Reduced Expression of Insulin-like Growth Factor 1 Receptor Leads to Accelerated Intervertebral Disc Degeneration in Mice

Abstract

Insulin-like growth factor 1 (IGF-1) and its receptor (insulin-like growth factor 1 receptor, IGF1R) can regulate the extracellular matrix synthesis and play a crucial role in maintaining the normal functions of the intervertebral disc (IVD). The objective of this study was to investigate whether there would be accelerated IVD degeneration (IVDD) in IGF1R+/- mice. Three IGF1R+/- male mice and three wild-type male mice were sacrificed respectively at 6, 12, and 18 weeks after birth. Six lumbar disc samples were harvested from each mouse, with a total of 54 disc samples taken from each genotype. Histomorphological analysis for the IVD was performed to assess the degenerative extent according to the classification system proposed by Boos et al. Quantitative real-time PCR and semi-quantitative histologic scoring (HScore) for immunohistochemical staining were used to evaluate the expression level of type-II collagen, aggrecan and matrix metallopeptidase 13 (MMP-13). Histomorphological analysis for the discs revealed significantly less amounts of proteoglycan and type-II collagen, and significantly higher total degenerative score in IGF1R+/- mice than in wild-type mice. Real-time PCR showed that the mRNA expressions of type-II collagen and aggrecan in the discs were significantly lower, while MMP-13 was significantly higher in IGF1R+/- mice than in wild-type mice. The results of HScore analysis were similar to those obtained from the quantitative real-time PCR. Taken together, our study indicates that reduced expression of IGF1R would lead to accelerated degeneration of IVD. IGF1R+/- mice could be regarded as a good animal model to study IVD degeneration (IVDD), and studies on the IVD of IGF1R+/- mice could provide further insight into the pathogenesis of IVDD.