Effect of Transgenic IGF-I Over-Expression on Tooth and Alveolar Structures

Introduction: Insulin-like growth factors (IGFs) are a family of proteins that control growth and differentiation in numerous tissues. In the developing tooth, IGF-I and IGF-1R are synthesized locally by ameloblasts and secretory and maturing odontoblasts. IGF-I induces cellular differentiation in explanted dental papillae and dental pulp. However, little is known about the mechanisms by which IGF-I stimulates dentin formation and odontoblast differentiation. Objective: To characterize the effects of IGF-I overexpression on the formation of dentin and alveolar bone in pOBCol3.6-IGF transgenic (TG) mice in which IGF-I expression is driven by a 3.6-kb fragment of the rat Col1a1 promoter. Methods: The micro-architecture of the alveolar bone, first molar and incisor of TG and wild type (WT) littermates was examined at 4 and 8 weeks of age using micro-computed tomography (MicroCT). At each time point, 7-9 mandibles isolated from WT and TG were analyzed. Results: MicroCT showed that IGF-I overexpression increased the size and surface area of molar and incisor tooth structures. The change in size was due to an increase in dentin volume with no accompanying change in enamel volume. Both the total tissue volume (TV) and bone volume (BV) of the alveolar region were increased in TG mice, but there was no change in the alveolar bone volume fraction (BV/TV%). Results were consistent at both age points. Conclusions: Targeted overexpression of IGF-I with a 3.6-kb rat Col1a1 promoter fragment resulted in increases in the thickness of dentin in both incisors and molar without influencing the enamel. pOBCol3.6-IGF TG mice did not exhibit changes in the alveolar bone. Supported by NIH grants DE016689 & DE007302.