Transgenic Expression of Human IGF1 in Intervertebral Degenerative Discs

Abstract

This study investigated the role of human insulin-like growth factor-1 (hIGF-1; encoded by the hIGF1 gene) on intervertebral disc degeneration. A total of 24 male New Zealand rabbits of an intervertebral disc degeneration (IVDD) model were randomly divided into three groups where the following were injected into the lumbar 4 – 5 and 5 – 6 discs: second generation adenovirus containing cytomegalovirus hIGF1 (Ad/CMV- hIGF1); 100 μg/l hIGF-1 protein; or phosphate-buffered saline. At 1, 2, 4 and 8 weeks post-injection, intervertebral disc samples were harvested. Human IGF-1 protein was detected using Western blot analysis, and aggrecan and collagen type II gene fragments were quantified using reverse transcription—polymerase chain reaction. At week 1 post-injection, hIGF-1 protein levels were similar in the Ad/CMV- hIGF1 and hIGF-1 groups. By week 2 the level had decreased substantially in the hIGF-1 group. At week 4 it was still present in the Ad/CMV- hIGF1 group and, by week 8, no protein was detected in any of the three groups. Aggrecan and collagen type II mRNA levels increased in the Ad/CMV- hIGF1 group 1 – 4 weeks post-injection, but declined by week 8, while both decreased steadily over 8 weeks in the other two groups. In conclusion, hIGF1 gene expression lasted for 4 weeks and stimulated the synthesis of aggrecan and collagen type II in the Ad/CMV- hIGF1 group.