title: Role of RANKL (TNFSF11)-dependent osteopetrosis in the dental phenotype of Msx2 null mutant mice.
abstract: The MSX2 homeoprotein is implicated in all aspects of craniofacial skeletal development. During postnatal growth, MSX2 is expressed in all cells involved in mineralized tissue formation and plays a role in their differentiation and function. Msx2 null (Msx2 (-/-)) mice display complex craniofacial skeleton abnormalities with bone and tooth defects. A moderate form osteopetrotic phenotype is observed, along with decreased expression of RANKL (TNFSF11), the main osteoclast-differentiating factor. In order to elucidate the role of such an osteopetrosis in the Msx2 (-/-) mouse dental phenotype, a bone resorption rescue was performed by mating Msx2 (-/-) mice with a transgenic mouse line overexpressing Rank (Tnfrsf11a). Msx2 (-/-) Rank(Tg) mice had significant improvement in the molar phenotype, while incisor epithelium defects were exacerbated in the enamel area, with formation of massive osteolytic tumors. Although compensation for RANKL loss of function could have potential as a therapy for osteopetrosis, but in Msx2 (-/-) mice, this approach via RANK overexpression in monocyte-derived lineages, amplified latent epithelial tumor development in the peculiar continuously growing incisor.
authors.affiliation: INSERM, UMR 872, Centre de Recherche des Cordeliers, Laboratoire de Physiopathologie Orale Moléculaire, Equipe 5, Paris, F-75006 France; Université Paris-5, Paris, F-75006; Université Paris-6, Paris, F-75006 France; Université Paris-7, Paris, F-75006 France ; Department of Basic Studies, Faculty of Odontology, University of Antioquia, Medellin, Colombia.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Castaneda
authors.forename: Yohann
authors.initials: Y
authors.lastname: Simon
authors.forename: Didier
authors.initials: D
authors.lastname: Ferbus
authors.forename: Benoit
authors.initials: B
authors.lastname: Robert
authors.forename: Julie
authors.initials: J
authors.lastname: Chesneau
authors.forename: Christopher
authors.initials: C
authors.lastname: Mueller
authors.forename: Ariane
authors.initials: A
authors.lastname: Berdal
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lézot
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010022:Osteopetrosis / Q000503:physiopathology*; D010641:Phenotype; D053245:RANK Ligand / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014070:Tooth; D055114:X-Ray Microtomography
chemical_list: D017931:DNA Primers; D018398:Homeodomain Proteins; C084119:MSX2 protein; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse