title: Delayed tooth eruption and suppressed osteoclast number in the eruption pathway of heterozygous Runx2/Cbfa1 knockout mice.
abstract: Genetic studies have recently identified a mutation of one allele of runt-related gene 2 (RUNX2/CBFA1) as the cause for an autosomal-dominant skeletal disorder, cleidocranial dysplasia (CCD), which is characterised by hypoplasia of the clavicles and calvariae and widened sutures and fontanelles. In addition, CCD is frequently affected with multiple supernumerary teeth and the impaction and delayed eruption of teeth, the causes of all these dental abnormalities are still unknown. To clarify the cellular mechanism of the delayed tooth eruption in CCD, the process of tooth eruption was examined in heterozygous Runx2/Cbfa1 (mouse homolog of RUNX2/CBFA1) knockout mice, known to mimic most of the bone abnormalities of CCD. The timing of the appearance of maxillary and mandibular teeth into the oral cavity was significantly delayed in heterozygous mutant mice compared with wild-type mice. From postnatal days 8 to 10, an active alveolar bone resorption and a marked increase of the osteoclast surfaces was observed in the eruption pathway of both genotypes, but this increase was significantly suppressed in the mutant mice. In contrast, the osteoclast surfaces did not show a significant difference between the two genotypes in the future cortical area of femora. These results suggest that haploinsufficiency of Runx2/Cbfa1 does not effect the femoral bone remodelling but is insufficient for the active alveolar bone resorption essential for the prompt timing of tooth eruption. These results also suggest the possibility that impaired recruitment of osteoclasts is one of the cellular mechanisms of delayed tooth eruption in CCD patients.
authors.affiliation: Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yoda
authors.forename: Naoto
authors.initials: N
authors.lastname: Suda
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kitahara
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Komori
authors.forename: Kimie
authors.initials: K
authors.lastname: Ohyama
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000235:genetics; D002973:Cleidocranial Dysplasia / Q000235:genetics* / Q000473:pathology; D050659:Core Binding Factor Alpha 1 Subunit; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010010:Osteoclasts / Q000502:physiology*; D014078:Tooth Eruption / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; D014157:Transcription Factors