Regulation of IGF-I by IGFBP3 and IGFBP5 during odontoblast differentiation in mice

Abstract

ObjectivesAlthough intracellular signaling pathways of insulin-like growth factor I (IGF-I) related to the proliferation of dental pulp cells have been investigated, the switching mechanism from cell proliferation to differentiation during odontogenesis remains elusive. This study aimed to elucidate the role of IGF binding protein (IGFBP) 3 and 5 in regulation of IGF-I during odontoblast differentiation in mouse incisors. MethodsThe detailed expression patterns of IGF-I, IGF-I receptor (IGF-IR), IGFBP3, and IGFBP5 together with that of an odontoblast differentiation marker, nestin, were examined by immunohistochemistry and/or in situ hybridization using paraffinized sections of TetOP-H2B-GFP mouse incisors at postnatal 4 weeks. ResultsUndifferentiated dental papilla cells and preodontoblasts (preOB) showed intense IGF-I- and IGF-IRα-positive reactions, and the expression was observed in differentiated odontoblasts, such as immature odontoblasts (iOB) and mature odontoblasts (mOB). IGFBP3/Igfbp3 was transiently expressed in preOB and early iOB, and the intensity of expression gradually reduced with the progression of odontoblast differentiation. In contrast, immunohistochemical analysis for IGFBP5 identified a positive reaction in the undifferentiated dental papilla cells and differentiated odontoblasts, and the expression of Igfbp5 was reduced in the differentiated odontoblasts. ConclusionThe present study demonstrated the expression patterns of IGF-I, IGF-IR, IGFBP3, and IGFBP5 during odontoblast differentiation in mouse incisors. These results suggested that IGFBP3 regulates the transition from the proliferative to differentiation stage by inhibiting the action of IGF-I on the proliferation of dental papilla cells, and that IGFBP5 plays an important role in the maintenance of the differentiated odontoblasts during tooth development.