-104] can stimulate osteoblasts to bone formation. Treating bone deficits is a major topic in orthopedic surgery. The aim of our study was to investigate the biological significance of the E-domain of pro-insulin-like growth factor-Π in relation to bone formation, by means of critical-sized bone defects in rats. After insulin-like growth factor-Π/pro-insulin-like growth factor-ΠE[68-104] treatment, bone volumes in the defects were quantified using micro-computed tomography. In addition, parameters as structure model index and connectivity of the newly formed bone in the defect as well as trabecular thickness, total tissue volume, the ratio of bone volume over total tissue volume and connectivity density in control regions were measured. Administration of both insulin-like growth factor-ΠE[68-104]/insulin-like growth factor binding protein-2 and insulin-like growth factor-Π/insulin-like growth factor binding protein-2 did not result in stimulation of bone formation in the defects. Although not significant, placebo treated rats appeared to have formed the largest amount of bone volume. The parameters measured at control regions also did not show significant differences. Continuous infusion of insulin-like growth factor-ΠE[68-104]/insulin-like growth factor binding protein-2 and insulin-like growth factor-ΠE/insulin-like growth factor binding protein-2 did not stimulate bone healing in a rat critical-sized bone defect model and did not have any significant effect in control regions.