title: Functional role of Rho-kinase in ameloblast differentiation.
abstract: During tooth development, inner enamel epithelial (IEE) cells differentiate into enamel-secreting ameloblasts, a polarized and elongated cellular population. The molecular underpinnings of this morphogenesis and cytodifferentiation, however, are not well understood. Here, we show that Rho-associated coiled-coil-containing protein kinase (ROCK) regulates ameloblast differentiation and enamel formation. In mouse incisor organ cultures, inhibition of ROCK, hindered IEE cell elongation and disrupted polarization of differentiated ameloblasts. Expression of enamel matrix proteins, such as amelogenin and ameloblastin, and formation of the terminal band structure of actin and E-cadherin were also perturbed. Cultures of dental epithelial cells revealed that ROCK regulates cell morphology and cell adhesion through localization of actin bundles, E-cadherin, and β-catenin to cell membranes. Moreover, inhibition of ROCK promoted cell proliferation. Small interfering RNA specific for ROCK1 and ROCK2 demonstrated that the ROCK isoforms performed complementary functions in the regulation of actin organization and E-cadherin-mediated cell-cell adhesion. Thus, our results have uncovered a novel role for ROCK in amelogenesis.
authors.affiliation: The Advanced Oral Health Science Research Center, Iwate Medical University, Iwate, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Otsu
authors.forename: Ryota
authors.initials: R
authors.lastname: Kishigami
authors.forename: Naoki
authors.initials: N
authors.lastname: Fujiwara
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Ishizeki
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Harada
mesh_terms: D000565:Ameloblasts / Q000166:cytology / Q000201:enzymology*; D000566:Amelogenesis / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D007180:Incisor / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D051379:Mice; D009924:Organ Culture Techniques; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
chemical_list: D047428:Protein Kinase Inhibitors; C515854:Rock1 protein, mouse; C515855:Rock2 protein, mouse; D054460:rho-Associated Kinases