title: The receptor activator of nuclear factor-kappa B ligand-mediated osteoclastogenic pathway is elevated in amelogenin-null mice.
abstract: Amelogenins, major components of developing enamel, are predominantly involved in the formation of tooth enamel. Although amelogenins are also implicated in cementogenesis, their precise spatial expression pattern and molecular role are not clearly understood. Here, we report for the first time the expression of two alternate splice forms of amelogenins, M180 and the leucine-rich amelogenin peptide (LRAP), in the periodontal region of mouse tooth roots. Lack of M180 and LRAP mRNA expression correlated with cementum defects observed in the amelogenin-null mice. The cementum defects were characterized by an increased presence of multinucleated cells, osteoclasts, and cementicles. These defects were associated with an increased expression of the receptor activator of the nuclear factor-kappa B ligand (RANKL), a critical regulator of osteoclastogenesis. These findings indicate that the amelogenin splice variants, M180 and LRAP, are critical in preventing abnormal resorption of cementum.
authors.affiliation: Functional Genomics Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Junko
authors.initials: J
authors.lastname: Hatakeyama
authors.forename: Taduru
authors.initials: T
authors.lastname: Sreenath
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hatakeyama
authors.forename: Tamizchelvi
authors.initials: T
authors.lastname: Thyagarajan
authors.forename: Lillian
authors.initials: L
authors.lastname: Shum
authors.forename: Carolyn W
authors.initials: CW
authors.lastname: Gibson
authors.forename: J Tim
authors.initials: JT
authors.lastname: Wright
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
mesh_terms: D017398:Alternative Splicing; D053523:Amelogenin; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D017931:DNA Primers; D003739:Dental Cementum / Q000473:pathology*; D003746:Dental Enamel Proteins / Q000172:deficiency* / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008963:Molar / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D053523:Amelogenin; C507200:Amelx protein, mouse; D002352:Carrier Proteins; D017931:DNA Primers; D003746:Dental Enamel Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; C067432:leucine-rich amelogenin peptide