IGF-1 and bone: New discoveries from mouse models

Abstract

Insulin-like growth factor-1 (IGF-1) plays a central role in cellular growth, differentiation, survival, and cell cycle progression. It is expressed early during development and its effects are mediated through binding to a tyrosine kinase receptor, the insulin-like growth factor-1 receptor (IGF-1R). In the circulation, the IGFs bind to IGF-binding proteins (IGFBPs), which determine their bioavailability and regulate the interaction between the IGFs and IGF-1R. Studies in animal models and in humans have established critical roles for IGFs in skeletal growth and development. In this review we present new and old findings from mouse models of the IGF system and discuss their clinical relevance to normal and pathological skeletal physiology.

Fig. 1

(A) Relative cortical area (RCA = Ct.Ar./Tt.Ar.) versus body weight for male LID and control mice during growth, as published previously.(49) (B) RCA versus body weight for male ALS KO and control mice during growth, as published previously.(50) For both LID and ALS KO mice, RCA is increased as body weight increases during growth compared with control mice, illustrating a small compensatory response of bone to decreased periosteal apposition.