title: The glycogen metabolism via Akt signaling is important for the secretion of enamel matrix in tooth development.
abstract: Cells alter their energy metabolism depending on the stage of differentiation or various environments. In the ameloblast differentiation of continuous growing mouse incisors, we found temporary glycogen storage in preameloblasts before the start of enamel matrix secretion and investigated the relationship between enamel matrix secretion and glycogen metabolism. Immunohistochemistry showed that in the transitional stage from preameloblasts to secretory ameloblasts, the glycogen synthase changed from the inactive form to the active form, the expression of glycogen phosphorylase increased, and further, the levels of IGF-1, IGF-1 receptor and activated Akt increased. These results suggested that the activation of Akt signaling via IGF is linked to the onset of both glycogen metabolism and enamel matrix deposition. In the experiments using organ culture and ameloblast cell line, the activation of Akt signaling by IGF-1 stimulated glycogen metabolism through the up-regulation of Glut-1,-4 and Gsk-3β and the dephosphorylation of glycogen synthase. Subsequently, they resulted in increased enamel matrix secretion. In contrast, some inhibitors of Akt signals and glycogen synthesis/degradation down-regulated enamel matrix secretion. Taking these findings together, glycogen metabolism via Akt signaling is an essential system for the secretion of enamel matrix in ameloblast differentiation.
authors.affiliation: Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan. Electronic address: hyone@dent.niigata-u.ac.jp.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ida-Yonemochi
authors.affiliation: Division of Developmental Biology and Regenerative Medicine, Department of Anatomy, Iwate Medical University, 2-1-1, Nishitokuda, Yahaba, Shiwa-gun, Iwate 028-3694, Japan. Electronic address: kotsu@iwate-med.ac.jp.
authors.forename: Keishi
authors.initials: K
authors.lastname: Otsu
authors.affiliation: Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan. Electronic address: histoman@dent.niigata-u.ac.jp.
authors.forename: Hayato
authors.initials: H
authors.lastname: Ohshima
authors.affiliation: Division of Developmental Biology and Regenerative Medicine, Department of Anatomy, Iwate Medical University, 2-1-1, Nishitokuda, Yahaba, Shiwa-gun, Iwate 028-3694, Japan. Electronic address: hideha@iwate-med.ac.jp.
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Harada
mesh_terms: D000566:Amelogenesis; D000818:Animals; D002460:Cell Line; D003743:Dental Enamel / Q000254:growth & development / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D007180:Incisor / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D008813:Mice, Inbred ICR; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D013002:Somatomedins / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D013002:Somatomedins; D006003:Glycogen; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt signaling; Ameloblast; Cell differentiation; Glycogen; Glycogen metabolism; IGF-1