IGF-II and IGFBP-6 in Prenatal Human Tooth and Jaw Development

Objectives: Components of the insulin-like growth factor (IGF) system are involved in orofacial physiology, development and malformation. IGF-II and its high affinity binding protein, IGFBP-6, are important for developmental processes, where they regulate e.g. proliferation. IGFBP-6 has an inhibitory function on IGF-II. However, no data concerning their appearance and distribution during human odontogenesis and jaw development are available. Methods: Serial sections of decalcified and paraffin-embedded specimens from the jaw regions of human embryos (6th - 22nd gestational week (gw)) were investigated immunohistochemically using mono- and polyclonal antibodies against IGF-II and IGFBP-6. Results: The results mainly showed a colocalization and an increasing intensity of immunoreactivity with gestational age. Immunostaining could already be demonstrated in the dental lamina and later in the enamelum organ. Strong staining appeared in the enamelum knot and Hertwig's epithelial sheeth (HERS). With the beginning of the 10th gw both factors could be localized in dental papilla and follicle. While Meckel's cartilage was unstained, strong reactivity could be seen in the jaw blastema and in osteoblasts. Conclusions: The results show that IGF-II and IGFBP-6 are both involved in orofacial development. Findings in the enamelum knot and HERS indicate a role of IGF-II in proliferation. Its appearance in the developing jaw bones reveals a function in osteogenesis. The colocalization with IGFBP-6 demonstrates biological interaction with its ligand, thus probably controlling mitogenesis.